Traumatic Brain Injury (TBI)

Mentor: Dr. Emilia Bagiella

Claudy PhilemonThe City College of New York

Danaè WilliamsRutgers University

TBI Incidence & Prevalence in the USA

1.7 million/yr injured (estimated)

1.365 million/yr emergency dept. visits

275,000/yr are hospitalized

52,000/yr die with TBI

Leading cause of death and disability under age 44

M Faul, et al.: CDC, 2010

Zaloshnja E, et al.: J Head Trauma Rehab, 2008

3.2 million living with TBI disability (estimated)

CDC figures

BackgroundObjective:

To determine whether Amantadine Hydrochloride (AH) promotes recovery of

function and consciousness after 4 weeks in TBI patients with disorder of

consciousness (DOC).

Study Design: • Double blind randomized placebo controlled clinical trial

• 184 patients randomized to AH or placebo arm

• Stratified by DOC status (VS vs. MCS) and

time post-injury (28-70 days vs. 71-112 days)

• 4 weeks active treatment and 2 weeks washout period

• Dosage of AH: 200 – 400 mg/day

• 11 multicenter clinical sites

Severe TBI and disorders of consciousness (DOC)

Coma• no eye opening or sleep-wake cycles

Vegetative State (VS)• reemergence of eye opening and sleep-wake cycles

Minimally Conscious State (MCS)• e.g., beginning tracking/ fixation, purposeful motor

behavior, affective responses, inconsistently following commands

Post-traumatic confusional state (PTCS)• capacity to communicate [accurate simple yes/no],

or functional use of objects

Methods:

5

Screening

and Consent

Randomization and Baseline Assessment

4 week

treatment AH or

Placebo

2 week

wash-outend study

Background

• Duration of the study: Total 6 weeks the active (Amantadine) and inactive (placebo) treatments

• 4 weeks for scores of DRS and CRS-R

• 2 weeks for weekly scoring.

• Outcome of Interests: TBI patients’ ages, times of injury, DRS, and

CRS-R.

• Parameter of Interests: Mean ages, times of injury, DRS, and CRS-R

for severe TBI patients

• Type of data: Categorical and Continuous data

Hypothesis Testing

• H0: µ treatment = µ placebo

• H1: µ treatment ≠ µ placebo

µ treatment = population mean of TBI patients randomly assigned

in the Amantadine treatment .

µ placebo = population mean of TBI patients randomly assigned in

the placebo treatment .

Baseline ComparisonsVARIABLE PLACEBO AH P-VALUE

69 (71.13) 64 (73.56) 0.713211 (88.66) 5 (94.25) 0.1789

37.35 ± 15.46 32.31 ± 15.37 0.4390

0.6874

57 (58.76) 57 (65.52) 0.8613

3.90 ± 0.38 3.93 ± 3.30 0.6627

22.24 ± 2.11 21.78 ± 1.98 0.13459.16 ± 4.38 9.61 ± 3.83 0.4672

Male, no(%)Hispanic, no(%)

High School or Lower, no(%)

Race, no(%)

Other 4 (4.12) 4 (4.60)

White 87 (89.69) 73 (83.91)Black 6 (6.19) 10 (11.49)

Age (mean±SD)

Ln(Time of injury) (mean±SD)

Baseline DRS (mean±SD)

Baseline CRS-R (mean±SD)

Results of TBI Patients’ DRS

Baseline 4 Weeks 6 Weeks

22.2

18.317.5

21.8

17.1 16.9

Average Patients' DRS

Placebo AH

Results of TBI Patients’ CRS-R 4

Wee

ks

6 W

eeks

4 W

eeks

6 W

eeks

4 W

eeks

6 W

eeks

4 W

eeks

6 W

eeks

4 W

eeks

6 W

eeks

4 W

eeks

6 W

eeks

CRS-R Visual CRS-R Motor CRS-R Communi-cation

CRS-R Verbal CRS-R Arousal CRS-R Auditory

33%

41%

26%

32%27% 29%

33%

40%

33%38%

31%

38%43% 44%

41%37%

30%35%

38%36%

43% 41% 39% 40%

Percentage of Patients Who Reached CRS-R MilestonePlacebo AH

VARIABLE PLACEBO AH P-VALUE DRS (mean±SD) 18.32±5.249 17.13±5.027 0.1181

CRS-R Motor, no(%) 25 (25.77) 36 (41.38) 0.4912CRS-R

Communications, no(%)

26 (26.80) 26 (29.89) 0.6431

CRS-R Verbal, no(%) 32 (32.99) 33 (37.93) 0.4839

CRS-R Visual, no(%) 32 (32.99) 37 (42.53) 0.1821

CRS-R Auditory, no(%) 30 (30.93) 34 (39.08) 0.2464

CRS-R Arousal, no(%) 30 (30.93) 34 (39.08) 0.2464

Results At 4 Weeks

VARIABLE PLACEBO AH P-VALUE DRS (mean±SD) 17.45 ± 5.939 16.85 ± 5.510 0.4777

CRS-R Motor, no(%) 31 (31.96) 32 (36.78) 0.4912CRS-R

Communications, no(%)

28 (28.87) 30 (34.48) 0.4129

CRS-R Verbal, no(%) 39 (40.21) 31 (35.63) 0.5234

CRS-R Visual, no(%) 40 (41.24) 38 (43.68) 0.7380

CRS-R Auditory, no(%) 37 (38.14) 35 (40.23) 0.7723

CRS-R Arousal, no(%) 37 (38.14) 36 (41.38) 0.6543

Results At 6 Weeks

Adverse Events

• Most Common Adverse Events:• Insomnia• Agitation• Restlessness• Gastrointestinal Problem• Spasticity

• 86% in Placebo group and 79% in AH group experienced adverse events (P-Value = 0.2635)

Conclusion

• AH shows signs of effectiveness if taken continuously.

•After 4 weeks of treatment, patients taking AH improved

more quickly.

•After 2-week washout period, effectiveness of AH

decreased.

Our Experience In TBI Research

•How to conquer SAS

•Difference between VS and MCS

•DRS and CRS-R study methods

•Structure of the study

•BEST Program Experience

Acknowledgements•Mentor: Dr. Emilia Bagiella•BEST Diversity Faculty

•Dr. Melissa Begg•Emma Benn•Helena Chang•Adam Ciarleglio

•Gary Yu•Justine Herrera•Guest Speakers

•BEST Compadres•Friends and family•Dr. Bruce Levin•Dr. Roger Vaughn•Georgia•Carlos

Group by Patient

group Patient's gender

Frequency Expected Percent Row Pct Col Pct Male Female Total

Placebo 69 70.114 37.50 71.13 51.88

28 26.886 15.22 28.87 54.90

97

52.72

AH 64 62.886 34.78 73.56 48.12

23 24.114 12.50 26.44 45.10

87

47.28

Total 133 72.28

51 27.72

184 100.00

Group by Patients

group Patient's ethnicity

Frequency Expected Percent Row Pct Col Pct

Non-Hispanic and

non-Latino

Hispanic or

Latino Total

Placebo 86 88.565 46.74 88.66 51.19

11 8.4348

5.98 11.34 68.75

97

52.72

AH 82 79.435 44.57 94.25 48.81

5 7.5652

2.72 5.75

31.25

87

47.28

Total 168 91.30

16 8.70

184 100.00

Group by Patients

group Patient's race

Frequency Expected Percent Row Pct Col Pct Asian

Black or African

American White Other

race Total

Placebo 1 1.0543

0.54 1.03

50.00

6 8.4348

3.26 6.19

37.50

87 84.348 47.28 89.69 54.38

3 3.163

1.63 3.09

50.00

97

52.72

AH

1 0.9457

0.54 1.15

50.00

10 7.5652

5.43 11.49 62.50

73 75.652 39.67 83.91 45.63

3 2.837

1.63 3.45

50.00

87

47.28

Total 2 1.09

16 8.70

160 86.96

6 3.26

184 100.00

0

5

10

15

20

25

Per

cent

Plac

ebo

3.3 3.5 3.7 3.9 4.1 4.3 4.5 4.7

0

5

10

15

20

25

Per

cent

AH

lntime_injury

grou

p

0

5

10

15

20

25

30

35

40

Per

cent

Plac

ebo

17.25 18.75 20.25 21.75 23.25 24.75 26.25 27.75

0

5

10

15

20

25

30

35

40

Per

cent

AH

Total DRS score

grou

p

0

5

10

15

20

25

30P

erce

nt

Plac

ebo

1.25 3.75 6.25 8.75 11.25 13.75 16.25 18.75 21.25

0

5

10

15

20

25

30

Per

cent

AH

Total CRS-R Score

grou

p

05

1015202530

Perc

ent

Plac

ebo

15 21 27 33 39 45 51 57 6305

1015202530

Perc

ent

AH

age

Gro

up