Clinical trial NCT00810368: Treatment Study of Carnosine Versus Placebo in Gulf War Illness (GWI)
Official title: Carnosine Versus Placebo Treatment Study in Gulf War Illness (GWI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Persian Gulf Syndrome
Keywords: Carnosine
antioxidant
Persian Gulf War
Gulf War Syndrome
GWI
Gulf War Illness
Exercise
Chronic Fatigue
Fibromyalgia
Veterans
Irritable Bowel Syndrome
Migraine headaches
Neuropathy
Multiple Chemical Sensitivity
Lead sponsor: Georgetown University
Sponsor class: OTHER
First posted: 2008-12-18
Enrollment: 33
Sex: ALL
Minimum age (years): 34
Maximum age (years): 82
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Effect of Carnosine Supplementation on Chronic Fatigue Syndrome Severity Scores
timeFrame: Weeks 0 and 12
measure: Subjects With Improved Diarrhea Symptoms
timeFrame: Weeks 0 and 12
measure: Incremental Change in Fatigue Score From Baseline to Week 12
timeFrame: Week 0 and Week 12
measure: SF36 Bodily Pain
timeFrame: Week 0 and Week 12
measure: Incremental Change in Generalized Anxiety Scale (GAD) Scores From Baseline to Week 12
timeFrame: Week 0 and Week 12
measure: Incremental Change in SF36 General Health Between Baseline and Week 12
timeFrame: Week 0 and Week 12
Secondary outcomes:
measure: Digit Symbol Substitution (WAIS)
timeFrame: Difference between Week 0 and Week 12 (end of study)
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
Study officials:
affiliation: Georgetown University
name: James N Baraniuk, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.