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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
James Baraniuk, MD, Georgetown University
ClinicalTrials.gov Identifier:
NCT00810368
First received: December 17, 2008
Last updated: July 8, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Persian Gulf Syndrome
Drug: Carnosine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Carnosine Versus Placebo Treatment Study in Gulf War Illness (GWI)

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Effect of Carnosine Supplementation on Chronic Fatigue Syndrome Severity Scores [ Time Frame: Weeks 0 and 12 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.

  • SF36 Bodily Pain [ Time Frame: Week 0 and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Incremental Change in Generalized Anxiety Scale (GAD) Scores From Baseline to Week 12 [ Time Frame: Week 0 and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Incremental Change in SF36 General Health Between Baseline and Week 12 [ Time Frame: Week 0 and Week 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Digit Symbol Substitution (WAIS) [ Time Frame: Difference between Week 0 and Week 12 (end of study) ] [ Designated as safety issue: No ]
    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.


Enrollment: 33
Study Start Date: August 2008
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Carnosine treatment group
Carnosine treatment group
Drug: Carnosine
500mg Carnosine x2 daily
Other Name: Pathway Carnosine supplied by Village Green Apothecary
Placebo Comparator: Placebo control group
Placebo control group
Drug: Placebo
Microcrystalline cellulose placebo tablets x2 daily
Other Name: Village Green Apothecary

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

Ages Eligible for Study:   34 Years to 82 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00810368

Locations
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20007
Sponsors and Collaborators
Georgetown University
Investigators
Principal Investigator: James N Baraniuk, MD Georgetown University
  More Information

Additional Information:
Publications:
Responsible Party: James Baraniuk, MD, Professor of Medicine, Georgetown University
ClinicalTrials.gov Identifier: NCT00810368     History of Changes
Other Study ID Numbers: 2008-068  USAMRMC PR# W91ZSQ-7149-N602  HRPO Log No. A-14542.2 
Study First Received: December 17, 2008
Results First Received: March 24, 2014
Last Updated: July 8, 2016
Health Authority: United States: Food and Drug Administration
United States: Federal Government
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Georgetown University:
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

Additional relevant MeSH terms:
Syndrome
Persian Gulf Syndrome
Disease
Pathologic Processes
Occupational Diseases

ClinicalTrials.gov processed this record on August 25, 2016