Gulf War IllnessNCT05972291
Mechanisms of Gulf War Illness
A study testing Oral Glutamine in people with Gulf War Illness and Irritable Bowel Syndrome, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Many veterans with Gulf War Illness developed chronic gastrointestinal symptoms during their deployment to the Persian Gulf. The pathophysiologic mechanisms of these chronic gastrointestinal symptoms are not well understood but cause significant morbidity in veterans. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Gulf War Illness, Irritable Bowel Syndrome, Gastrointestinal Symptoms
- What is being tested?
- Oral Glutamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Oct 2023to 30 Sep 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Veterans 18-65 years old with GWI and chronic GI symptoms (abdominal pain, diarrhea, bloating) that started during their deployment in the Persian Gulf
- Veterans 18-65 years old with GWI and chronic GI symptoms (abdominal pain, diarrhea, bloating)
- increased intestinal permeability on the lactulose/mannitol permeability test (ratio >0.07)
- able and willing to cooperate with the study
Who cannot join
- current participation in another research protocol or unable to give informed consent
- women with a positive urine pregnancy test or breastfeeding
- history of inflammatory bowel disease, lactose intolerance and/or celiac sprue
- + hydrogen breath test for bacterial overgrowth
- + anti-endomysial antibody titer
- use of NSAIDs 2 weeks before or during the study
Show all 13Show fewer
- known allergy to glutamine or whey protein
- abdominal surgery except for removal of gallbladder, uterus, or appendix >6 months prior to entry into the study
- Abnormal serum BUN and/or creatinine
- Mannitol recovery out of the normal range of 5-25 U/g
- history of kidney disease
- allergies to monosodium glutamate
- current use of anti-seizure medications
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Memphis VA Medical Center, Memphis, TN
Memphis, Tennessee, 38104-2127
George N Verne, (901) 523-8990 ext. 7571, George.Verne@va.gov
Sue A Theus, PhD, (901) 523-8990, sue.theus@va.gov
About this study
Many veterans with Gulf War Illness developed chronic gastrointestinal symptoms during their deployment to the Persian Gulf. The pathophysiologic mechanisms of these chronic gastrointestinal symptoms are not well understood but cause significant morbidity in veterans. Our proposed studies will provide an innovative and novel treatment trial for chronic gastrointestinal symptoms in veterans with Gulf War Illness that were deployed into war zones. Given that there are currently no specific treatments for these disorders, and that current symptomatic approaches are far from ideal, proof of principle of our trial would be an extremely important advance as it would not only have a beneficial impact on the health of many thousands of our veterans, but also it would substantially reduce the many negative economic effects of this ailment on the VA Health Care System.
Read the detailed description
Since 2001, more than 2.2 million US veterans have served in Operation Enduring Freedom (OEF) in Afghanistan and Operation Iraqi Freedom (OIF) in Iraq. The Gulf Registry of the VA Environmental Epidemiology Service identified the majority of these veterans as having chronic health complaints of undetermined etiology. Among the symptoms most frequently reported by veterans with Gulf War Illness (GWI) were chronic fatigue, frequent or persistent headache, frequent or persistent muscle or joint pain, and gastrointestinal (GI) symptoms. GI symptoms (e.g., diarrhea, bloating, and abdominal pain) reported by these veterans accounted for most complaints. Indeed, up to 33% of veterans with GWI suffer from chronic GI symptoms.
The investigators have shown that veterans with GWI and GI symptoms have increased intestinal permeability that drives GI symptoms (Zhang et al., 2019). Our research group recently completed a clinical trial demonstrating the effectiveness of oral glutamine supplementation in diarrhea-predominant IBS patients with increased intestinal permeability (Zhou et al., 2019). The investigators now have obtained preliminary evidence that oral glutamine supplementation may restore intestinal permeability in veterans with GWI and GI symptoms. Based on these new findings, the investigators hypothesize that oral glutamine supplementation will improve the Symptom Severity Scale and restore intestinal permeability in veterans with GWI and chronic GI symptoms. The investigators propose to conduct a randomized, double-blind, placebo-controlled clinical trial studying oral glutamine supplementation compared to placebo in veterans with GWI and GI symptoms.
The human GI tract is the major site of glutamine utilization in the body. Glutamine is a major energy source for rapidly dividing intestinal mucosal cells of the digestive tract. Glutamine helps to protect the lining of the GI tract. Its depletion results in epithelial atrophy and a subsequent increase in intestinal permeability. Glutamine supplementation has been shown to decrease bacterial translocation and intestinal permeability after intestinal injury. Glutamine supplementation has also been shown to decrease intestinal permeability and improve GI function in patients with Crohn's disease, advanced esophageal cancer, or metastatic cancer undergoing radio chemotherapy. There are no published studies to date to support the use of glutamine for veterans with GWI and chronic GI symptoms.
However, given our published studies, preliminary data demonstrating restoration of intestinal permeability with oral glutamine therapy, and the mechanisms of action of glutamine on the GI tract, research testing whether oral glutamine is an effective therapy in veterans with GWI is needed. Given that there are no effective treatments for these veterans and that current treatment approaches are far from ideal, this proposed clinical trial would be extremely important as it would not only have a beneficial impact on the health of many of our veterans, but also it would substantially reduce the negative economic effects on the VA Health Care System.
- Being tested
- Oral Glutamine, Control Arm
- Keywords
- gastrointestinal, irritable bowel syndrome, glutamine
- Medical subject headings
- Irritable Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral GlutamineDietary supplement
You will receive an unmarked packet with either glutamine or whey protein powder. Once the packet is opened, the powder should be mixed completely with 8 oz of water. You should completely drink this mixture within 10 minutes. You will consume one packet three times a day for 12 weeks. One packet 30 minutes before breakfast, one packet 30 minutes before lunch, and one packet 30 minutes before the evening meal.
Control ArmOther
You will receive an unmarked packet with either glutamine or whey protein powder. Once the packet is opened, the powder should be mixed completely with 8 oz of water. You should completely drink this mixture within 10 minutes. You will consume one packet three times a day for 12 weeks. One packet 30 minutes before breakfast, one packet 30 minutes before lunch, and one packet 30 minutes before the evening meal.
| Study group | Role | What they receive |
|---|---|---|
| Oral Glutamine | Experimental | You will be asked to consume 5 grams of glutamine three times a day for 12 weeks. At week four, you will be asked to return to the CRC to be assessed, and then to return every four weeks until week 12, which will be the conclusion of the study. Receives: Dietary Supplement: Oral Glutamine |
| Whey Protein Powder | Placebo comparator | You will be asked to consume 5 grams of whey protein powder three times a day for 12 weeks. At week four, you will be asked to return to the CRC to be assessed, and then to return every four weeks until week 12, which will be the conclusion of the study. Receives: Other: Control Arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine if oral glutamine supplementation will improve the Symptom Severity Scale in Veterans with GWI and chronic GI Symptoms.
It's anticipated that veterans with GWI and GI symptoms will show a significant reduction, compared to placebo, in their chronic GI symptoms as reflected by their Symptom Severity Scale Score following glutamine therapy. For each participating subject, the Symptom Severity Scale score will be measured at baseline, and at 4, 8, and 12 weeks after the start of treatment. The investigators will have Symptom Severity Scale scores at 5 time points in each group (glutamine, placebo). These will be explored graphically with time course plots. At each time point, for Symptom Severity Scale scores, the investigators will also calculate descriptive statistics including mean and standard deviation, as well as median, median absolute deviation and inter-quartile range if the distribution of data is skewed. Box plots will be used to graphically demonstrate the distribution of Symptom Severity Scale scores at each time point. This will be done for both the glutamine and the placebo groups.
Measured: 3 years
To determine if oral glutamine supplementation will restore intestinal permeability in Veterans with GWI.
Following our recent findings, the investigators expect >75% of veterans will restore normal intestinal permeability, while in the placebo group, this percentage is ~6%. One sample one sided proportion test (PROC FREQ in SAS) will be used to test whether the proportion of restoration is >75% in each treatment group (glutamine supplementation or placebo) and two sample one sided proportion tests (PROC FREQ in SAS) to compare the difference between the two groups. To examine the association between the Symptom Severity Scale Score and restoration of normal intestinal permeability, Pearson's correlations between the Symptom Severity Scale and intestinal permeability will be calculated at baseline, and at 4, 8, and 12 weeks after the start of treatment, for both oral glutamine and placebo groups.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2023
- Study start16 Oct 2023
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gulf War IllnessStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In this study, the investigators will conduct a randomized, double-blind, placebo-controlled clinical trial studying glutamine 5 grams orally three times a day compared to a placebo 5 grams orally three times a day for 12 weeks in 80 Veterans with GWI and GI symptoms. This study will also look at Veterans that have chronic GI symptoms and do not have GWI. The Symptom Severity Scale and intestinal permeability will be measured at baseline, 4, 8, and 12 weeks.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- QiQi Zhou, MD PhD, Principal investigator, Memphis VA Medical Center, Memphis, TNGeorge N Verne, Principal investigator, Memphis VA Medical Center, Memphis, TN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05972291
- Sponsor's protocol ID
- SPLD-006-22F
- Other IDs
- I01CX001477
- Status last verified
- Aug 2026
- First submitted
- 24 Jul 2023
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Gulf War Illness
- ClinicalTrials.gov ID
- NCT05972291
- Acronym / sponsor ID
- SPLD-006-22F
- Keywords
- gastrointestinal, irritable bowel syndrome, glutamine
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 16 Oct 2023 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 2 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Many veterans with Gulf War Illness developed chronic gastrointestinal symptoms during their deployment to the Persian Gulf. The pathophysiologic mechanisms of these chronic gastrointestinal symptoms are not well understood but cause significant morbidity in veterans. Our proposed studies will provide an innovative and novel treatment trial for chronic gastrointestinal symptoms in veterans with Gulf War Illness that were deployed into war zones. Given that there are currently no specific treatments for these disorders, and that current symptomatic approaches are far from ideal, proof of principle of our trial would be an extremely important advance as it would not only have a beneficial impact on the health of many thousands of our veterans, but also it would substantially reduce the many negative economic effects of this ailment on the VA Health Care System.
Detailed description
Since 2001, more than 2.2 million US veterans have served in Operation Enduring Freedom (OEF) in Afghanistan and Operation Iraqi Freedom (OIF) in Iraq. The Gulf Registry of the VA Environmental Epidemiology Service identified the majority of these veterans as having chronic health complaints of undetermined etiology. Among the symptoms most frequently reported by veterans with Gulf War Illness (GWI) were chronic fatigue, frequent or persistent headache, frequent or persistent muscle or joint pain, and gastrointestinal (GI) symptoms. GI symptoms (e.g., diarrhea, bloating, and abdominal pain) reported by these veterans accounted for most complaints. Indeed, up to 33% of veterans with GWI suffer from chronic GI symptoms.
The investigators have shown that veterans with GWI and GI symptoms have increased intestinal permeability that drives GI symptoms (Zhang et al., 2019). Our research group recently completed a clinical trial demonstrating the effectiveness of oral glutamine supplementation in diarrhea-predominant IBS patients with increased intestinal permeability (Zhou et al., 2019). The investigators now have obtained preliminary evidence that oral glutamine supplementation may restore intestinal permeability in veterans with GWI and GI symptoms. Based on these new findings, the investigators hypothesize that oral glutamine supplementation will improve the Symptom Severity Scale and restore intestinal permeability in veterans with GWI and chronic GI symptoms. The investigators propose to conduct a randomized, double-blind, placebo-controlled clinical trial studying oral glutamine supplementation compared to placebo in veterans with GWI and GI symptoms.
The human GI tract is the major site of glutamine utilization in the body. Glutamine is a major energy source for rapidly dividing intestinal mucosal cells of the digestive tract. Glutamine helps to protect the lining of the GI tract. Its depletion results in epithelial atrophy and a subsequent increase in intestinal permeability. Glutamine supplementation has been shown to decrease bacterial translocation and intestinal permeability after intestinal injury. Glutamine supplementation has also been shown to decrease intestinal permeability and improve GI function in patients with Crohn's disease, advanced esophageal cancer, or metastatic cancer undergoing radio chemotherapy. There are no published studies to date to support the use of glutamine for veterans with GWI and chronic GI symptoms.
However, given our published studies, preliminary data demonstrating restoration of intestinal permeability with oral glutamine therapy, and the mechanisms of action of glutamine on the GI tract, research testing whether oral glutamine is an effective therapy in veterans with GWI is needed. Given that there are no effective treatments for these veterans and that current treatment approaches are far from ideal, this proposed clinical trial would be extremely important as it would not only have a beneficial impact on the health of many of our veterans, but also it would substantially reduce the negative economic effects on the VA Health Care System.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- In this study, the investigators will conduct a randomized, double-blind, placebo-controlled clinical trial studying glutamine 5 grams orally three times a day compared to a placebo 5 grams orally three times a day for 12 weeks in 80 Veterans with GWI and GI symptoms. This study will also look at Veterans that have chronic GI symptoms and do not have GWI. The Symptom Severity Scale and intestinal permeability will be measured at baseline, 4, 8, and 12 weeks.
| Arm | Type | Receives |
|---|---|---|
| Oral Glutamine | Experimental | Dietary Supplement: Oral GlutamineYou will be asked to consume 5 grams of glutamine three times a day for 12 weeks. At week four, you will be asked to return to the CRC to be assessed, and then to return every four weeks until week 12, which will be the conclusion of the study. |
| Whey Protein Powder | Placebo comparator | Other: Control ArmYou will be asked to consume 5 grams of whey protein powder three times a day for 12 weeks. At week four, you will be asked to return to the CRC to be assessed, and then to return every four weeks until week 12, which will be the conclusion of the study. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Veterans 18-65 years old with GWI and chronic GI symptoms (abdominal pain, diarrhea, bloating) that started during their deployment in the Persian Gulf
- Veterans 18-65 years old with GWI and chronic GI symptoms (abdominal pain, diarrhea, bloating)
- increased intestinal permeability on the lactulose/mannitol permeability test (ratio >0.07)
- able and willing to cooperate with the study
Key exclusion criteria (13 listed)
- current participation in another research protocol or unable to give informed consent
- women with a positive urine pregnancy test or breastfeeding
- history of inflammatory bowel disease, lactose intolerance and/or celiac sprue
- + hydrogen breath test for bacterial overgrowth
- + anti-endomysial antibody titer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral GlutamineYou will receive an unmarked packet with either glutamine or whey protein powder. Once the packet is opened, the powder should be mixed completely with 8 oz of water. You should completely drink this mixture within 10 minutes. You will consume one packet three times a day for 12 weeks. One packet 30 minutes before breakfast, one packet 30 minutes before lunch, and one packet 30 minutes before the evening meal. | Dietary supplement | Oral Glutamine |
| Control ArmYou will receive an unmarked packet with either glutamine or whey protein powder. Once the packet is opened, the powder should be mixed completely with 8 oz of water. You should completely drink this mixture within 10 minutes. You will consume one packet three times a day for 12 weeks. One packet 30 minutes before breakfast, one packet 30 minutes before lunch, and one packet 30 minutes before the evening meal. | Other | Whey Protein Powder |
Primary outcome
To determine if oral glutamine supplementation will improve the Symptom Severity Scale in Veterans with GWI and chronic GI Symptoms.
Time frame: 3 years
It's anticipated that veterans with GWI and GI symptoms will show a significant reduction, compared to placebo, in their chronic GI symptoms as reflected by their Symptom Severity Scale Score following glutamine therapy. For each participating subject, the Symptom Severity Scale score will be measured at baseline, and at 4, 8, and 12 weeks after the start of treatment. The investigators will have Symptom Severity Scale scores at 5 time points in each group (glutamine, placebo). These will be explored graphically with time course plots. At each time point, for Symptom Severity Scale scores, the investigators will also calculate descriptive statistics including mean and standard deviation, as well as median, median absolute deviation and inter-quartile range if the distribution of data is skewed. Box plots will be used to graphically demonstrate the distribution of Symptom Severity Scale scores at each time point. This will be done for both the glutamine and the placebo groups.
To determine if oral glutamine supplementation will restore intestinal permeability in Veterans with GWI.
Time frame: 3 years
Following our recent findings, the investigators expect >75% of veterans will restore normal intestinal permeability, while in the placebo group, this percentage is ~6%. One sample one sided proportion test (PROC FREQ in SAS) will be used to test whether the proportion of restoration is >75% in each treatment group (glutamine supplementation or placebo) and two sample one sided proportion tests (PROC FREQ in SAS) to compare the difference between the two groups. To examine the association between the Symptom Severity Scale Score and restoration of normal intestinal permeability, Pearson's correlations between the Symptom Severity Scale and intestinal permeability will be calculated at baseline, and at 4, 8, and 12 weeks after the start of treatment, for both oral glutamine and placebo groups.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Individual participant dataSharing planned: No
Related trials for Gulf War Illness
RecruitingObservational study
NIH Investigative Deep Phenotyping Study of Gulf War Veteran Health (Project NIH IN-DEPTH)
Gulf War Illness
RecruitingPhase 2
Ca-Mg Butyrate in Gulf War Illness
Gulf War Illness, Chronic Fatigue
Not yet recruiting
Pycnogenol (French Maritime Pine Bark) for the Treatment of Gulf War Illness
Gulf War Syndrome
RecruitingPhase 1
Clinical Evaluation of Montelukast in Veterans With Gulf War Illness
Gulf War Syndrome
Active, not recruitingObservational study
Cardiovascular and Neurovascular Regulation in GWI
Brain Blood Flow, Neurovascular Control
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
QiQi Zhou, MD PhD principal investigator
Memphis VA Medical Center, Memphis, TN
George N Verne principal investigator
Memphis VA Medical Center, Memphis, TN
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oral Glutamine in people with Gulf War Illness and Irritable Bowel Syndrome, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact George N Verne ((901) 523-8990 ext. 7571, George.Verne@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine if oral glutamine supplementation will improve the Symptom Severity Scale in Veterans with GWI and chronic GI Symptoms. (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.