- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00810368
Treatment Study of Carnosine Versus Placebo in Gulf War Illness (GWI)
Carnosine Versus Placebo Treatment Study in Gulf War Illness (GWI)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background: Homocarnosine (beta-alanine - gamma-aminobutyric acid) is one of the most abundant dipeptides in the brain. It has important antioxidant properties. Both beta-alanine and GABA are neurotransmitters, suggesting that cleavage of this dipeptide by carnosine dipeptidase 1 (CNDP1) may have important regulatory functions in vivo.
Drug: Homocarnosine is not available. Carnosine (beta-alanine - histidine) is an over-the-counter dietary supplement that shares the antioxidant properties. We proposed that oral carnosine would be absorbed from the gut, cross the blood brain barrier, reduce presumed brain oxidant stress that participated in illness pathology, and improve subject health.
Hypothesis: Carnosine supplementation for 12 weeks by mouth in Gulf War Illness subjects would improve cognitive and other outcomes compared to placebo treatment.
Subjects: Gulf War Illness subjects met 1996 Fukuda criteria for Chronic Multisymptom Illness.
Design: Pilot study. Double blind randomized placebo controlled with comparisons between Week 0 (Baseline, pre-randomization) and Week 12 (end of study) Outcomes: This pilot study included included cognitive testing, magnetic resonance imaging during the 2-back working memory task, self-report of psychometric and other subjective symptoms, tenderness testing by dolormetry, and pain threshold to assess reproducibility in the placebo-treated subjects, and potential treatment effects in the active study drug subjects. The study and each of the outcomes at weeks 0 and 12 are described in detail in the final published paper and in its extensive supplementary on-line materials (Baraniuk JN et al. Glob J Health Sci. 2013 5:69-81. PMID:23618477 PMCID:PMC4209301).
An improvement on accuracy on the 2-back working memory task between 0 and 12 weeks was the primary outcome.
Other evaluations were secondary outcomes.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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District of Columbia
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Washington, District of Columbia, United States, 20007
- Georgetown University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Evidence of military enlistment between August 1, 1990 and July 31, 1991, and deployment for 30 consecutive days to:
- Persian Gulf waters and adjacent land areas,
- Other global locations, or,
- U.S. only. 1990-1991 enlistment status:
- Active duty
- National Guard
- Reserves
Exclusion Criteria:
- HIV/AIDS
- Pregnant Women
- Active Duty Military Personnel
- Children
- Incarceration
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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ACTIVE_COMPARATOR: Carnosine treatment group
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500mg Carnosine x2 daily
Other Names:
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PLACEBO_COMPARATOR: Placebo control group
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Microcrystalline cellulose placebo tablets x2 daily
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effect of Carnosine Supplementation on Chronic Fatigue Syndrome Severity Scores
Time Frame: Weeks 0 and 12
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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. |
Weeks 0 and 12
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Subjects With Improved Diarrhea Symptoms
Time Frame: Weeks 0 and 12
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Patients were given questionnaires assessing common symptom complaints of diarrhea.
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Weeks 0 and 12
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Incremental Change in Fatigue Score From Baseline to Week 12
Time Frame: Week 0 and Week 12
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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.
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Week 0 and Week 12
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SF36 Bodily Pain
Time Frame: Week 0 and Week 12
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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.
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Week 0 and Week 12
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Incremental Change in Generalized Anxiety Scale (GAD) Scores From Baseline to Week 12
Time Frame: Week 0 and Week 12
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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.
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Week 0 and Week 12
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Incremental Change in SF36 General Health Between Baseline and Week 12
Time Frame: Week 0 and Week 12
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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.
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Week 0 and Week 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Digit Symbol Substitution (WAIS)
Time Frame: Difference between Week 0 and Week 12 (end of study)
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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.
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Difference between Week 0 and Week 12 (end of study)
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Gray GC, Reed RJ, Kaiser KS, Smith TC, Gastanaga VM. Self-reported symptoms and medical conditions among 11,868 Gulf War-era veterans: the Seabee Health Study. Am J Epidemiol. 2002 Jun 1;155(11):1033-44. doi: 10.1093/aje/155.11.1033. Erratum In: Am J Epidemiol. 2005 Feb 1;161(3):302.
- Baraniuk JN, Casado B, Maibach H, Clauw DJ, Pannell LK, Hess S S. A Chronic Fatigue Syndrome - related proteome in human cerebrospinal fluid. BMC Neurol. 2005 Dec 1;5:22. doi: 10.1186/1471-2377-5-22.
- Janssen B, Hohenadel D, Brinkkoetter P, Peters V, Rind N, Fischer C, Rychlik I, Cerna M, Romzova M, de Heer E, Baelde H, Bakker SJ, Zirie M, Rondeau E, Mathieson P, Saleem MA, Meyer J, Koppel H, Sauerhoefer S, Bartram CR, Nawroth P, Hammes HP, Yard BA, Zschocke J, van der Woude FJ. Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1. Diabetes. 2005 Aug;54(8):2320-7. doi: 10.2337/diabetes.54.8.2320.
- Chez MG, Buchanan CP, Aimonovitch MC, Becker M, Schaefer K, Black C, Komen J. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol. 2002 Nov;17(11):833-7. doi: 10.1177/08830738020170111501.
- Baraniuk JN, El-Amin S, Corey R, Rayhan R, Timbol C. Carnosine treatment for gulf war illness: a randomized controlled trial. Glob J Health Sci. 2013 Feb 4;5(3):69-81. doi: 10.5539/gjhs.v5n3p69.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2008-068
- USAMRMC PR# W91ZSQ-7149-N602 (OTHER_GRANT: CDMRP, DoD)
- HRPO Log No. A-14542.2 (OTHER: Human Research Protection Office protocol number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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