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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Carnosine Versus Placebo Treatment Study in Gulf War Illness (GWI)

Brief Summary: The purpose of this study is to perform a randomized double-blind, placebo-controlled, 12 week study of the effects of carnosine on cognitive, psychometric, autonomic, and muscle strength outcomes in 100 GWI subjects.

Detailed Summary:

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).

  • Effect of Carnosine Supplementation on Chronic Fatigue Syndrome Severity Scores [ Time Frame: Weeks 0 and 12 ]

    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.

  • Subjects With Improved Diarrhea Symptoms [ Time Frame: Weeks 0 and 12 ]
    Patients were given questionnaires assessing common symptom complaints of diarrhea.
  • Incremental Change in Fatigue Score From Baseline to Week 12 [ Time Frame: Week 0 and Week 12 ]
    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 increm

    Original Primary Outcome: Determine if 6 months of oral carnosine 500 mg twice daily has significant, beneficial effects on:(1)activity, 2)cognitive, 3)plasma proteomic outcomes compared to placebo. [ Time Frame: 09/2011 ]

    Current Secondary Outcome: Digit Symbol Substitution (WAIS) [ Time Frame: Difference between Week 0 and Week 12 (end of study) ]

    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.


    Original Secondary Outcome:

    • Determine the safety of carnosine 500 mg twice daily in GWI volunteers. [ Time Frame: 09/2011 ]
    • Determine if responses to carnosine can be stratified according to "long" versus "short" alleles of the CNDP1 gene. CNDP1 degrades carnosine. [ Time Frame: 09/2011 ]
    • Assess longitudinal changes in the placebo group (natural history of symptom variation in GWI). [ Time Frame: 09/2011 ]


    Information By: Georgetown University

    Dates:
    Date Received: December 17, 2008
    Date Started: August 2008
    Date Completion:
    Last Updated: July 8, 2016
    Last Verified: July 2016