Gulf War SyndromePhase 2/3NCT05675878
Confirmation of Diet as a Treatment for Gulf War Illness
A Phase 2/3 study testing Dietary Intervention in people with Gulf War Syndrome and Gulf War Illness, run by American University at 3 sites in United States.
Trial summary
This clinical trial aims to confirm previous findings from a smaller study which demonstrated significant improvements in all symptoms among veterans with Gulf War Illness after one month on the dietary intervention. Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Gulf War Syndrome, Gulf War Illness
- What is being tested?
- Dietary Intervention
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Mar 2023to 31 Dec 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and Females of all races and ethnicities who are ≤75 yrs of age
- Served in the 1990-1991 Persian Gulf War
- Fulfill both Center for Disease Control (CDC) and Kansas definitions of Gulf War Illness
- Stable medication regimen for ≥1 month and willing to keep medications and supplements stable throughout study participation
Who cannot join
- Recent substance use disorder (past year)
- Unwilling to stop using alcohol, tobacco (including vaping) and/or marijuana; or unwilling to change diet
- Diagnosed seizure disorder or severe asthma requiring past hospitalization
- Currently taking medication which affects glutamatergic or GABAergic neurotransmission (but can work with their physician to wean off of these medications prior to participating)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Boston University
Boston, Massachusetts, 02118
Nova Southeastern University
Fort Lauderdale, Florida, 33314
American University
Washington D.C., District of Columbia, 20016
About this study
This clinical trial aims to confirm previous findings from a smaller study which demonstrated significant improvements in all symptoms among veterans with Gulf War Illness after one month on the dietary intervention. The main objectives of this study are: 1) to confirm previous findings of treatment response to the diet in a larger and more diverse group; 2) to examine how changes in the nervous system may be the reason for improvement; and 3) to identify markers which change in the blood after one month on the diet. Participants will have baseline measures collected and then will be randomized into the intervention or wait-listed control group, which they will follow for one month before being reassessed.
Read the detailed description
The rationale for the proposed research comes from observations from a smaller study which demonstrated profound widespread symptom improvements in veterans with Gulf War Illness (GWI) after one month on the diet. Improvements were noted in every symptom domain and included significant reductions in overall symptom number (with an average of 9 symptoms going away), reduced pain, fatigue, depression, anxiety, and post-traumatic stress disorder (PTSD); and concurrent significant improvements in cognitive function and quality of life. Results also demonstrated that those who improved on the diet had a significant reduction in peripheral inflammation, as compared to those who did not improve on the diet. These benefits have been observed without any negative side effects and the majority of participants continued to follow the diet three months after study completion, suggesting continued improvement and good feasibility. The objectives of this study are: 1) to evaluate whether or not the substantial benefits observed in the recently completed clinical trial hold in a larger group of more diverse veterans with GWI, and 2) to identify blood and/or brain measures which predict improvement on the diet. By recruiting a large group of veterans which are representative of those with GWI, the findings of this research should be applicable to the larger GWI community. The impact of this research could be quite profound, with the diet being a no-risk, low-cost treatment option with no side effects, which allows each individual veteran to take back control of his/her health. There are no direct risks to following the diet since it is a healthy whole-food dietary approach which provides all necessary nutrients. The potential benefits of the diet include improvement in GWI symptoms; improvement in quality of life, potential for improvement in other health markers related to diet (such as obesity, diabetes, cardiovascular disease, high blood pressure) and the possibility of benefit to the larger community. If positive results are confirmed in the proposed study, then the next step would be to teach all Veterans Administration (VA) dietitians how to administer the low glutamate diet so that all veterans have access to it, which should be possible within 1-2 years of the completion of this study.
- Conditions
- Gulf War Syndrome, Gulf War Illness
- Being tested
- Dietary Intervention
- Keywords
- Gulf War Illness, GWI, Gulf War Syndrome, Diet, Treatment
- Medical subject headings
- Persian Gulf Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary InterventionBehavioural
This is a whole food, nutrient-dense diet that aims to remove exposure to specific food additives thought to have negative neurological effects, while also optimizing micronutrient intake.
| Study group | Role | What they receive |
|---|---|---|
| Dietary Intervention Group | Experimental | Subjects will undergo a 2-hour in-depth training via Zoom on how to follow the diet and will receive a binder with helpful information. They will be give the weekend to prepare and then will start the diet the following Monday, and will continue following it for 4 weeks before being reassessed in the lab. Receives: Behavioral: Dietary Intervention |
| Waitlisted Control Group | No intervention | The waitlisted control group will follow their usual diet for one month and then will be reassessed (as a comparator group) before being trained on the dietary intervention which they will then follow for the next month. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Symptom Score
This measure computes the number of symptoms being experienced in this widespread chronic pain condition, and also computes a score based on severity of each symptom. The raw symptom score ranges from 0-32, and the symptom severity score ranges from 0-96, with higher scores indicative of worse outcomes.
Measured: 1-month
Patient Global Impression of Change Scale (PGIC)
The PGIC is a self-report measure of the amount of change experienced from the treatment using a 7-point scale with the following options: very much worse, much worse, a little worse, no change, a little better, much better, very much better.
Measured: 1-month
Secondary outcomes (10)
McGill Pain Questionnaire
This pain measure inquires about types of pain sensation ranked on a scale of 0 to 3, with a total score from 0-45. Higher scores indicate worse pain.
Measured: 1-month
Chalder Fatigue Score
The Chalder Fatigue Scale measures the extent and severity of fatigue. It is a scale with answers to each question based on both bimodal and likert scores, resulting in a total score of 0-11 and 0-33, with higher scores indicating more fatigue.
Measured: 1-month
Veterans RAND 36 Item Health Survey (VR-36)
This is a 36-item survey used to measure health related quality of life, to estimate disease burden and to evaluate disease-specific impact on general and selected populations. The items on the questionnaire correspond to eight principal health domains including general health perceptions, physical functioning, role limitations due to physical and emotional problems, bodily pain, energy-fatigue, social functioning and mental health. This results in physical and mental health component quality of life scores, each scored from 0-100, with higher scores indicating a better quality of life.
Measured: 1-month
Brief Irritability Questionnaire (BITe)
This short questionnaire assesses anger and irritability with 5 questions ranked on a 6-point scale. Higher scores indicate more irritability.
Measured: 1-month
Center for Epidemiological Studies Depression Scale (CES-D)
This is a 20-item measure that asks individuals to rate how often over the past week they experienced symptoms associated with depression, such as restless sleep, poor appetite, and feeling lonely. Response options range from 0 to 3 for each item (0 = Rarely or None of the Time, 1 = Some or Little of the Time, 2 = Moderately or Much of the time, 3 = Most or Almost All the Time). Scores range from 0 to 60, with high scores indicating greater depressive symptoms.
Measured: 1-month
Generalized Anxiety Disorder Scale (GAD-7)
A brief questionnaire with 7 questions which measure generalized anxiety disorder. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of 'not at all', 'several days', 'more than half the days', and 'nearly every day', respectively, and adding together the scores for the seven questions. Total scores range from 0-21, with higher scores indicating more anxiety.
Measured: 1-month
PTSD Checklist for DSM-5 (PCL-5)
The PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. The self-report rating scale is 0-4 for each symptom, reflecting a change from 1-5 in the DSM-IV version. Rating scale descriptors are the same: "Not at all," "A little bit," Moderately," "Quite a bit," and "Extremely." A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items, with higher total scores indicating a higher probability of having PTSD.
Measured: 1-month
Cognitive Testing
Cognitive function will be measured using computerized cognitive testing software and one administered exam in-person. An overall score, called a neurocognitive index, is computed as the average of 5 domain scores, with higher scores equating to better cognitive function.
Measured: 1-month
Dolorimetry
Pain threshold will be measured using a dolorimeter, where pressure is applied to 18 points on the body that are typically tender in widespread chronic pain conditions. The participant will report when pain starts and the kilograms of pressure will be recorded. These will be averaged over the 18 sites, with higher scores indicative of having a higher (better) pain threshold.
Measured: 1-month
Biophotonic scanner
A biophotonic scanner will be used to assess long-term carotenoid intake from the diet. This is a painless test where an infared light is shone through the index finger. This results in a numeric score from 0-800, with a higher score indicative of higher dietary carotenoid intake.
Measured: 1-month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2023
- Study start1 Mar 2023
- Primary completion31 Dec 2025
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gulf War SyndromeStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized to either immediately start the intervention diet or to the wait-listed control group. The intervention group will be trained, and then will follow the diet for one month. The waitlisted controls will follow their normal diet for one month, and then will have the opportunity to be trained on the diet and follow the intervention for one month.
- Masking
- None (open label)
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Lead sponsor
- American University
- Sponsor type
- University, hospital or other
- Collaborators
- Boston University, Massachusetts General Hospital, Georgetown University, Nova Southeastern University
- Responsible party
- Principal investigator, Kathleen Holton, American University
- Investigators
- Kathleen F Holton, PhD, MPH, Principal investigator, American University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05675878
- Sponsor's protocol ID
- 2023-46
- Other IDs
- CDMRP-GW210080
- Status last verified
- Dec 2025
- First submitted
- 16 Dec 2022
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Confirmation of Diet as a Treatment for Gulf War Illness
- ClinicalTrials.gov ID
- NCT05675878
- Acronym / sponsor ID
- 2023-46
- Conditions
- Gulf War Syndrome, Gulf War Illness
- Keywords
- Gulf War Illness, GWI, Gulf War Syndrome, Diet, Treatment
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 111 participants (actual)
- Lead sponsor
- American UniversityUniversity, hospital or other
- Collaborators
- Boston University, Massachusetts General Hospital, Georgetown University, Nova Southeastern University
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 9 Jan 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.
This clinical trial aims to confirm previous findings from a smaller study which demonstrated significant improvements in all symptoms among veterans with Gulf War Illness after one month on the dietary intervention. The main objectives of this study are: 1) to confirm previous findings of treatment response to the diet in a larger and more diverse group; 2) to examine how changes in the nervous system may be the reason for improvement; and 3) to identify markers which change in the blood after one month on the diet. Participants will have baseline measures collected and then will be randomized into the intervention or wait-listed control group, which they will follow for one month before being reassessed.
Detailed description
The rationale for the proposed research comes from observations from a smaller study which demonstrated profound widespread symptom improvements in veterans with Gulf War Illness (GWI) after one month on the diet. Improvements were noted in every symptom domain and included significant reductions in overall symptom number (with an average of 9 symptoms going away), reduced pain, fatigue, depression, anxiety, and post-traumatic stress disorder (PTSD); and concurrent significant improvements in cognitive function and quality of life. Results also demonstrated that those who improved on the diet had a significant reduction in peripheral inflammation, as compared to those who did not improve on the diet. These benefits have been observed without any negative side effects and the majority of participants continued to follow the diet three months after study completion, suggesting continued improvement and good feasibility. The objectives of this study are: 1) to evaluate whether or not the substantial benefits observed in the recently completed clinical trial hold in a larger group of more diverse veterans with GWI, and 2) to identify blood and/or brain measures which predict improvement on the diet. By recruiting a large group of veterans which are representative of those with GWI, the findings of this research should be applicable to the larger GWI community. The impact of this research could be quite profound, with the diet being a no-risk, low-cost treatment option with no side effects, which allows each individual veteran to take back control of his/her health. There are no direct risks to following the diet since it is a healthy whole-food dietary approach which provides all necessary nutrients. The potential benefits of the diet include improvement in GWI symptoms; improvement in quality of life, potential for improvement in other health markers related to diet (such as obesity, diabetes, cardiovascular disease, high blood pressure) and the possibility of benefit to the larger community. If positive results are confirmed in the proposed study, then the next step would be to teach all Veterans Administration (VA) dietitians how to administer the low glutamate diet so that all veterans have access to it, which should be possible within 1-2 years of the completion of this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Subjects will be randomized to either immediately start the intervention diet or to the wait-listed control group. The intervention group will be trained, and then will follow the diet for one month. The waitlisted controls will follow their normal diet for one month, and then will have the opportunity to be trained on the diet and follow the intervention for one month.
| Arm | Type | Receives |
|---|---|---|
| Dietary Intervention Group | Experimental | Behavioral: Dietary InterventionSubjects will undergo a 2-hour in-depth training via Zoom on how to follow the diet and will receive a binder with helpful information. They will be give the weekend to prepare and then will start the diet the following Monday, and will continue following it for 4 weeks before being reassessed in the lab. |
| Waitlisted Control Group | No intervention | –The waitlisted control group will follow their usual diet for one month and then will be reassessed (as a comparator group) before being trained on the dietary intervention which they will then follow for the next month. |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males and Females of all races and ethnicities who are ≤75 yrs of age
- Served in the 1990-1991 Persian Gulf War
- Fulfill both Center for Disease Control (CDC) and Kansas definitions of Gulf War Illness
- Stable medication regimen for ≥1 month and willing to keep medications and supplements stable throughout study participation
Key exclusion criteria (4 listed)
- Recent substance use disorder (past year)
- Unwilling to stop using alcohol, tobacco (including vaping) and/or marijuana; or unwilling to change diet
- Diagnosed seizure disorder or severe asthma requiring past hospitalization
- Currently taking medication which affects glutamatergic or GABAergic neurotransmission (but can work with their physician to wean off of these medications prior to participating)
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 |
|---|---|---|
| Dietary InterventionThis is a whole food, nutrient-dense diet that aims to remove exposure to specific food additives thought to have negative neurological effects, while also optimizing micronutrient intake. | Behavioural | Dietary Intervention Group |
Primary outcome
Total Symptom Score
Time frame: 1-month
This measure computes the number of symptoms being experienced in this widespread chronic pain condition, and also computes a score based on severity of each symptom. The raw symptom score ranges from 0-32, and the symptom severity score ranges from 0-96, with higher scores indicative of worse outcomes.
Patient Global Impression of Change Scale (PGIC)
Time frame: 1-month
The PGIC is a self-report measure of the amount of change experienced from the treatment using a 7-point scale with the following options: very much worse, much worse, a little worse, no change, a little better, much better, very much better.
10 secondary outcomes
McGill Pain Questionnaire
Time frame: 1-month
Chalder Fatigue Score
Time frame: 1-month
Veterans RAND 36 Item Health Survey (VR-36)
Time frame: 1-month
Brief Irritability Questionnaire (BITe)
Time frame: 1-month
Center for Epidemiological Studies Depression Scale (CES-D)
Time frame: 1-month
Generalized Anxiety Disorder Scale (GAD-7)
Time frame: 1-month
PTSD Checklist for DSM-5 (PCL-5)
Time frame: 1-month
Cognitive Testing
Time frame: 1-month
Dolorimetry
Time frame: 1-month
Biophotonic scanner
Time frame: 1-month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
Related trials for Gulf War Syndrome
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Growth Hormone Replacement in Veterans With GWI and AGHD (GWIT)
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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. This study is not recruiting at the moment.
Kathleen F Holton, PhD, MPH principal investigator
American University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dietary Intervention in people with Gulf War Syndrome and Gulf War Illness, run by American University at 3 sites 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 4 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: finished, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Symptom Score (time frame: 1-month). 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 5 Oct 2026.