Fecal Microbiota Transplant

Success, Challenges,and the FDA

Cheryl Griesbach, RNMayo Clinic in ArizonaFecal Microbiota Transplant Coordinator

Disclosures

The Society of Gastroenterology Nurses and Associates, Inc. is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s (ANCC) Commission on Accreditation.

Disclosure: Relationships with commercial interest organizations whose products are related to program content include:

None

Objectives: Explain the impact of C. difficile on the

U.S. population. Discuss the benefit of FMT in the patient

with refractory, recurrent C. difficile. List obstacles encountered in the

development of an FMT program. Describe the guidelines as determined by

the FDA for FMT. State the proposed applications of FMT for

treatment of various illness and disease.

Fecal Microbiota Transplant What and Why? Origin

Application - Currently approved for the treatment of recurrent Clostridium difficile, refractory to therapy

Highly toxigenic strain of C. diff BI/NAP1/027

FMT

The Forest Analogy

Fecal Microbiota TransplantProgram Development

FMT Program Goals Build a Model FMT Program

Infrastructure Workflow processes Safety and outcome monitoring tools Establish a clinical practice Capacity for research Collaborative model

Current Patient Flow

Identified as appropriate FMT recipient

Donor Identified and screened

Education recipient and donor

Procedure – FMT

Follow-up – Serial Surveillance

Process timeline

Recipient Eligibility Criteria

Refractory Disease – unresponsive to standard therapy

Two or more documented episodes of severe CDI

Recent positive C. Diff assay consistent with recurrence

Presence of diarrhea at least three unformed stools per day

Potential Donor Screening and Eligibility Criteria

Medical History Screening

Social/Lifestyle Screening

Serology and Microbiology Donor Screening

Serology: Stool Studies:HIV I/II Antibody Bacterial Culture – Enteric PathogensHTLV I/II Antibody O&P Ova and ParasitesRPR or Syphilis EIA Cryptosporidium AntigenHepatitis A IgM Microsporidia SmearHepatitis B Surface Antigen C. Difficile Toxin by PCR or EIA Hepatitis B Core Antibody IgG, IgMHepatitis C Antibody

Recipient Education Points

Discontinue Antimicrobial and pro-biotic 24 H Prior to FMT

Bowel Lavage

Colonoscopy / Loperamide 4 mg

Post procedure instructions/positioning /diet

Serial Surveillance

Donor Education

Dietary – recipient food allergies/low residue

Sample Timing - MOM Do not refrigerate Difficulty obtaining sample

Maintain the “Chain of Custody”

“The Dirty Work”

+ +

+

DONOR SAMPLE

PRESERVATIVE FREE NORMAL SALINE ~250-350 ML

HOMOGENIZE TO SLURRY

STRAIN FILL SYRINGES INSTILL

=

The Procedure

Case Study# 1

71 y.o. male Patient was hospitalized for three weeks following

complications from his left femoral bypass – went on to develop MRSA and was treated with multiple antibiotics.

Subsequently developed C. difficile and became critically ill - ICU

FMT was performed and within three days patient was up walking around feeling so much better.

Case # 2

78 year old female Hospitalized for complications following an exp. Lap

for debulking Stage III ovarian cancer Multiple episodes of CDI Leukocytosis WBC-29.2 (day of procedure) Weak, listless, confused, skin was ashen gray FMT into stoma via inserted urinary catheter

Less than 1 week later:Patient was coherent, skin color was pinkWBC’s dropped to 9.3 four days later

FMT Success

MCA ARIZONA: 93 % Success Rates (Oct. 2013)

58 procedures on 53 patients since January 2011 5 repeat pts. Age ranges 21-90 Avg. 62 39 Females 19 Males

National Average: 90-100%

Hurdles and Challenges in FMT

Known versus UnknownDonor

Does it make a difference?

Ease of scheduling with pre-screened anonymous donor

Safety

Maintaining anonymity

Recruitment of Anonymous Donors

We Need You!

Delivery Method

Colonoscope

NG Tube/Nasal Duodenoscopy

Enema

Misc. other methods

Fresh vs. Frozen Stool

Considerations: Product efficacy Storage Equipment –process

Lab preparation time technician cost

Re-education and continued education is the key

Providers – Mindful prescribing

Patients – Educate your patients about viral vs. bacterial infections.

UTI’s - make sure a culture and sensitivity is done

Over RX of Antimicrobials

Post FMT Stool Testing ?

If it ain’t broke don’t fix it……..

Certain individuals can be colonized

May be helpful in IBD patients

Is Metronidazole the optimal first line therapy?

Should FMT be the first line therapy for C. diff infection?

How do we contain costs and provide this treatment for all patients in need?

How will the new health care changes impact moving forward from here?

Unanswered Questions…….

FMT AND THE FDA

FMT and the FDAMay 3 2013

Fecal Microbiotao When used to cure, treat, mitigate or prevent a

disease fecal microbiota for transplantation meets the legal definition of a drug and/or biological product

o If the fecal microbiota are being used to cure, treat, mitigate or prevent a disease or condition it is considered an unapproved new drug for which an Investigational New Drug application (IND) is required.

o Primary objective of IND is to assure the safety and rights of subjects

Potential Long-term Effects of Alterations in the Gut Microbiome

Immune statusNutritional statusBody weight Diabetes risk

Cardiovascular riskAutoimmune statusCognition/moodCancer riskOther?

IND Requirement - Yes then No

Feedback was overwhelming prompting a recant by the FDA for the IND requirement

Modified Statement from the FDA

On June 17th 2013 a statement was issued:

“The agency acknowledges these concerns and intends to exercise enforcement discretion regarding the IND requirements for the use of FMT to treat C. difficile infection not responding to standard therapies provided the treating physician obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products.  Informed consent should include at a minimum, a statement that the use of FMT products to treat C. difficile is investigational and a discussion of its potential risks.

FMTWhat

does the future hold?

GastroenterologyIBD –Ulcerative colitis, CrohnsIBS – Chronic constipation, diarrhea (not c.diff rel.) Motility Nutrition and AbsorptionObesity

NeurologyParkinson's Disease

Chronic Fatigue Syndrome, Autism, Autoimmune disorders….. The list goes on

In SummaryRates of CDI continue to rise and the strains of the bacteria are more resistant and virulent

FMT is a safe and effective treatment for CDI - Success Rates 90-100%

FDA is exercising enforcement discretion regarding the IND requirements for the use of FMT to treat CDI

Patient Safety : Informed consent-Investigational treatment Chain of custody of stool sample Thorough screening of donor

health/diagnostics

It is imperative that we as clinicians continue to forge ahead with research into the possible application of FMT for treatment of other diseases and conditions.