Gulf War SyndromeGWINCT03342482
Glutamate Neuro-Excitotoxicity in GWI
A study testing Low-glutamate diet in people with Gulf War Syndrome, run by American University at 1 site in United States.
Trial summary
The objective of the proposed research is to examine whether dietary exposure to food additives containing glutamate may be contributing to symptoms in Gulf War Illness (GWI). The rationale for proposed study comes from data in the fibromyalgia field which suggests that reducing the consumption of dietary glutamate… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Gulf War Syndrome
- What is being tested?
- Low-glutamate diet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Nov 2017to 31 Aug 2020
- Phase
- Interventional
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males \& Females
- Served (and was deployed) in the Persian Gulf War
- Fulfill both Kansas and CDC definitions of GWI
- Stable medication regimen for 3 or more months
Who cannot join
- Active Duty Military
- Current substance use disorder
- Unwilling to change diet for 2 months
- Severe asthma requiring past hospitalization
- Seizure disorder
Trial locations and contacts
1 site in 1 country.
United States1 site
American University
Washington D.C., District of Columbia, 20016
About this study
The objective of the proposed research is to examine whether dietary exposure to food additives containing glutamate may be contributing to symptoms in Gulf War Illness (GWI). The rationale for proposed study comes from data in the fibromyalgia field which suggests that reducing the consumption of dietary glutamate can reduce over-excitation in the nervous system, leading to symptom improvement. In prior research, a low-glutamate diet (restricting food additive consumption) was tested in fibromyalgia patients. After one-month on the diet, 84% of patients had >30% of their symptoms go away (with 11 symptoms remitting on average), and 8 subjects had complete remission of all symptoms. Subjects then had a significant return of symptoms upon challenge with monosodium glutamate (MSG) as compared to placebo. Since there is almost complete symptom overlap between fibromyalgia and GWI, it is of utmost importance to test this diet as a low-cost treatment option in GWI patients.
The findings from this research will ultimately be applicable to all GWI patients and potentially to other veterans with a similar symptom profile as well. The ultimate impact of this research could be quite profound, as it has the potential to impact all of the symptoms of GWI, as opposed to being a proposed treatment for only one of the symptoms. This dietary treatment has been shown to dramatically affect symptoms like fatigue, cognitive dysfunction, and pain; and thus, has the potential to dramatically improve quality of life for these individuals. Potential benefits of the treatment are great, and risks are minimal, as the treatment involves shifting the diet to a healthier, whole-food approach.
First, the study will confirm or negate the idea that abnormal glutamate signaling in the nervous system could be causing symptoms in GWI. Second, if found to be successful, then this will provide a low-cost, easy-to-implement treatment option for the many veterans suffering from this multi-symptom illness. Third, this research could lead to future studies to identify potential causes of this abnormal neurotransmission, to help prevent future illness onset.
Read the detailed description
Objective/ Hypothesis: The objective of this clinical trial is to test the effectiveness of a low-glutamate diet in GWI patients, as a way to mediate symptom occurrence by reducing excess glutamatergic neurotransmission.
Specific Aims:
Aim 1- Determine if GWI is a glutamate neurotoxicity disorder, by testing whether reduced exposure to dietary glutamate can modulate symptoms. Hypothesis: Dietary glutamate restriction will significantly reduce GWI symptoms, including fatigue, cognitive dysfunction, pain, problems sleeping, headache/migraine, and diarrhea; as measured by symptom questionnaire, dolorimetery, computerized cognitive testing, EEG and fMRI memory testing. Additionally, brain glutamate levels will be reduced after one month on the diet, as measured by magnetic resonance spectroscopy (MRS).
Aim 2- Confirm that altered dietary glutamate exposure was the cause of symptom improvement.
Hypothesis: Challenge with MSG, as compared to placebo, in a randomized, double-blind, placebo-controlled crossover challenge, will significantly increase the occurrence of symptoms, cause increased pain sensitivity as measured by dolorimetry, increased excitatory neurotransmission as measured by EEG, and a worsening of cognitive function as measured by computerized cognitive testing.
Study Design: 40 subjects will be recruited from around the US . After phone screening, eligible individuals will travel to Washington DC for their first visit, where subjects will undergo baseline testing, including assessment of symptoms, cognition, brain glutamate levels and working memory testing using fMRI. For phase 1, subjects will be randomized to a low-glutamate diet (n=20) or a waitlisted group (n=20 as controls), and symptom occurrence will be compared after one month. Waitlisted participants will follow the low-glutamate diet over the following month. At the end of phase 1, subjects will return to DC, will undergo post-diet assessment of symptoms (same as baseline), and then will move onto Phase 2 of the study, a randomized, double-blind, placebo-controlled crossover challenge, to test whether symptoms recur upon challenge with MSG and not with placebo. Subjects will be randomized as to which contingency (MSG or placebo) is received first, and will receive MSG for 3 consecutive days on one of the weeks and placebo for 3 consecutive days on the other week. Symptoms, EEG and cognition will be assessed on day 3 of challenges each week. All subjects will still be following the low-glutamate diet during the challenge period, so their only exposure to glutamate will be from the week they receive the MSG.
- Conditions
- Gulf War Syndrome
- Being tested
- Low-glutamate diet
- Keywords
- MSG, Gulf War Syndrome, Diet, Glutamate
- 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.
Low-glutamate dietOther
The dietary intervention consists of a one-month low-glutamate diet, followed by a randomized crossover challenge with MSG and placebo to measure return of symptoms.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 5 g of placebo (sugar and salt) will be administered in veggie capsules Receives: Other: Low-glutamate diet |
| MSG | Experimental | 5 grams of MSG will be administered in veggie capsules Receives: Other: Low-glutamate diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Symptom Score Change
The number and type of symptoms will be assessed with a symptom score measure
Measured: Baseline, 1 month, 5th week, 6th week
Secondary outcomes (1)
Cognitive Function
A computerized cognitive battery will measure cognitive function
Measured: Baseline, 1 month, 5th week, 6th week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start14 Nov 2017
- Primary completion7 Jul 2020
- Study completion31 Aug 2020
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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Subjects will be randomized to immediately start a one-month dietary intervention restricting consumption of glutamate, or will be waitlisted as a control group for the first month, and then will begin the one-month dietary intervention period (which will be completed at home). Then subjects will return to DC, will complete all measures again, and then will participate in a double-blind, placebo-controlled, crossover challenge with MSG and placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- American University
- Sponsor type
- University, hospital or other
- Collaborators
- Georgetown University, United States Department of Defense
- Responsible party
- Principal investigator, Kathleen Holton, American University
- Investigators
- Kathleen F Holton, PhD, Principal investigator, American University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03342482
- Sponsor's protocol ID
- IRB-2017-301
- Acronym
- GWI
- Status last verified
- Jan 2021
- First submitted
- 9 Nov 2017
- Last updated
- 12 Jan 2021
- 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 12 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutamate Neuro-Excitotoxicity in GWI
- ClinicalTrials.gov ID
- NCT03342482
- Acronym / sponsor ID
- GWI / IRB-2017-301
- Conditions
- Gulf War Syndrome
- Keywords
- MSG, Gulf War Syndrome, Diet, Glutamate
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- American UniversityUniversity, hospital or other
- Collaborators
- Georgetown University, United States Department of Defense
- Study start
- 14 Nov 2017 (actual)
- Primary completion
- 7 Jul 2020 (actual)
- Study completion
- 31 Aug 2020 (actual)
- First posted
- 17 Nov 2017 (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.
The objective of the proposed research is to examine whether dietary exposure to food additives containing glutamate may be contributing to symptoms in Gulf War Illness (GWI). The rationale for proposed study comes from data in the fibromyalgia field which suggests that reducing the consumption of dietary glutamate can reduce over-excitation in the nervous system, leading to symptom improvement. In prior research, a low-glutamate diet (restricting food additive consumption) was tested in fibromyalgia patients. After one-month on the diet, 84% of patients had >30% of their symptoms go away (with 11 symptoms remitting on average), and 8 subjects had complete remission of all symptoms. Subjects then had a significant return of symptoms upon challenge with monosodium glutamate (MSG) as compared to placebo. Since there is almost complete symptom overlap between fibromyalgia and GWI, it is of utmost importance to test this diet as a low-cost treatment option in GWI patients.
The findings from this research will ultimately be applicable to all GWI patients and potentially to other veterans with a similar symptom profile as well. The ultimate impact of this research could be quite profound, as it has the potential to impact all of the symptoms of GWI, as opposed to being a proposed treatment for only one of the symptoms. This dietary treatment has been shown to dramatically affect symptoms like fatigue, cognitive dysfunction, and pain; and thus, has the potential to dramatically improve quality of life for these individuals. Potential benefits of the treatment are great, and risks are minimal, as the treatment involves shifting the diet to a healthier, whole-food approach.
First, the study will confirm or negate the idea that abnormal glutamate signaling in the nervous system could be causing symptoms in GWI. Second, if found to be successful, then this will provide a low-cost, easy-to-implement treatment option for the many veterans suffering from this multi-symptom illness. Third, this research could lead to future studies to identify potential causes of this abnormal neurotransmission, to help prevent future illness onset.
Detailed description
Objective/ Hypothesis: The objective of this clinical trial is to test the effectiveness of a low-glutamate diet in GWI patients, as a way to mediate symptom occurrence by reducing excess glutamatergic neurotransmission.
Specific Aims:
Aim 1- Determine if GWI is a glutamate neurotoxicity disorder, by testing whether reduced exposure to dietary glutamate can modulate symptoms. Hypothesis: Dietary glutamate restriction will significantly reduce GWI symptoms, including fatigue, cognitive dysfunction, pain, problems sleeping, headache/migraine, and diarrhea; as measured by symptom questionnaire, dolorimetery, computerized cognitive testing, EEG and fMRI memory testing. Additionally, brain glutamate levels will be reduced after one month on the diet, as measured by magnetic resonance spectroscopy (MRS).
Aim 2- Confirm that altered dietary glutamate exposure was the cause of symptom improvement.
Hypothesis: Challenge with MSG, as compared to placebo, in a randomized, double-blind, placebo-controlled crossover challenge, will significantly increase the occurrence of symptoms, cause increased pain sensitivity as measured by dolorimetry, increased excitatory neurotransmission as measured by EEG, and a worsening of cognitive function as measured by computerized cognitive testing.
Study Design: 40 subjects will be recruited from around the US . After phone screening, eligible individuals will travel to Washington DC for their first visit, where subjects will undergo baseline testing, including assessment of symptoms, cognition, brain glutamate levels and working memory testing using fMRI. For phase 1, subjects will be randomized to a low-glutamate diet (n=20) or a waitlisted group (n=20 as controls), and symptom occurrence will be compared after one month. Waitlisted participants will follow the low-glutamate diet over the following month. At the end of phase 1, subjects will return to DC, will undergo post-diet assessment of symptoms (same as baseline), and then will move onto Phase 2 of the study, a randomized, double-blind, placebo-controlled crossover challenge, to test whether symptoms recur upon challenge with MSG and not with placebo. Subjects will be randomized as to which contingency (MSG or placebo) is received first, and will receive MSG for 3 consecutive days on one of the weeks and placebo for 3 consecutive days on the other week. Symptoms, EEG and cognition will be assessed on day 3 of challenges each week. All subjects will still be following the low-glutamate diet during the challenge period, so their only exposure to glutamate will be from the week they receive the MSG.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Subjects will be randomized to immediately start a one-month dietary intervention restricting consumption of glutamate, or will be waitlisted as a control group for the first month, and then will begin the one-month dietary intervention period (which will be completed at home). Then subjects will return to DC, will complete all measures again, and then will participate in a double-blind, placebo-controlled, crossover challenge with MSG and placebo.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Low-glutamate diet5 g of placebo (sugar and salt) will be administered in veggie capsules |
| MSG | Experimental | Other: Low-glutamate diet5 grams of MSG will be administered in veggie capsules |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males \& Females
- Served (and was deployed) in the Persian Gulf War
- Fulfill both Kansas and CDC definitions of GWI
- Stable medication regimen for 3 or more months
Key exclusion criteria (5 listed)
- Active Duty Military
- Current substance use disorder
- Unwilling to change diet for 2 months
- Severe asthma requiring past hospitalization
- Seizure disorder
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 |
|---|---|---|
| Low-glutamate dietThe dietary intervention consists of a one-month low-glutamate diet, followed by a randomized crossover challenge with MSG and placebo to measure return of symptoms. | Other | MSG, Placebo |
Primary outcome
Symptom Score Change
Time frame: Baseline, 1 month, 5th week, 6th week
The number and type of symptoms will be assessed with a symptom score measure
1 secondary outcome
Cognitive Function
Time frame: Baseline, 1 month, 5th week, 6th week
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 12 Jan 2021.
- Individual participant dataSharing planned: No
Related trials for Gulf War Syndrome
Not yet recruiting
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Clinical Evaluation of Montelukast in Veterans With Gulf War Illness
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Growth Hormone Replacement in Veterans With GWI and AGHD (GWIT)
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Resistant Potato Starch to Alleviate GWI
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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 principal investigator
American University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low-glutamate diet in people with Gulf War Syndrome, run by American University 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 5 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 12 Jan 2021. 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?
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?
Symptom Score Change (time frame: Baseline, 1 month, 5th week, 6th week). 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 12 Jan 2021.