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CHAPTER 9

Treatment of Mechanical Low Back Pain with

Static Magnetic Fields: Results of a Clinical

Trial and Implications for Study Design

Robert R. Holcomb, Michael J. McLean, Stefan Engstrm

Diane Williams, Jenna Morey and Barbara McCullough

Vanderbilt University, Nashville, TN [RRH,MJM,SE]

Holcomb International [RRH,JM,BM]

Clin Trials, Research Triangle Park, NC [DW]

9.1. Introduction

The idea of using magnetic devices for the treatment of pain is not new.

Chinese and Incan civilizations used lodestones (naturally occurring mag-

netite) for a variety of ailments. The use of magnetic devices in the Orient

continues to this day in China, Korea and Japan. The Austrian physician

Franz Mesmer, treated individuals with lodestones and subsequently de-

veloped the concept of animal magnetism. Cult-like practices evolved inwhich he would extend his hands over groups of people and treat their

problems, often psychological, with this so-called force (Crabtree 1993).

A committee commissioned by the French Academy of Sciences discred-

ited Mesmer in 1815. From that time forward, there was little mention

of the use of magnetic therapies in clinical therapeutics. However, a text-

book of medicine published in Philadelphia by two physicians (Stokes &

Bell 1842) included descriptions of the use of magnets to treat pain. In the

second volume there is a chapter in which a farmer with shoulder pain wastreated with an anvil-sized magnet. The magnet was hoisted with a rope

through a pulley attached to a ceiling beam. It was then lowered into close

proximity of the painful shoulder. The authors described the relief of the

farmer who felt as if he had been touched by wind.

The advent of magnetic resonance imaging (MRI) in the 1980s provided

evidence that externally imposed magnetic fields can interact with human

tissues in a way that allows them to be imaged. The technique depends on

171

Reprinted from "Magnetotherapy: Potential Therapeutic Benefits and Adverse Effects"MJ McLean, S Engstrm, and RR Holcomb (eds.) Published by The Floating Gallery, NY (2003)


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172 9. ROBERT HOLCOMB ET AL.

the capability of the imposed, strong magnetic field to very slightly change

the overall direction of the spin of protons in the tissue. After perturbing

these protons with radio frequency fields, they realign with the emission

of energy that can be detected, determining the spatial characteristics thatallow physiological imaging. Magnetic fields are now used routinely for

diagnosis in medicine. In contrast, our work concerns therapeutic appli-

cations of magnetic fields, especially using portable skin-attached devices

containing permanent magnets. Special challenges face those who try to

evaluate the clinical benefit of magnetic fields. In this chapter, we will

outline major issues in study design and the implications for future stud-

ies. We will also describe successful trials of therapeutic magnetic devices

against mechanical low back pain. As more is learned about how to studymagnetic field effects, it is clear that many aspects of clinical trial design

must be specially optimized for the study of magnetic devices.

9.2. The Study of Pain

Because of its subjective nature, pain is difficult to study. Different indi-

viduals seldom respond to a similar degree to a standardized painful stim-

ulus. The International Association for the Study of Pain (IASP) defines

pain as an unpleasant sensory and emotional experience associated with

actual or potential tissue damage, or described in terms of such damage

(Merskey & Bogduk 1994). Thus pain is by nature subjective and diffi-

cult to quantify (Katz & Melzack 1999). The Visual Analog Scale (VAS)

is a validated and frequently used instrument for assessing pain: The pa-

tient marks, along a 10 cm line, the intensity of his/her pain between no

pain at the left and worst pain imaginable at the right limit of the line.This provides a quantitative assessment of the subjective impression of

pain intensity. The visual analog scales have significant well-documented

limitations (Chapman et al. 1985). A particularly important limitation is

the insensitivity of repeated measurements with a visual analog scale to

detect reductions in pain. Since pain reduction would be an important de-

terminant of therapeutic benefit of a magnetic device, the instruments of

measure limit the possibility of detecting a therapeutic magnetic field ef-

fect. This means that studies of pain must be designed to reduce the impactof inter-individual variability or must be powered by sufficient numbers of

patients to demonstrate a statistically significant therapeutic benefit. Typ-

ically, therapeutic studies with pharmacological agents involve up to 100

patients per arm in order to demonstrate therapeutic significance in the

range of p

0

0010

05. Often these studies involve secondary outcome

measures, such as functional improvement and sleep improvement. There

are definite attempts to objectivize every element of pain assessment, but at


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9.3. UNIQUE ASPECTS OF MAGNETIC THERAPEUTIC DEVICES 173

the same time, what really matters is the patients perception of sustained

improvement by the treatment and that they continue to use it.

9.3. Unique Aspects of Magnetic Therapeutic Devices

9.3.1. Localization and tissue penetration. Studies of the use of

magnetic devices to treat pain differ significantly from studies of analgesic

medications. Pharmacological therapies result from dissolving compounds

throughout the body, where they can interact with multiple tissues at the

pain-generating site, as well as along neural pathways involved in the lo-

calization and perception of pain. Magnetic treatment devices, on the other

hand, are usually placed in close proximity to the pain generator identifiedby the patient by where he or she places a hand or finger.

Nociceptive structural elements may lie near the surface of the skin or sev-

eral centimeters below the skin. To date, there are no implanted, static

magnetic treatment devices, so the devices must be placed at some distance

from the target. To have any chance of therapeutic benefit, the magnetic

field must envelop the nociceptive components of damaged tissues (e.g.

nerve, muscle, bone). The placement, strength and configuration of themagnets and the spatial variation of the magnetic field determine the depth

of penetration into tissue. Thus, not all magnets and not all magnetic fields

should be expected to have therapeutic benefits, just as all pains cannot

be expected to respond to aspirin or other non-steroidal anti-inflammatory

compounds. Also, effective pharmacological therapies depend on dose to

determine the degree of pain relief. In the case of magnetic fields that de-

crease as the inverse cube of the distance (to a model magnetic dipole),

the dose characteristic is determined by the depth of the pain generators intissue and the time of exposure (cf. Figure 9.1).

9.3.2. Field geometry. Magnetic devices we have used have marked

spatial variation in field strength (gradients) that describe the change in

magnetic field over distance. This also may be an important determinant

of the therapeutic benefit of magnetic fields and may play an important

role in determining the effective tissue dose (McLean et al., this volume).

The effective metric is not known, but there are indications that gradients

play a role (Cavopol et al. 1995). In a different formulation, it has also

been shown that in one experimental model, the field alone is not sufficient

to explain variability in biochemical response to varying field exposures

(Engstrm et al. 2002).


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FIGURE 9.1. Field penetration into tissue. The graph shows how

large an area (ordinate) is exposed to a field over a given threshold

value (contours) at a given depth (abscissa) from the surface of the

device used in this study. The unlabeled iso-field lines in the figure

are (top to bottom): 3.0 mT, 10 mT, 30 mT, and 100 mT.

9.3.3. Skin irritation. Another significant problem in the study ofmagnetic devices is skin irritation as a result of application with various

types of tapes or adhesives. In order to improve acceptability of the treat-

ment, skin care is crucial. This requires routine removal of the tape, cleans-

ing with alcohol and soap, rubbing in vitamin oil to reduce irritability, and

sometimes application of adhesive sprays such as Tegaderm R- . Selection

of hypoallergenic tapes is also important and sometimes a trial and error

method must be used to determine which tape is the least irritating for a

given individual. Despite a relatively high incidence of skin irritation (20

30% of patients report this over time), many individuals will succeed in

using these devices for up to 10 years, once they are skilled at skin hy-

giene.

Many commercially available magnets are sold in fitments, or elastic ap-

purtenances. This allows application of the devices to specific body parts

without tape. However in the absence of specifically designed trials, it is

difficult to know whether any claims of therapeutic benefit are due to themagnetic fields produced by these devices or by the support provided by

the elastic fitments. In studies of magnetic devices, it would be important

not to use fitments that can provide benefit by splinting to confound inter-

pretation of the benefit of the magnetic device. Since proximity to the skin

generally is crucial because of the fields rapid decline with distance from

the magnet, it is important that a fitment not use excessive padding on the

treatment side of the device.


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9.4. STUDY DESIGN FOR CLINICAL TRIALS WITH MAGNETIC DEVICES 175

9.3.4. Safety. Although magnetic treatment devices of many designs,

sizes, and shapes are marketed in the United States, there is little evidence

relating to their safety or efficacy. There has been no assessment of long-

term risk of exposure to focally applied magnetic devices. The absence ofreports cannot be taken as proof of safety. Large fields that are encountered

in industrial settings may have long-term and short-term health risks. In a

review by Repacholi & Greenebaum (1999), a statement is made that there

is no known health risk of static magnetic fields less than 3T (a typical

field strength in MRI). The devices used in the current studies are maxi-

mally one tenth that strong and should have significantly less risks because

of their limited area of application in a human body. Many patients have

worn the magnetic devices described here for long periods, both contin-uous and intermittent, under the aegis of IRB-approved study protocols.

Apart from skin irritation, few adverse events have been noted in relation

to the magnetic fields.

There has been one instance in which a patient inadvertently placed the

magnetic device over a pacemaker and this resulted in a cardiac arrhythmia

and brief loss of consciousness. This could be a potentially life threatening

adverse effect and for this reason patients with pacemakers are not allowedin our studies. Effects of magnetic fields on embryonic development are

unknown and for this reason pregnant women are excluded from the stud-

ies. Women who become pregnant during the studies are dropped. This

is despite the fact that the magnetic device may be placed on the wrist at

significant distances from the fetus.

9.4. Study Design for Clinical Trials with Magnetic Devices

Variability of pain and the focal application of a therapeutic magnetic field

with shallow depth of penetration into the pain-producing body tissues are

two major factors limiting success in clinical trials. As a result, every

aspect of study design should be carefully crafted to reduce the impact of

variability and optimize chances of seeing therapeutically relevant benefits

of the magnetic field. We will discuss below how each element of study

design may impact the outcome of the study.

The dearth of data from large, well-designed, placebo-controlled trials

makes it difficult to understand the meaning of both positive and negative

reports at this time. Reports in the medical literature have revealed mixed

benefits. For example, devices with the same basic design produced by the

same company were reported to be effective against painful diabetic neu-

ropathy (Weintraub 1999, see also chapter in this volume) and ineffective

against a variety of back pains (Collacott et al. 2000). In contrast, results

with devices of different designs showed statistical superiority to placebos


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in the treatment of low back pain (Holcomb et al. 1991) and painful trigger

points of post-polio syndrome (Vallbona et al. 1997, see also Hazelwood,

this volume).

At the heart of understanding the discrepancies lies the problem of learninghow to study magnetic devices. Fields produced by these devices can only

be effective in the limited areas to which they penetrate. This approach

differs from the systemic administration of pharmaceuticals that may affect

more than one target along the pain-processing pathway. Non-steroidal

medications do not treat all pains effectively, and magnetic devices should

not be expected to be panaceas. Finding appropriate conditions is the first

step toward the design of discriminating studies. A seemingly obvious

point is that one should have a therapeutic effect to study before launching

a large-scale clinical study. Experience from open study of a device is a

must in order to create a successful study protocol. Even if the goal is exact

replication of another finding, it is imperative to familiarize oneself with

the application of therapeutic magnets and the inherent problems before

undertaking a masked study.

9.4.1. Positioning of the therapeutic device. Magnetic devices areessentially point-and-shoot devices. They generally have very limited

coverage and this makes positioning critical. If the effective portions of

the field fail to envelop structures involved in pain generation, there is no

chance of therapeutic benefit.

Migratory pain, such as trigger points of fibromyalgia, may be treated ef-

fectively initially when the devices are placed right over punctate trigger

points. However, pain may move and reappear at other trigger points

with time. This does not mean that pain relief is not sustained at the sites

of application necessarily, but it makes fibromyalgia particularly difficult

to study longitudinally because the syndrome is defined in large part by the

abrupt appearance of pain at different locations over time.

An important consideration is the size of the magnetic device being ap-

plied. If the device is small relative to the body tissues involved in pain

generation, the chance of significant benefit is small. One way to increase

the chance of benefit is to cover large areas of skin with a single device orto apply multiple devices in the vicinity of painful or tender tissues. The

latter leads to the special consideration of interaction between the fields

produced by the different devices. That is, if the magnetic fields extend

laterally beyond the edges of the device, positioning devices close together

may lead to interactions between their separate fields that could either in-

crease or decrease their therapeutic benefit.


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9.4.2. Nave subjects. For longer studies, it is important that patients

are nave, i.e. they have never been exposed to treatment with magnetic

devices and do not know what to expect. Expectations produce biases that

may affect assessment of pain in the course of the study. The combinationof variables may be sufficient to obscure efficacy that would otherwise be

detectable.

Ulterior motives such as litigation and disability issues may also affect the

ability of the patient to report changes of pain accurately during a blinded

study. It is not ethical to exclude individuals solely on this basis, but care-

ful design of the inclusion and exclusion criteria may lead to rejection of

such subjects on the basis of highly variable pain, or pain outside the range

acceptable for study candidates.

9.4.3. Placebo. Perhaps one of the most significant problems in

studying magnetic devices is the design of appropriate placebos. Mod-

ern scientific method demands the use of an ineffective (placebo) device

in one treatment arm to compare with the active device or pharmaceutical

in another group (Harrington 1997). Such studies are essential to validate

therapeutic benefit of magnetic devices. If such an approach is demandedof pharmaceuticals that are the principal modality of therapeutic interven-

tion in pain, such designs are applicable to the testing and validation of

novel treatment modalities such as magnetic field therapy.

Non-magnetic placebos may be appropriate controls for testing the benefit

of brief application of magnetic devices. They must be identical in ap-

pearance and weight to the active device, otherwise the study subject will

know immediately if he or she is being treated with something different.

This is a particular problem when patients receive devices in a crossover

fashion that entails treatment with an active device and the placebo in any

order. For the blind to be protected, the individual must be observed closely

and/or the devices must be covered by a pad that prevents detection of the

magnetic field produced by the active device. The most significant prob-

lem with non-magnetic placebos, particularly in studies that last for days

or weeks in the absence of close observation, is that the blind may be easily

broken. Once the study subject determines that he or she has the inactivedevice, the validity of the study is irreparably impaired.

The use of magnetic placebos means that the devices produce magnetic

fields. The subject may detect this by usual means, such as bringing it

in to contact with ferromagnetic materials. Thus, they are led to believe

that they are receiving a magnetic treatment. However, such a device for

clinical trials must have been proven in the laboratory, preferably in pilot

studies, to have no detectable treatment benefit. Any efficacy of the field

produced by placebo would detract from the ability to detect efficacy


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FIGURE 9.2 . A propsed magnetic placebo design. A relatively

thick shell of highly permeable material (steel) returns the mag-

netic flux lines, so that only a very small fraction of the magnetic

field produced by the permanent magnet penetrates into the tissue.

of the active device. This means that magnetic placebos must undergo

validation studies before they can be used in studies to test the efficacy

of the magnetic device. Because of this complication, there have been

no magnetic placebos for long-term trials of therapeutic magnets. The

use of magnetic placebos is more like comparing drug doses. Ideally, the

placebo will have lesser field strength, an altered spatial distribution of the

magnetic field, and a more shallow tissue penetration. These devices are

useful for longer studies, in which the patient visits the study personnel

only intermittently.

Development of magnetic placebo requires close coordination between ba-

sic researchers who can measure the magnetic field properties of the dif-

ferent devices and show in cell or animal models that the placebo does

not have effects similar to those of the active device. Only then should

validation studies be conducted comparing magnetic and non-magnetic de-vices in a blinded, acute pain model to determine what, if any, efficacy the

magnetic placebo device might have in comparison with a non-magnetic

device. So far, no studies have been conducted with validated magnetic

placebos. See Figure 9.2 for a suggested design for a magnetic placebo in

which the magnetic field on the treatment side is a factor 50 below that of

the field on the side facing away from the skin when the device is in use.

9.4.4. Appropriate device. It also seems likely that devices may

have to be designed specifically to treat different types of conditions. One

criterion in designing an effective magnetic field, for example, is the depth

of pain generators below the skin surface. Pain generators involved in

painful diabetic neuropathy are likely to be intradermal, whereas those in-

volved in low back pain are likely to lie up to several centimeters below

the skin surface.


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The device must be easily attached to the skin and the subject should be

instructed in skin care to prevent irritation that could lead to drop-outs that

compromise the outcome of the study. The design of the device must allow

it to be placed in critical positions over pain-generating structures, eitheras single devices or as arrays of devices.

Finally, it would be useful if the magnetic device under study had a known

mechanism of action. The devices used in the studies we will describe here

reversibly block action potential firing and protect neurons from swelling

and death as a result of exposure to excitotoxic amino acids. Although

the precise molecular mechanism of these cellular actions is unknown,

effects on soluble enzymes, transmembrane ion channels, and receptor-

coupled enzyme systems all lead to the possibility that proteins within

the cell change conformation in response to magnetic field exposure (see

McLean et al. in this book). These conformational changes may make the

proteins less responsive to stimulation and limit their activity in hyperex-

citable states that might be involved in producing pain, epilepsy, and other

neurological conditions with or without extensive tissue damage.

9.4.5. Study population. The proper selection of subject populationis a very important aspect of study design for trials of pain relief in general,

and clinical magnets in particular.

A balance must be found for the appropriate set of inclusion/exclusion

criteria to use for the study. One must avoid confounders, but participa-

tion requirements can also be so restrictive that it simply is impossible to

recruit the necessary number of subjects. A partial list of criteria to con-

sider for a pain study include: baseline pain level not too low or too high

(Montgomery 1999), delineation of symptoms for inclusion, age group,

possibly confounding medical conditions, previous surgery for the condi-

tion, body weight if field penetration is an issue, use of concomitant med-

ication, psychiatric disorders, clinically unstable, patients with unresolved

litigation, and pregnancy. Two of these topics (baseline pain interval, med-

ication use) are discussed below.

9.4.6. Controlling variability. There are many sources of variabil-ity in a study of the kind considered here. First of all, there is a scatter

in daily pain intensity that is observable by asking patients to score their

own pain multiple times daily for a period of several weeks. Thus, there is

both variation with time of day, for example morning stiffness and pain in

patients with arthritic pains, and activity-dependent exacerbation of pain

later in the day. Pain also may fluctuate on a day-to-day basis, or even

with longer periodicity, depending on the disease activity. For example,


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rheumatoid arthritis pain may flare and subside in an erratic manner de-

pending on supervening illnesses that enhance inflammation. Variability

can also be caused by changes in the type and amount of medication taken.

Changes in symptomatology can also change perception of pain. This canoccur when activity levels vary. In some cases, muscle contraction pain

may be added to low back pain of other etiologies. A way to control for

this is to ask patients not to change their activity levels or lift objects above

a certain weight in the course of the study. Poor sleep is frequently an ex-

acerbant of pains. Patients in chronic pain sleep poorly and are depressed.

They frequently use medications to sleep, and in some cases tricyclic an-

tidepressants. These drugs may have analgesic and adverse effects that can

confound the assessment of pain. The investigator must decide whether to

slowly taper and discontinue these medications prior to the study to achieve

a monotherapy situation during the trial, or whether to optimize the thera-

pies and then keep the drug dose constant for the study. Comorbid states

may also play a role, with pain worsening due to fever, fatigue, or other

factors.

9.4.7. Appropriate syndromes for study: wrist pain. Taking intoconsideration the unique problems of testing magnetic devices and the de-

sign features for appropriate devices described above, we have performed

pilot studies of the benefit of magnetic devices against several targets. As

outlined above, the important factors include the area covered by the mag-

netic field produced by the device and the depth of penetration into the tis-

sue. The critical idea is to reach pain-generating structures with the most

effective regions of the magnetic field.

The simplest situation is to treat a single target with a single device. The

study of carpal tunnel syndrome is amenable to this arrangement. In a pilot

study we examined the effect of magnetic devices on wrist pain (not nec-

essarily carpal tunnel syndrome) reported by seamstresses in a knitwear

plant. Fifty subjects were randomized to receive either a non-magnetic

placebo or an active device. Significant pain relief was observed when the

active device was placed on wrists involved in ballistic movements that

entailed removing sewn cloth from the sewing machines and placing it ina bin at arms length. Treatment of the other wrist on the arm involved

in pushing the cloth through the machine was not effective. In design-

ing further studies in the industrial workplace, it is necessary to observe

asymmetries in the workstation, or in the utilization of hands, resulting in

over-use that produces pain (Dignan et al. 1996).

While wrist pain seems like an ideal syndrome to study, there are reasons

that it may be very complex. For one thing, the pain generation may occur

in tendons, as opposed to nerve compression in the carpal tunnel. Thus,


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the pathophysiology can be a cofounder. The way around this problem is

to select a homogeneous group of patients. Another pitfall is that there are

no well-standardized scales for assessing efficacy in wrist pain, let alone

carpal tunnel syndrome. The symptoms in carpal tunnel may involve sen-sory or motor symptoms and/or pain. Also, there may or may not be slow-

ing across the carpal tunnel, as determined with nerve conduction studies.

Also, there may or not be denervation changes as a result of chronicity

and severity of the nerve compression. This complex situation requires the

evolution of a validated set of scales for determining changes in various

symptoms as a result of treatment. Also, as pointed out above, prolonged

studies require a well-characterized magnetic placebo.

9.4.8. Appropriate syndromes for study: knee pain/low back pain.

We have also studied the effects of magnetic devices in the treatment of

mechanical low back and knee pain. These syndromes can be caused by

a number of etiologies, including alterations of the immune system. The

study of mechanical low back pain requires laboratory testing to eliminate

inflammatory processes and disk herniation syndromes with radiculopathy

in order to homogenize the study group. Because the area involved may

be large and the pain generators may be centimeters below the surface, it

is necessary to use devices with adequate tissue penetration and it is also

necessary to use multiple devices to cover the large area involved. In knee

pain, pain-sensitive tissues include the tendons, synovium, and periosteum.

Inflammatory products can be found in synovial fluid and there may be

neurogenic pain as a result of inflammation. Thus, the pain may be multi-

factorial. In a case of low back pain, the pain generators may include the

intervertebral disk and the intervertebral ligaments, the joints between pos-terior elements of the vertebral body, nerve root irritation in the foramina

because of stenosis or bony changes, and painful muscle spasm. Involve-

ment of nerve roots and/or spinal cord may produce pain that radiates cir-

cumferentially around the flanks into the lower abdomen and genitalia, or

radicular pains that radiate into the buttocks or down the legs. Once again,

patient selection is important in obtaining a homogeneous study popula-

tion and patient selection should be based on careful characterization of

the multiple components of pain and potential multiple pain generators.Otherwise, the study population must be large and stratification by differ-

ent components of pain or pathophysiologies must be considered.

9.4.9. Instruments of measure. Visual analog scales are commonly

used instruments of measure. Their virtues and vices have been outlined

above. In some instances, validated scales are available for use. For exam-

ple, the WOMAC scales have been validated for studies of pain treatment

in patients with arthritis of the knee and hip. In other cases, the scales


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have not been validated and pilot studies would be necessary to validate

the instruments of measure. The primary and secondary outcome mea-

sures should be determined in the context of claims desired for the device.

Many investigators believe that subjective measures of pain should not beused. However, it could be argued that visual analog scales are subjective

and are also subject to all of the factors that we have discussed in the con-

text of variability. The VAS may be filled out with one mindset on one

day of the study, and another mind set on the other. The virtue of a scale

like the WOMAC is that there are multiple assessments for pain and others

for function and quality of life. This has the advantage of looking at the

pain from a number of different ways. It is instructive to examine pain di-

aries of individuals who have been asked to rate their pain multiple timesdaily, both before and during a controlled study. In our own analysis, we

find that the patients who are keeping such diaries are able to discern ben-

efit from the active device over that from the placebo device (Figure 9.3).

Diaries resemble practical clinical methods. When patients return to their

physician, they will choose to continue or discontinue medications or other

interventions based on whether or not they are improved. If they say they

are not improved, dose adjustments or alterations in the regimen are sug-

gested. This may or may not succeed in eliciting patient cooperation in the

patient contract. Thus, we feel that it may be possible that a subjective,

self-reported scale based on frequent pain assessments may actually be de-

signed in a way that could be demonstrably superior to intermittent mea-

sures by examiners with semiquantitative instruments, such as the VAS or

WOMAC (which is itself a series of visual analog scales). Assessments by

study personnel on an intermittent basis may vary in their timing in relation

to activity. For example if the patient comes to the office by walking somedistance, he may actually have pain upon arrival in the physicians office

due to the activity. If for the next visit he comes by car and is dropped

off and rides in the elevator, the pain may be actually less because of the

absence of activity. To control for this, patients must be instructed to keep

their activity level constant as much as possible during the study. A period

of rest in the office, perhaps an hour or more, may allow the reversal of the

activity-dependent discomfort. In studies we have alluded to above, par-

ticularly with rheumatoid arthritics, patients would come and mark VASscales at the same level of pain they marked prior to wearing the devices

of the study. Yet, they said their quality of life and functional capabilities

were increased so much that they did not want to give back their devices

at the end of the study. These subjective factors are rarely accounted for in

simple pain assessment scales.

9.4.10. Statistics. A power analysis is helpful to determine how large

a study population is needed to detect a treatment effect. However, pilot


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FIGURE 9. 3. Twenty-four hour averages of pain diaries for 77 pa-

tients in a low back pain study. Treatment with either active or

placebo device took place in the intervals 23 and 910, respec-

tively.

studies are frequently necessary to determine what size of effect can be

expected, as well as an estimate of the variance in the collected outcome

measures. This information serves as a basis for the power analysis.

Because each individual responds to pain differently and may assess the

effects of pain-relieving devices differently, it is useful to consider each

subject as his or her own baseline control. This assumes that baseline mea-surements are a true representation of their pretreatment pain level, and

that changes from that level can be determined during the blind. It is then

possible to pool patients who have, in essence, been normalized against

their own baseline pain, and to use nonparametric statistics to test the sig-

nificance of any changes. Another approach is simply to determine mean

baseline pains for the parallel groups and test changes from that baseline

mean during the blind with parametric statistics. Both are acceptable. Us-

ing each subjects own baseline for normalization may allow the use of


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smaller study groups because variability is normalized on an individual

basis.

It was mentioned above that subjects with a low baseline pain may have

difficulties detecting an improvement within the natural variation that ac-companies most types of pain. If pain scores are normalized as change

relative to the baseline, the low-baseline group will tend to be emphasized

in the outcome measure. This is probably not desired, and, for this rea-

son, we recommend using absolute improvement over baseline as the basic

measure of efficacy.

9.4.11. Two examples from the Literature. Collacott et al. (2000)

described the inefficacy of one magnetic device in the treatment of me-

chanical low back pain. The magnetic device used in the study was likely

to have a tissue penetration of only several millimeters. Back pain of many

etiologies: muscle spasm, nerve root irritation by intervertebral disks in

which bony calcifications and pressure induced painful circumstances pro-

duced by certain tumors or spinal stenosis, may all result from structures

that lie centimeters below the surface. Thus, the particular device used

may have had no possibility of treating the pain. These factors are likelyto account for the fact that the study failed to show any significant benefit

from the treatment device under study. This is unfortunate, because the

mismatch between the syndrome and device created a situation in which

the device could not be tested, and, therefore, for scientific and ethical

purposes is irrelevant.

Using devices of similar design to those of Collacott et al. (2000), Wein-

traub (this volume) showed reduction of pain in diabetic neuropathy. The

so-called analgesia dolorosa of diabetes is complex. Nerve endings in the

skin are damaged in a way that produces decreased sensation of touch and

joint movement. Spontaneous firing in abnormal patterns at damaged or

regenerating nerve endings within a few millimeters of the skin surface,

however, may result in spontaneous pain. These endings may be hypersen-

sitive to stimulations that result in so-called allodynia, whereby normally

non-painful stimuli become painful. Characteristically, brushing the toes

with a bed sheet produces pain when a patient goes to bed. It would appearthat the magnetic field produced by the device under study was likely to

reach the structures involved in pain generation.

9.5. Clinical Studies of Low Back Pain

Here, we describe the results of a double-blind, placebo-controlled, two-

way crossover study of magnetic therapy for chronic mechanical low back

pain. This study represents an extension of an earlier pilot study in which


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9.5. CLINICAL STUDIES OF LOW BACK PAIN 185

FIGURE

9.4. Placement of treatment devices in the low back painstudy. Panels B and C show the thick foam pad that was used to

prevent subjects form determining whether they were being treated

with the active or the sham/placebo device.

magnetic devices were used to treat mechanical low back pain and knee

pain with statistically significant results (Holcomb et al. 1991). The study

consisted of two 24-hour periods, one week apart, conducted at two clin-

ical research centers. Pain was assessed by study personnel at four time-points after device placement. Patients were treated with both active and

placebo devices in random order. The devices for both groups in this study

consisted of arrays of four permanent magnets of alternating polarity in a

hypoallergenic, plastic case (Magna BlocTM

U.S. patent 5,312,321).

9.5.1. Pilot study. To treat mechanical low back pain in the this pilot

study, seven devices were placed in a standardized pattern over the lum-bosacral region and coccyx (see Figure 9.4). The arrays were then covered

with a thick foam pad to protect the blind. Forty-one of fifty-four subjects

were treated for mechanical low back pain and seventeen had knee pain.

For the group as a whole, pain was reduced significantly more during treat-

ment with the magnetic treatment device than with the placebo p 0 03

and knee pain (34% greater reduction than placebo) responded better than

low back pain (20% greater reduction than placebo). More analgesic med-

ications were taken during the placebo treatment period than during theactive treatment, but the difference was not statistically significant. The

first study was used to plan this second pilot study with two purposes: (1)

to identify elements of study design that require optimization specifically

for the testing of magnetic devices, and, (2) to help design large, placebo-

controlled trials.

These results from the pilot study are notable because a statistically sig-

nificant result was obtained with a relatively small treatment group. The


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relevance of pain relief that was 20 - 34% better than placebo is open to

question. Put another way, is the statistically significant reduction of pain

also biologically significant? Beecher (1955) compared morphine injec-

tion to saline. He found that the placebo effect was greatest in the imme-diate postoperative period. Fifty-two percent of patients had pain relief

after morphine subcutaneously. Forty percent of patients had pain relief

after placebo injection. Placebo accounted for 77% of the pain relief thus

making morphine 23% more effective than placebo. Since morphine is

considered to be a gold standard of pain relief, one might boldly say that

pain relief by some magnetic fields approaches that of morphine.

9.5.2. Clinical study of back pain. Ninety-eight patients were en-tered in a second study of mechanical low back pain designed along the

lines of the first. Placement of the devices was similar, and, once again,

patients were admitted for two 24-hour periods of observation in clini-

cal research centers one week apart. Pain was assessed with VAS and a

numerical rating scale (NRS-11) at 15 minutes, 1 hour, 3 hours, and 24

hours after placement of devices. Once again, the order of exposure to

placebo and active device was randomized. At all four assessments, the

active device was more effective than the placebo device. The difference

was increasingly greater with time and statistically significant at 24 hours

p

0

04; N

77 in the per-protocol analysis), cf. Table 9.1 for details.

A number of individuals were admitted to the study in violation of the

protocol: 14 patients had taken narcotic analgesics within less than two

weeks prior to, or during the study. This led to variable and inaccurate

reporting of pain intensities. It is better to exclude patients who have taken

narcotics within several weeks to a month of randomization into a study ofa magnetic device. Concomitant medications are another issue. If patients

continue their medications, it is possible to quantify changes in the amount

of medication consumed during the study. In this instance, the active de-

vice is an add-on therapy. If concomitant medications are discontinued and

washed out prior to the study, the device will be studied in a monotherapy

application. This choice should be considered carefully in the design of

studies, in order to satisfy the criteria for claims of efficacy of the device.

Secondary measures. The secondary outcome measures collected in

this study appeared to be equally or more sensitive than the primary VAS

scale. The numerical rating scale (NRS-11) measurements were collected

at the same time as the VAS and showed a very simlar response pattern,

consistent with studies that have examined these scales in detail (Bolton &

Wilkinson 1998, Breiviket al. 2000).

The diary data has the drawback of not being a monitored measurement,

but the greater frequency of data collection allows daily variation to be


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9.6. CONCLUSIONS 187

TABLE 9.1. Low back pain study results. Short-term pain score

reduction for MagnaBloc- and Placebo-treated subjects (N 77).

Mean

SD reduction from baseline is recorded. A two-tailed t-

test was used to evaluate the significance of the differences be-

tween the two treatments. VAS=Visual analog scale (0100);

NRS=Numerical response scale (010).

Time after

treatment

MagnaBloc

improvement

Placebo

improvement

p-value

2 tailed

t-test

VAS 15 min 8.5

16.9 7.2

13.8 0.593

1 h 10.9 18.4 9.1 15.0 0.5013 h 17.5

21.1 11.3

16.9 0.046

24 h 22.5

23.4 16.5

18.8 0.083

NRS 15 min 0.82

1.61 0.69

1.22 0.569

1 h 1.18

1.86 0.87

1.23 0.231

3 h 1.88

2.14 1.20

1.44 0.023

24 h 2.28 2.29 1.51 1.79 0.022

averaged out. Additionally, it allows us to follow the recovery back to

baseline after completion of a treatment period on a day-by-day basis. See

Figure 9.3.

9.6. Conclusions

Studies of magnetic devices must be carefully designed to optimize the

likelihood of significant benefit. The study of magnetic devices is not likethe study of pharmaceuticals for reasons outlined above. Pharmaceutical

agents are dissolved throughout the body and can have an impact on not

only pain generators, but also on pain-processing pathways in the periph-

eral and central nervous system. Magnetic therapies are focal and their

effects are primarily aimed at the pain generators without prospect of alter-

ing pain pathways centrally, unless additional devices are placed not only

at the site of pain and tenderness but also along the spinal cord or over the

head. Careful attention to every aspect of study design is necessary in the

testing of magnetic devices. Focal treatment with therapeutic magnetics is

a double-edged sword. One would expect fewer side effects, but the chance

of showing therapeutic benefit is reduced. The field produced by the mag-

netic device under study must be capable of enveloping the pain generator,

or targets along the pain-processing pathway, in order to be testable. If the

field does not penetrate sufficiently in the body tissues, any study is inap-

propriate. When areas of pain and tenderness are large, multiple devices or


18/19


large devices may be necessary for adequate treatmentthe condition to

be treated must be matched with an appropriate device. Only then can the

potential for benefit from magnetic therapy be determined. An appropriate

field threshold for the purpose of understanding penetration depth is stillunknown. The ambient geomagnetic field level can be considered a natural

low-end cut-off point for static field exposure, unless gradient character at

those field levels is a significant determinant for the physical interaction.

In our own experiments described above, we have seen significant efficacy

of static magnetic fields against pain of diverse etiology. These etiologies

include mechanical back and knee pain in placebo-controlled trials, pain of

rheumatoid arthritis in single blinded trials and control of neuropathic pain

in open use. In the devices we have tested, the arrays of four magnets of

alternating polarity satisfy many of the qualities that we have listed above

as necessary for identifying candidate devices. Namely, we have demon-

strated in the laboratory a plausible cellular effect with implicit mecha-

nisms that could be relevant to pain relief (McLean et al. 1995, Cavopol

et al. 1995). We have been able to demonstrate the depth of tissue pen-

etration in excess of 20 mm (Figure 9.1). This is probably sufficient to

reach many of the pain generators involved in the types of pain we havestudied. However, the success of low back pain studies may have been

compromised by the inability of the fields produced by these devices to

reach deeper into body tissues and affect pain generators at different levels.

The critical nature of positioning has been stressed multiple times above.

We have positioned the devices in standard ways for studies, but in open

use, optimization of placement on an individual basis is the rule. Optimal

positioning results in greater success than has been apparent in placebo-

controlled trials in which the protocol does not allow individualization oftreatment.

Claims of efficacy of many devices currently on the market in the United

States are not supported by results from laboratory and clinical testing.

Therefore, their value is uncertain. It behooves investigators to do ev-

erything possible to establish a fundamental basis for the potential use of

such devices and to design appropriate devices for clinical trials. Based on

our own experience, we feel that pursuit of magnetotherapy is warrantedand that available clinical results are promising, but much remains to be

learned.

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