Gulf War IllnessNCT02909686

Effects of Botanical Microglia Modulators in Gulf War Illness

A study testing Boswellia Serrata, Curcumin and Epimedium in people with Gulf War Illness, run by University of Alabama at Birmingham at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The overall objective of this protocol is to test if Gulf War Illness (GWI) involves chronic inflammation that cannot be measured with typical techniques. The investigators will be observing the effects of nine different botanical compounds (supplements) that are known to suppress inflammation. Read more about this study

Who is it for?: Ages 39 to 65 years, men only
Conditions the study is for: Gulf War Illness
What is being tested?: Boswellia Serrata, Curcumin and Epimedium
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 36 participants
Where: 1 siteUnited States
Study dates: Jul 2016to Sep 2022
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 39 to 65 years
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

Male
Age 39-65, inclusive
Veterans who meet the Kansas inclusion criteria for GWI
Present in Persian Gulf between 1990 and August 1991
Patient completes daily report during 2 week baseline period (at least 80% completion rate)
Able to receive a venous blood draw

Who cannot join

Positive rheumatoid factor at screening
Positive anti-nuclear antibody at screening
C-reactive protein> 3mg/L at screening
Erythrocyte Sedimentation Rate> 40mm/hr at screening
Auto-immune disorder
Diagnosed Rheumatologic Condition

Show all 18Show fewer

Major PTSD symptoms
Hypotension (under 90/60 mm Hg) or history of cardiovascular disease
Antihypertensive, anticoagulant medication, nitroglycerine, lithium medication use
Diabetes with Hemoglobin A1C >9%
History of anaphylaxis to study botanical compounds
Current daily use of opioid medication
Hospital Anxiety and Depression Scale, Depression subscale score of 16 or higher at baseline
Current litigation of worker's compensation claim
Blood or clotting disorder
Acute infection (body temperature over 100 degrees F)
Current daily use of confounding-anti-inflammatory medication as part of regular medication regimen
Individuals that are not able to read \& understand English

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Alabama at Birmingham
Birmingham, Alabama, 35294

Other trials in United States

About this study

Read the detailed description

There is still a poor understanding of the pain, fatigue, and other symptoms that affect approximately 250,000 veterans. The precise mechanism of Gulf War Illness (GWI) is not understood, and there is no targeted treatment for the condition. A current model for GWI points to the central nervous system, immune cells, called microglia that may be hyperactive in patients with GWI. Discovering effective treatments for this disorder is a top priority of GWI research.

Given the investigator's preliminary data, it is suspected that GWI is a form of low-level neuroinflammation that involves hypersensitivity of receptors on microglia. In order to help test that hypothesis, the investigators will be administering supplements that have been shown in vitro or animal in vivo to suppress microglia function in a way that is anti-inflammatory and neuroprotective. If any of these agents suppress symptoms in GWI, it will give the investigators important information about the disease that may allow for creation of better diagnostic tools and treatments in future research studies. Observing the effects of the selected nine anti-inflammatory botanical compounds, in this clinical study, is a strong compliment to the ongoing mechanistic GWI research.

Conditions: Gulf War Illness
Being tested: Boswellia Serrata, Curcumin, Epimedium, Fisetin, Luteolin
Keywords: Gulf War Syndrome, Chronic Multisymptom Illnesses, Medically Unexplained Illnesses
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.

Boswellia SerrataDietary supplement
Also called Indian frankincense
CurcuminDietary supplement
Also called Curcumasorb, Turmeric extract, Meriva
EpimediumDietary supplement
Also called Barrenwort, Bishop's Hat, Fairy Wings, Horny Goat Weed
FisetinDietary supplement
LuteolinDietary supplement
NettleDietary supplement
Also called Common Nettle, urtica dioica, Stinging Nettle
PycnogenolDietary supplement
Also called Maritime Pine Extract, Pine Bark Extract
Reishi MushroomDietary supplement
ResveratrolDietary supplement
Also called Red Wine Extract
PlaceboDietary supplement

Study groups in NCT02909686
Study group	Role	What they receive
Boswellia Serrata	Experimental	400-800mg in capsule form by mouth every day Receives: Dietary Supplement: Boswellia Serrata
Curcumin	Experimental	1000-2000mg in capsule form by mouth every day Receives: Dietary Supplement: Curcumin
Epimedium	Experimental	1000-2000mg in capsule form by mouth every day Receives: Dietary Supplement: Epimedium
Fisetin	Experimental	200-800mg in capsule form by mouth every day Receives: Dietary Supplement: Fisetin
Luteolin	Experimental	200-400mg in capsule form by mouth every day Receives: Dietary Supplement: Luteolin
Nettle	Experimental	435-1305mg in capsule form by mouth every day Receives: Dietary Supplement: Nettle
Pycnogenol	Experimental	200-400mg in capsule form by mouth every day Receives: Dietary Supplement: Pycnogenol
Reishi Mushroom	Experimental	1600-3200mg in capsule form by mouth every day Receives: Dietary Supplement: Reishi Mushroom
Resveratrol	Experimental	200-600mg in capsule form by mouth every day Receives: Dietary Supplement: Resveratrol
Placebo	Placebo comparator	in capsule form by mouth every day Receives: Dietary Supplement: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Overall Gulf War Illness Disease Severity
Self reported Gulf War Illness symptom severity evening reports were collected for the duration of the study. Scale= change from baseline in overall GWI Disease severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Measured: Week 17

Secondary outcomes (7)

Change From Baseline in Pain Severity
Self reported pain symptom severity evening reports were collected for the duration of the study. Scale= change from baseline in overall GWI pain severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Measured: Week 17
Change From Baseline in Fatigue Severity
Self reported fatigue symptom severity evening reports were collected for the duration of the study. Scale= change from baseline in overall GWI fatigue severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Measured: Week 17
Change From Baseline in Cognitive Symptom Severity
Self reported Cognitive Symptom Severity evening reports were collected for the duration of the study. Scale= change from baseline in overall Cognitive Symptom Severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Measured: Week 17
Change From Baseline in Mood Symptom Severity
Self reported Mood Symptom Severity evening reports were collected for the duration of the study. Scale= change from baseline in overall Mood Symptom Severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Measured: Week 17
Change From Baseline in Dermatological Symptom Severity
Self reported Dermatological Symptom Severity evening reports were collected for the duration of the study. Scale= change from baseline in overall Dermatological Symptom Severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Measured: Week 17
Change From Baseline in Respiratory Symptom Severity
Self reported Respiratory Symptom Severity evening reports were collected for the duration of the study. Scale= change from baseline in overall Respiratory Symptom Severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Measured: Week 17
Change From Baseline in Gastrointestinal Symptom Severity
Self reported Gastrointestinal Symptom Severity evening reports were collected for the duration of the study. Scale= change from baseline in overall Gastrointestinal Symptom Severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Measured: Week 17

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2016Sep 2022

First posted21 Sep 2016 (estimated)
Study startJul 2016
Primary completionSep 2019
Study completionSep 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Gulf War IllnessStudies of the same condition, open and under way.
More trials run by University of Alabama at BirminghamThe 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: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02909686
Sponsor's protocol ID: F150318011
Other IDs: CDMRP-GW130015
Status last verified: Dec 2024
First submitted: 13 Sep 2016
Last updated: 24 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Younger J, Donovan EK, Hodgin KS, Ness TJ. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Reishi Mushroom (Ganoderma lucidum), Stinging Nettle (Urtica dioica), and Epimedium (Epimedium sagittatum). Int J Environ Res Public Health. 2021 Apr 1;18(7):3671. doi: 10.3390/ijerph18073671.
PubMed 33915962
Hodgin KS, Donovan EK, Kekes-Szabo S, Lin JC, Feick J, Massey RL, Ness TJ, Younger JW. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea). Int J Environ Res Public Health. 2021 Mar 3;18(5):2483. doi: 10.3390/ijerph18052483.
PubMed 33802381
Donovan EK, Kekes-Szabo S, Lin JC, Massey RL, Cobb JD, Hodgin KS, Ness TJ, Hangee-Bauer C, Younger JW. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Curcumin (Curcuma longa), Boswellia (Boswellia serrata), and French Maritime Pine Bark (Pinus pinaster). Int J Environ Res Public Health. 2021 Mar 3;18(5):2468. doi: 10.3390/ijerph18052468.
PubMed 33802272

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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
Recruiting
Mechanisms of Gulf War Illness
Gulf War Illness, Irritable Bowel Syndrome
RecruitingPhase 2
Resistant Potato Starch to Alleviate GWI
Gulf War Illness
Recruiting
Machine Learning in Guiding rTMS Treatment for GWI-Related Headaches and Body Pain
Gulf War Illness, Headache

All Gulf War Illness trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Botanical Microglia Modulators in Gulf War Illness
ClinicalTrials.gov ID: NCT02909686
Acronym / sponsor ID: F150318011
Conditions: Gulf War Illness
Keywords: Gulf War Syndrome, Chronic Multisymptom Illnesses, Medically Unexplained Illnesses
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: University of Alabama at BirminghamUniversity, hospital or other
Collaborators: Congressionally Directed Medical Research Programs
Study start: Jul 2016 (actual)
Primary completion: Sep 2019 (actual)
Study completion: Sep 2022 (actual)
First posted: 21 Sep 2016 (estimated)
Results: Posted 24 Jan 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 10

Arm	Type	Receives
Boswellia Serrata	Experimental	Dietary Supplement: Boswellia Serrata400-800mg in capsule form by mouth every day
Curcumin	Experimental	Dietary Supplement: Curcumin1000-2000mg in capsule form by mouth every day
Epimedium	Experimental	Dietary Supplement: Epimedium1000-2000mg in capsule form by mouth every day
Fisetin	Experimental	Dietary Supplement: Fisetin200-800mg in capsule form by mouth every day
Luteolin	Experimental	Dietary Supplement: Luteolin200-400mg in capsule form by mouth every day
Nettle	Experimental	Dietary Supplement: Nettle435-1305mg in capsule form by mouth every day
Pycnogenol	Experimental	Dietary Supplement: Pycnogenol200-400mg in capsule form by mouth every day
Reishi Mushroom	Experimental	Dietary Supplement: Reishi Mushroom1600-3200mg in capsule form by mouth every day
Resveratrol	Experimental	Dietary Supplement: Resveratrol200-600mg in capsule form by mouth every day
Placebo	Placebo comparator	Dietary Supplement: Placeboin capsule form by mouth every day

Who may qualify

Ages: 39 to 65 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Male
Age 39-65, inclusive
Veterans who meet the Kansas inclusion criteria for GWI
Present in Persian Gulf between 1990 and August 1991
Patient completes daily report during 2 week baseline period (at least 80% completion rate)

Key exclusion criteria (18 listed)

Positive rheumatoid factor at screening
Positive anti-nuclear antibody at screening
C-reactive protein> 3mg/L at screening
Erythrocyte Sedimentation Rate> 40mm/hr at screening
Auto-immune 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
Boswellia SerrataAlso: Indian frankincense	Dietary supplement	Boswellia Serrata
CurcuminAlso: Curcumasorb, Turmeric extract, Meriva	Dietary supplement	Curcumin
EpimediumAlso: Barrenwort, Bishop's Hat, Fairy Wings, Horny Goat Weed	Dietary supplement	Epimedium
Fisetin	Dietary supplement	Fisetin
Luteolin	Dietary supplement	Luteolin
NettleAlso: Common Nettle, urtica dioica, Stinging Nettle	Dietary supplement	Nettle
PycnogenolAlso: Maritime Pine Extract, Pine Bark Extract	Dietary supplement	Pycnogenol
Reishi Mushroom	Dietary supplement	Reishi Mushroom
ResveratrolAlso: Red Wine Extract	Dietary supplement	Resveratrol
Placebo	Dietary supplement	Placebo

Primary outcome

Change From Baseline in Overall Gulf War Illness Disease Severity
Time frame: Week 17
Self reported Gulf War Illness symptom severity evening reports were collected for the duration of the study. Scale= change from baseline in overall GWI Disease severity (-100 to +100, with positive numbers indicating how much the symptom improved).

7 secondary outcomes

Change From Baseline in Pain Severity
Time frame: Week 17
Change From Baseline in Fatigue Severity
Time frame: Week 17
Change From Baseline in Cognitive Symptom Severity
Time frame: Week 17
Change From Baseline in Mood Symptom Severity
Time frame: Week 17
Change From Baseline in Dermatological Symptom Severity
Time frame: Week 17
Change From Baseline in Respiratory Symptom Severity
Time frame: Week 17
Change From Baseline in Gastrointestinal Symptom Severity
Time frame: Week 17

Results and safety

Results posted to the registry on 24 Jan 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Participants	96	91

Primary outcome: Change From Baseline in Overall Gulf War Illness Disease Severity

Time frame: Week 17. Mean (Standard Error). Unit: units on a scale

Measure	Boswellia Serrata n = 10	Curcumin n = 10	Epimedium n = 10	Fisetin n = 10	Luteolin n = 10	Nettle n = 10	Pycnogenol n = 10	Reishi Mushroom n = 10	Resveratrol n = 9	Placebo n = 89
Value	13 (.43)	0 (.32)	8 (1.56)	-1 (2.08)	12 (.90)	19 (1.08)	15 (1.18)	-5 (2.08)	14 (1.1)	7 (1.37)

Population analysed: Participants assigned to multiple arms

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: 10 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Boswellia Serrata	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Curcumin	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Epimedium	0 of 11 (0%)	0 of 11 (0%)	0 of 11
Fisetin	0 of 11 (0%)	0 of 11 (0%)	0 of 11
Luteolin	0 of 11 (0%)	0 of 11 (0%)	0 of 11
Nettle	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
Pycnogenol	0 of 11 (0%)	0 of 11 (0%)	0 of 11
Reishi Mushroom	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Resveratrol	0 of 10 (0%)	0 of 10 (0%)	0 of 10
Placebo	0 of 96 (0%)	0 of 96 (0%)	0 of 96

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33915962Younger J, Donovan EK, Hodgin KS, Ness TJ. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Reishi Mushroom (Ganoderma lucidum), Stinging Nettle (Urtica dioica), and Epimedium (Epimedium sagittatum). Int J Environ Res Public Health. 2021 Apr 1;18(7):3671. doi: 10.3390/ijerph18073671.
Derived from this study: PubMed 33802381Hodgin KS, Donovan EK, Kekes-Szabo S, Lin JC, Feick J, Massey RL, Ness TJ, Younger JW. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea). Int J Environ Res Public Health. 2021 Mar 3;18(5):2483. doi: 10.3390/ijerph18052483.
Derived from this study: PubMed 33802272Donovan EK, Kekes-Szabo S, Lin JC, Massey RL, Cobb JD, Hodgin KS, Ness TJ, Hangee-Bauer C, Younger JW. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Curcumin (Curcuma longa), Boswellia (Boswellia serrata), and French Maritime Pine Bark (Pinus pinaster). Int J Environ Res Public Health. 2021 Mar 3;18(5):2468. doi: 10.3390/ijerph18052468.

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
Recruiting
Mechanisms of Gulf War Illness
Gulf War Illness, Irritable Bowel Syndrome
RecruitingPhase 2
Resistant Potato Starch to Alleviate GWI
Gulf War Illness
Recruiting
Machine Learning in Guiding rTMS Treatment for GWI-Related Headaches and Body Pain
Gulf War Illness, Headache

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.

Jarred W Younger, PhD principal investigator

University of Alabama at Birmingham

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Boswellia Serrata, Curcumin and Epimedium in people with Gulf War Illness, run by University of Alabama at Birmingham 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 6 inclusion and 18 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 24 Jan 2025. 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?

Yes. Results are posted in the registry (first posted 24 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change From Baseline in Overall Gulf War Illness Disease Severity (time frame: Week 17). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02909686, which also lists 3 linked publications.

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 24 Jan 2025; AzTrials last refreshed its copy on 6 Nov 2026.