Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00810368
Recruitment Status : Completed
First Posted : December 18, 2008
Results First Posted : August 18, 2016
Last Update Posted : June 28, 2019
Sponsor:
Information provided by (Responsible Party):
James Baraniuk, MD, Georgetown University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Persian Gulf Syndrome
Interventions Drug: Carnosine
Drug: Placebo
Enrollment 33
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Carnosine Treatment Group Placebo Control Group
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 18 15
Completed 12 13
Not Completed 6 2
Reason Not Completed
Lost to Follow-up             4             2
Lack of Efficacy             2             0
Arm/Group Title Carnosine Treatment Group Placebo Control Group Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 18 15 33
Hide Baseline Analysis Population Description
Prior 2-back working memory scores in Gulf War Illness were an average of 17 out of 35 correct (5=95%CI). Sample size for a 50% increase in 2-back working memory scores was 13 per group. 10% per month drop out rate was predicted so our aim was to have 36 subjects enter the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 15 participants 33 participants
51.8  (11.6) 47.2  (8.7) 49.5  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 15 participants 33 participants
Female
4
  22.2%
5
  33.3%
9
  27.3%
Male
14
  77.8%
10
  66.7%
24
  72.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants 15 participants 33 participants
18 15 33
1.Primary Outcome
Title Effect of Carnosine Supplementation on Chronic Fatigue Syndrome Severity Scores
Hide Description

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.

Time Frame Weeks 0 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Significant numbers of subjects dropped out of both arms of the study. The primary reason given was perceived lack of efficacy.
Arm/Group Title Carnosine Treatment Group Placebo Control Group
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 12 13
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-3.8
(-11.1 to 3.5)
-2.0
(-8.4 to 4.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carnosine Treatment Group
Comments Description of Power Calculation: The planned sample size completing each arm was based on individual incremental improvements in the primary outcomes of : A) CFS Severity Scores (Baraniuk et al., Annals Allergy Astma Immunol, 1998), B) Instantaneous Fatigue (Kim et al. Journal of Rehab Res Dev, 2010), and C) increased accuracy of 4/35 letters for 2 back working memory task (Owen, Human Brain Mapping, 2005).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments 2-tailed paired Student's t-tests between Week 0 and Week 12 responses (above) were anticipated to show significant benefits with carnosine treatment but no change with placebo. There were no corrections for multiple comparisons in the reported data.
Method t-test, 2 sided
Comments Paired t-test
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Control Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Subjects With Improved Diarrhea Symptoms
Hide Description Patients were given questionnaires assessing common symptom complaints of diarrhea.
Time Frame Weeks 0 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with evaluable data at the end of the study.
Arm/Group Title Carnosine Treatment Group Placebo Control Group
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 7 10
Measure Type: Number
Unit of Measure: participants
5 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carnosine Treatment Group, Placebo Control Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments Using Fisher's Exact Test, we determined whether there was a significant difference in the number of participants complaining of IBS symptoms.
Method Fisher Exact
Comments 2 by 2 Fisher's Exact Test
3.Primary Outcome
Title Incremental Change in Fatigue Score From Baseline to Week 12
Hide Description 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.
Time Frame Week 0 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants with evaluable data who completed the study
Arm/Group Title Carnosine Treatment Group Placebo Control Group
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 7 12
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.3
(-0.7 to 1.3)
-0.6
(-2.4 to 1.2)
4.Primary Outcome
Title SF36 Bodily Pain
Hide Description 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.
Time Frame Week 0 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants with evaluable data who completed the study
Arm/Group Title Carnosine Treatment Group Placebo Control Group
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 8 10
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
5.6
(-6.4 to 17.6)
-0.5
(-13.4 to 12.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carnosine Treatment Group, Placebo Control Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Primary Outcome
Title Incremental Change in Generalized Anxiety Scale (GAD) Scores From Baseline to Week 12
Hide Description 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.
Time Frame Week 0 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants with evaluable data who completed the study
Arm/Group Title Carnosine Treatment Group Placebo Control Group
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 8 9
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.2
(-2.3 to 2.7)
-0.9
(-4.1 to 2.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carnosine Treatment Group, Placebo Control Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Primary Outcome
Title Incremental Change in SF36 General Health Between Baseline and Week 12
Hide Description 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.
Time Frame Week 0 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants with evaluable data who completed the study
Arm/Group Title Carnosine Treatment Group Placebo Control Group
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 8 10
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.5
(-13.3 to 14.3)
6.5
(-4.3 to 17.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carnosine Treatment Group, Placebo Control Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title Digit Symbol Substitution (WAIS)
Hide Description 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.
Time Frame Difference between Week 0 and Week 12 (end of study)
Hide Outcome Measure Data
Hide Analysis Population Description
2 carnosine subjects had incomplete data.
Arm/Group Title Carnosine Treatment Group Placebo Control Group
Hide Arm/Group Description:

Carnosine treatment group

Carnosine: 500mg Carnosine x2 daily

Placebo control group

Placebo: Microcrystalline cellulose placebo tablets x2 daily

Overall Number of Participants Analyzed 10 13
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
10.8
(6.0 to 15.6)
2.7
(-0.9 to 6.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carnosine Treatment Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Control Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.60
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame 12 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Carnosine Treatment Group Placebo Control Group
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Carnosine Treatment Group Placebo Control Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Carnosine Treatment Group Placebo Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/12 (0.00%)      1/13 (7.69%)    
Immune system disorders     
Elevated CRP Levels  1 [1]  0/12 (0.00%)  1/13 (7.69%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
[1]
At week 6, one subject showed elevated CRP levels (Grade 1, not related). As per protocol, study drug was discontinued for 2 weeks. Hepatitis A, B, and C serologies were negative, and tests normalized. Study drug was restarted with no sequelae.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Carnosine Treatment Group Placebo Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/12 (16.67%)      0/13 (0.00%)    
Blood and lymphatic system disorders     
Hypergammaglobulinemia  1 [1]  1/12 (8.33%)  1 0/13 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Costochondritis * 1 [2]  1/12 (8.33%)  1 0/13 (0.00%)  0
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.0
[1]
One subject had elevated gamma globulins at week 6 (grade 2 adverse event, not related to study drug). The subjects dropped out of the study and was lost to follow-up.
[2]
A subject with chronic rib pain and tenderness of costochondritis was sent by his primary care physician to a cardiologist. No cardiac pathology was found. This was considered Grade 1, not related.

Small sample sizes. No measure of changes in brain carnosine/homocarnosine/GABA.

Subjective outcomes were insensitive to change. Stool consistency needed better scoring system.

Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. James N Baraniuk
Organization: Georgetown University Medical Center
Phone: 202-687-8231
EMail: baraniuklab@gmail.com
Layout table for additonal information
Responsible Party: James Baraniuk, MD, Georgetown University
ClinicalTrials.gov Identifier: NCT00810368    
Other Study ID Numbers: 2008-068
USAMRMC PR# W91ZSQ-7149-N602 ( Other Grant/Funding Number: CDMRP, DoD )
HRPO Log No. A-14542.2 ( Other Identifier: Human Research Protection Office protocol number )
First Submitted: December 17, 2008
First Posted: December 18, 2008
Results First Submitted: March 24, 2014
Results First Posted: August 18, 2016
Last Update Posted: June 28, 2019