Clinical trial NCT02909686: Effects of Botanical Microglia Modulators in Gulf War Illness
Official title: Effects of Botanical Microglia Modulators in Gulf War Illness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gulf War Illness
Keywords: Gulf War Syndrome
Chronic Multisymptom Illnesses
Medically Unexplained Illnesses
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Congressionally Directed Medical Research Programs
First posted: 2016-09-21
Enrollment: 36
Sex: MALE
Minimum age (years): 39
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief 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. If one of those supplements helps the symptoms of GWI, it will give the investigators information about what is wrong in people with GWI.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Positive rheumatoid factor at screening
2. Positive anti-nuclear antibody at screening
3. C-reactive protein\> 3mg/L at screening
4. Erythrocyte Sedimentation Rate\> 40mm/hr at screening
5. Auto-immune disorder
6. Diagnosed Rheumatologic Condition
7. Major PTSD symptoms
8. Hypotension (under 90/60 mm Hg) or history of cardiovascular disease
9. Antihypertensive, anticoagulant medication, nitroglycerine, lithium medication use
10. Diabetes with Hemoglobin A1C \>9%
11. History of anaphylaxis to study botanical compounds
12. Current daily use of opioid medication
13. Hospital Anxiety and Depression Scale, Depression subscale score of 16 or higher at baseline
14. Current litigation of worker's compensation claim
15. Blood or clotting disorder
16. Acute infection (body temperature over 100 degrees F)
17. Current daily use of confounding-anti-inflammatory medication as part of regular medication regimen
18. Individuals that are not able to read \& understand English

Primary outcomes:
measure: Change From Baseline in Overall Gulf War Illness Disease Severity
timeFrame: Week 17
Secondary outcomes:
measure: Change From Baseline in Pain Severity
timeFrame: Week 17
measure: Change From Baseline in Fatigue Severity
timeFrame: Week 17
measure: Change From Baseline in Cognitive Symptom Severity
timeFrame: Week 17
measure: Change From Baseline in Mood Symptom Severity
timeFrame: Week 17
measure: Change From Baseline in Dermatological Symptom Severity
timeFrame: Week 17
measure: Change From Baseline in Respiratory Symptom Severity
timeFrame: Week 17
measure: Change From Baseline in Gastrointestinal Symptom Severity
timeFrame: Week 17
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Jarred W Younger, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.