Trial Outcomes & Findings for Treatment Study of Carnosine Versus Placebo in Gulf War Illness (GWI) (NCT NCT00810368)

NCT ID: NCT00810368

Last Updated: 2019-06-28

Results Overview

CFS Severity Score (Δ ≥ 5 / 36) (Baraniuk et al., 1998; Baraniuk et al., 2000a; Baraniuk, Naranch, Maibach, \& Clauw, 2000b). Subjects scored the severity of the 9 CFS criteria (Fatigue, memory/concentration, sore throat, sore lymph nodes, sore muscles, sore joints, headache, sleep disturbances, exertional exhaustion from Fukuda et al. 1994) on a scale of none (score=0), trivial (1), mild (2), moderate (3) and severe (4). The sum was 36. Individuals taking carnosine were predicted to show a decrease of ≥ 5 at week 12 compared to week 0, compared to no change for placebo subjects. 2-tailed paired t-tests were used to determine significant incremental changes for individuals in the carnosine group compared to the placebo group.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

Weeks 0 and 12

Results posted on

2019-06-28

Participant Flow

Participant milestones

Participant milestones
Measure
Carnosine Treatment Group
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Overall Study
STARTED
18
15
Overall Study
COMPLETED
12
13
Overall Study
NOT COMPLETED
6
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Carnosine Treatment Group
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Overall Study
Lost to Follow-up
4
2
Overall Study
Lack of Efficacy
2
0

Baseline Characteristics

Treatment Study of Carnosine Versus Placebo in Gulf War Illness (GWI)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Carnosine Treatment Group
n=18 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
n=15 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Total
n=33 Participants
Total of all reporting groups
Age, Continuous
51.8 years
STANDARD_DEVIATION 11.6 • n=5 Participants
47.2 years
STANDARD_DEVIATION 8.7 • n=7 Participants
49.5 years
STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male
Female
4 Participants
n=5 Participants
5 Participants
n=7 Participants
9 Participants
n=5 Participants
Sex: Female, Male
Male
14 Participants
n=5 Participants
10 Participants
n=7 Participants
24 Participants
n=5 Participants
Region of Enrollment
United States
18 participants
n=5 Participants
15 participants
n=7 Participants
33 participants
n=5 Participants

PRIMARY outcome

Timeframe: Weeks 0 and 12

Population: Significant numbers of subjects dropped out of both arms of the study. The primary reason given was perceived lack of efficacy.

CFS Severity Score (Δ ≥ 5 / 36) (Baraniuk et al., 1998; Baraniuk et al., 2000a; Baraniuk, Naranch, Maibach, \& Clauw, 2000b). Subjects scored the severity of the 9 CFS criteria (Fatigue, memory/concentration, sore throat, sore lymph nodes, sore muscles, sore joints, headache, sleep disturbances, exertional exhaustion from Fukuda et al. 1994) on a scale of none (score=0), trivial (1), mild (2), moderate (3) and severe (4). The sum was 36. Individuals taking carnosine were predicted to show a decrease of ≥ 5 at week 12 compared to week 0, compared to no change for placebo subjects. 2-tailed paired t-tests were used to determine significant incremental changes for individuals in the carnosine group compared to the placebo group.

Outcome measures

Outcome measures
Measure
Carnosine Treatment Group
n=12 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
n=13 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Effect of Carnosine Supplementation on Chronic Fatigue Syndrome Severity Scores
-3.8 units on a scale
Interval -11.1 to 3.5
-2.0 units on a scale
Interval -8.4 to 4.4

PRIMARY outcome

Timeframe: Weeks 0 and 12

Population: Participants with evaluable data at the end of the study.

Patients were given questionnaires assessing common symptom complaints of diarrhea.

Outcome measures

Outcome measures
Measure
Carnosine Treatment Group
n=7 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
n=10 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Subjects With Improved Diarrhea Symptoms
5 participants
1 participants

PRIMARY outcome

Timeframe: Week 0 and Week 12

Population: Number of participants with evaluable data who completed the study

Instantaneous Fatigue was scored as none (0) to severe (10) at week 0 and week 12. The difference between the Week 12 minus the Week 0 values was the incremental change. If the incremental change was greater than 0, then the Instantaneous Fatigue was worse at week 12 than week 0. If the incremental change was less than 0, then the Instantaneous Fatigue was improved at week 12 compared to week 0. The total potential range for incremental change was from -10 to +10.

Outcome measures

Outcome measures
Measure
Carnosine Treatment Group
n=7 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
n=12 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Incremental Change in Fatigue Score From Baseline to Week 12
0.3 units on a scale
Interval -0.7 to 1.3
-0.6 units on a scale
Interval -2.4 to 1.2

PRIMARY outcome

Timeframe: Week 0 and Week 12

Population: Number of participants with evaluable data who completed the study

Incremental change in Medical Outcome Survey Short Form 36 questionnaire (SF36) Bodily Pain score from baseline to week 12. The Medical Outcome Survey Short Form 36 questionnaire (SF36) Bodily Pain score ranges from 0 (very bad bodily pain) to 100 (no bodily pain). The incremental change was the Medical Outcome Survey Short Form 36 questionnaire (SF36) Bodily Pain score at week 12 minus the Medical Outcome Survey Short Form 36 questionnaire (SF36) Bodily Pain score at baseline. The range of scores for incremental change was from -100 to +100. Scores of 0 for Medical Outcome Survey Short Form 36 questionnaire (SF36) Bodily Pain score at baseline and +100 at week 12 indicate an incremental change of 100 - 0 = +100. A score of 100 at baseline for the Medical Outcome Survey Short Form 36 questionnaire (SF36) Bodily Pain score at baseline of +100 at week 12 gives an incremental change of 0 - 100 = -100.

Outcome measures

Outcome measures
Measure
Carnosine Treatment Group
n=8 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
n=10 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
SF36 Bodily Pain
5.6 units on a scale
Interval -6.4 to 17.6
-0.5 units on a scale
Interval -13.4 to 12.4

PRIMARY outcome

Timeframe: Week 0 and Week 12

Population: Number of participants with evaluable data who completed the study

Each item on the Generalized Anxiety Scale (GAD) scores was scored as none (0), trivial (1), mild (2), moderate (3), or severe (4) and the sum of the 7 items calculated (range 0 to 28). The incremental change between Week 0 and Week 12 was determined for each treatment.

Outcome measures

Outcome measures
Measure
Carnosine Treatment Group
n=8 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
n=9 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Incremental Change in Generalized Anxiety Scale (GAD) Scores From Baseline to Week 12
0.2 units on a scale
Interval -2.3 to 2.7
-0.9 units on a scale
Interval -4.1 to 2.3

PRIMARY outcome

Timeframe: Week 0 and Week 12

Population: Number of participants with evaluable data who completed the study

Incremental change in SF36 General Health score from baseline to week 12. The SF36 General Health score ranges from 0 (very bad General Health) to 100 (very good General Health). The incremental change was the SF36 General Health score at week 12 minus the SF36 General Health score at baseline. The range of scores for incremental change was from -100 to +100. Scores of 0 for SF36 General Health score at baseline and +100 at week 12 indicate an incremental change of 100 - 0 = +100. A score of 100 at baseline for the SF36 General Health score at baseline of +100 at week 12 gives an incremental change of 0 - 100 = -100.

Outcome measures

Outcome measures
Measure
Carnosine Treatment Group
n=8 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
n=10 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Incremental Change in SF36 General Health Between Baseline and Week 12
0.5 units on a scale
Interval -13.3 to 14.3
6.5 units on a scale
Interval -4.3 to 17.3

SECONDARY outcome

Timeframe: Difference between Week 0 and Week 12 (end of study)

Population: 2 carnosine subjects had incomplete data.

Digit Symbol Substitution (WAIS) test (Joy et al., 2000): Subjects were given a table of numerals with matching symbols, and a form with random numerals with open spaces. The objective was to write in as many symbols that corresponded to the random numerals within a 90 second period. Each subject was their own control. The outcome measure was the incremental change in this score between Week 0 and Week 12 (units on a scale). Higher scores indicate better performance.

Outcome measures

Outcome measures
Measure
Carnosine Treatment Group
n=10 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
n=13 Participants
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Digit Symbol Substitution (WAIS)
10.8 units on a scale
Interval 6.0 to 15.6
2.7 units on a scale
Interval -0.9 to 6.3

Adverse Events

Carnosine Treatment Group

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Placebo Control Group

Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Carnosine Treatment Group
n=12 participants at risk
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
n=13 participants at risk
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Immune system disorders
Elevated CRP Levels
0.00%
0/12 • 12 weeks
7.7%
1/13 • 12 weeks

Other adverse events

Other adverse events
Measure
Carnosine Treatment Group
n=12 participants at risk
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Carnosine. Veterans who meet GWI criteria will be given 500mg Carnosine x2 daily for 12 weeks.
Placebo Control Group
n=13 participants at risk
A double blinded placebo controlled study. The pharmacy at Georgetown University Medical Center, will blind the Placebo. Controls who are aged and gender match and do not meet GWi and other exclusionary criteria microcrystalline cellulose placebo tablets x2 daily for 12 weeks.
Musculoskeletal and connective tissue disorders
Costochondritis
8.3%
1/12 • Number of events 1 • 12 weeks
0.00%
0/13 • 12 weeks
Blood and lymphatic system disorders
Hypergammaglobulinemia
8.3%
1/12 • Number of events 1 • 12 weeks
0.00%
0/13 • 12 weeks

Additional Information

Dr. James N Baraniuk

Georgetown University Medical Center

Phone: 202-687-8231

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place