Effects of Botanical Microglia Modulators in Gulf War Illness

The University of Alabama at Birmingham

Status: Completed

Conditions: Gulf War Illness

Treatments: Dietary Supplement: Epimedium; Dietary Supplement: Luteolin; Dietary Supplement: Pycnogenol; Dietary Supplement: Nettle; Dietary Supplement: Fisetin; Dietary Supplement: Boswellia Serrata; Dietary Supplement: Resveratrol; Dietary Supplement: Curcumin; Dietary Supplement: Placebo; Dietary Supplement: Reishi Mushroom

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT02909686

F150318011

CDMRP-GW130015 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 patients

Sex: Male

Ages: 39 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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36 participants in 10 patient groups, including a placebo group

Boswellia Serrata

Experimental group

Description:

400-800mg in capsule form by mouth every day

Treatment:

Dietary Supplement: Boswellia Serrata

Curcumin

Experimental group

Description:

1000-2000mg in capsule form by mouth every day

Treatment:

Dietary Supplement: Curcumin

Epimedium

Experimental group

Description:

1000-2000mg in capsule form by mouth every day

Treatment:

Dietary Supplement: Epimedium

Fisetin

Experimental group

Description:

200-800mg in capsule form by mouth every day

Treatment:

Dietary Supplement: Fisetin

Luteolin

Experimental group

Description:

200-400mg in capsule form by mouth every day

Treatment:

Dietary Supplement: Luteolin

Nettle

Experimental group

Description:

435-1305mg in capsule form by mouth every day

Treatment:

Dietary Supplement: Nettle

Pycnogenol

Experimental group

Description:

200-400mg in capsule form by mouth every day

Treatment:

Dietary Supplement: Pycnogenol

Reishi Mushroom

Experimental group

Description:

1600-3200mg in capsule form by mouth every day

Treatment:

Dietary Supplement: Reishi Mushroom

Resveratrol

Experimental group

Description:

200-600mg in capsule form by mouth every day

Treatment:

Dietary Supplement: Resveratrol

Placebo

Placebo Comparator group

Description:

in capsule form by mouth every day

Treatment:

Dietary Supplement: Placebo