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| ID | Type | Description | Link |
|---|---|---|---|
| CDMRP-GW130015 | Other Grant/Funding Number | Congressionally Directed Medical Research Programs |
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| Name | Class |
|---|---|
| Congressionally Directed Medical Research Programs | FED |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Boswellia Serrata | Experimental | 400-800mg in capsule form by mouth every day |
|
| Curcumin | Experimental | 1000-2000mg in capsule form by mouth every day |
|
| Epimedium | Experimental | 1000-2000mg in capsule form by mouth every day |
|
| Fisetin | Experimental | 200-800mg in capsule form by mouth every day |
|
| Luteolin | Experimental | 200-400mg in capsule form by mouth every day |
|
| Nettle | Experimental | 435-1305mg in capsule form by mouth every day |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Boswellia Serrata | Dietary Supplement |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Week 17 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Week 17 |
| Change From Baseline in Fatigue Severity |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jarred W Younger, PhD | University of Alabama at Birmingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33915962 | Derived | 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. | |
| 33802381 |
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Participants also took a placebo for each botanical. The order is as follows for each botanical: 30 +/- 3 days pf baseline symptom reports, followed by 30+/- days of placebo, followed by 30+/- days days of lower-dose botanical, followed by 30+/- days of higher-dose botanical.
All participants took as least one botanical. Some then went on to take a second or even third botanical, but not all participants did this. The order was randomized, so not all participants took the same sequence of botanicals.
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | Participants enrolled in this study were assigned to receive placebo and up to three botanical agents in a psuedo-randomized order. For each botanical condition, participants first received a placebo, followed by a lower dose of botanical and a higher dose of botanical, for up to three different botanicals. After completing the full protocol of three botanicals, participants were then offered the opportunity to re-enroll to receive up to three additional botanicals. Dietary Supplement: Boswellia Serrata 400-800mg in capsule form by mouth every day Dietary Supplement: Curcumin 1000-2000mg in capsule form by mouth every day Dietary Supplement: Epimedium 1000-2000mg in capsule form by mouth every day Dietary Supplement: Fisetin 200-800mg in capsule form by mouth every day Dietary Supplement: Luteolin 200-400mg in capsule form by mouth every day Dietary Supplement: Nettle 435-1305mg in capsule form by mouth every day Dietary Supplement: Pycnogenol 200-400mg in capsule form by mouth every day Dietary Supplement: Reishi 1600-3200mg in capsule form by mouth every day Dietary Supplement: Resveratrol 200-600mg in capsule form by mouth every day Dietary Supplement: Placebo in capsule form by mouth every day |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants enrolled in this study were assigned to receive placebo and up to three botanical agents in a psuedo-randomized order. For each botanical condition, participants first received a placebo, followed by a lower dose of botanical and a higher dose of botanical, for up to three different botanicals. After completing the full protocol of three botanicals, participants were then offered the opportunity to re-enroll to receive up to three additional botanicals.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | Participants enrolled in this study were assigned to receive placebo and up to three botanical agents in a psuedo-randomized order. For each botanical condition, participants first received a placebo, followed by a lower dose of botanical and a higher dose of botanical, for up to three different botanicals. After completing the full protocol of three botanicals, participants were then offered the opportunity to re-enroll to receive up to three additional botanicals |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Participants assigned to multiple arms | Posted | Mean | Standard Error | units on a scale | Week 17 |
|
10 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Boswellia Serrata | 400-800mg in capsule form by mouth every day Boswellia Serrata |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Liver Enzyme | Hepatobiliary disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jarred Younger | University of Alabama at Birmingham | 205-975-5821 | youngerlab@uab.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 11, 2022 | Aug 25, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D018923 | Persian Gulf Syndrome |
| ID | Term |
|---|---|
| D009784 | Occupational Diseases |
| D000067398 | War-Related Injuries |
| D014947 | Wounds and Injuries |
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| ID | Term |
|---|---|
| D065260 | Frankincense |
| D003474 | Curcumin |
| C012596 | turmeric extract |
| C017875 | fisetin |
| D047311 | Luteolin |
| C048862 | stinging nettle lectin |
| C024070 | pycnogenols |
| D000077185 | Resveratrol |
| ID | Term |
|---|---|
| D012116 | Resins, Plant |
| D001704 | Biopolymers |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
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| Pycnogenol | Experimental | 200-400mg in capsule form by mouth every day |
|
| Reishi Mushroom | Experimental | 1600-3200mg in capsule form by mouth every day |
|
| Resveratrol | Experimental | 200-600mg in capsule form by mouth every day |
|
| Placebo | Placebo Comparator | in capsule form by mouth every day |
|
| Curcumin |
| Dietary Supplement |
|
|
| Epimedium | Dietary Supplement |
|
|
| Fisetin | Dietary Supplement |
|
| Luteolin | Dietary Supplement |
|
| Nettle | Dietary Supplement |
|
|
| Pycnogenol | Dietary Supplement |
|
|
| Reishi Mushroom | Dietary Supplement |
|
| Resveratrol | Dietary Supplement |
|
|
| Placebo | Dietary Supplement |
|
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). |
| 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). | 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). | 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). | 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). | 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). | Week 17 |
| 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. |
| 33802272 | Derived | 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. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Epimedium | 1000-2000mg in capsule form by mouth every day Epimedium |
| OG003 | Fisetin | 200-800mg in capsule form by mouth every day Fisetin |
| OG004 | Luteolin | 200-400mg in capsule form by mouth every day Luteolin |
| OG005 | Nettle | 435-1305mg in capsule form by mouth every day Nettle |
| OG006 | Pycnogenol | 200-400mg in capsule form by mouth every day Pycnogenol |
| OG007 | Reishi Mushroom | 1600-3200mg in capsule form by mouth every day Reishi Mushroom |
| OG008 | Resveratrol | 200-600mg in capsule form by mouth every day Resveratrol |
| OG009 | Placebo | in capsule form by mouth every day Placebo |
|
|
| Secondary | 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). | Participants assigned to multiple arms | Posted | Mean | Standard Error | units on a scale | Week 17 |
|
|
|
| Secondary | 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). | Participants assigned to multiple arms | Posted | Mean | Standard Error | units on a scale | Week 17 |
|
|
|
| Secondary | 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). | Participants assigned to multiple arms | Posted | Mean | Standard Error | units on a scale | Week 17 |
|
|
|
| Secondary | 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). | Participants assigned to multiple arms | Posted | Mean | Standard Error | units on a scale | Week 17 |
|
|
|
| Secondary | 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). | Participants assigned to multiple arms | Posted | Mean | Standard Error | units on a scale | Week 17 |
|
|
|
| Secondary | 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). | Participants assigned to multiple arms | Posted | Mean | Standard Error | units on a scale | Week 17 |
|
|
|
| Secondary | 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). | Participants assigned to multiple arms | Posted | Mean | Standard Error | units on a scale | Week 17 |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Curcumin | 1000-2000mg in capsule form by mouth every day Curcumin | 0 | 10 | 0 | 10 | 0 | 10 |
| EG002 | Epimedium | 1000-2000mg in capsule form by mouth every day Epimedium | 0 | 11 | 0 | 11 | 0 | 11 |
| EG003 | Fisetin | 200-800mg in capsule form by mouth every day Fisetin | 0 | 11 | 0 | 11 | 0 | 11 |
| EG004 | Luteolin | 200-400mg in capsule form by mouth every day Luteolin | 0 | 11 | 0 | 11 | 0 | 11 |
| EG005 | Nettle | 435-1305mg in capsule form by mouth every day Nettle | 0 | 12 | 0 | 12 | 1 | 12 |
| EG006 | Pycnogenol | 200-400mg in capsule form by mouth every day Pycnogenol | 0 | 11 | 0 | 11 | 0 | 11 |
| EG007 | Reishi Mushroom | 1600-3200mg in capsule form by mouth every day Reishi Mushroom | 0 | 10 | 0 | 10 | 0 | 10 |
| EG008 | Resveratrol | 200-600mg in capsule form by mouth every day Resveratrol | 0 | 10 | 0 | 10 | 0 | 10 |
| EG009 | Placebo | in capsule form by mouth every day Placebo | 0 | 96 | 0 | 96 | 0 | 96 |
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| D053147 |
| Plant Exudates |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D036381 | Diarylheptanoids |
| D006536 | Heptanes |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D047309 | Flavones |
| D005419 | Flavonoids |
| D002867 | Chromones |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D000081225 | Stilbestrols |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D059808 | Polyphenols |