OEA for Targeting Lipid Metabolism in GWI

Study Overview
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Brief Summary
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The study is a single site, randomized, double-blind, placebo-controlled study with an open label extension to evaluate the effects of Oleoylethanolamine (OEA) on blood lipid and immune biomarkers in participants with Gulf War Illness (GWI).

Detailed Description
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The 1991 Gulf War (GW) was fought by a coalition of 30 countries that included 700,000 U.S. troops. Although the war itself lasted two months, adverse health consequences from this conflict are still experienced by GW veterans. Soon after their return, many soldiers started reporting multiple, seemingly unrelated symptoms, such as memory impairment, fatigue, gastrointestinal problems, and widespread pain. This illness is termed Gulf War Illness (GWI) and affects about 32% of GW veterans. Several animal studies suggest that GWI presentation involves disturbed immune responses in the brain that correspond with altered lipid metabolism. Many of these lipid alterations are detected in blood of veterans with GWI and point to an abnormal function of peroxisomes and mitochondria which regulate lipids that are required for cellular signaling and for maintaining normal physiology. The investigators' preclinical studies using a GWI mouse model showed that targeting peroxisomal lipid metabolism with oleoylethanolamide (OEA) reduced corrected immune function and normalized brain and blood lipid profiles in GWI mice. Therefore, the objective of this pilot clinical research study is to determine if OEA supplementation in veterans with GWI maintains healthy blood lipid and immune profiles.

Official Title
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A Randomized, Double-blind, Placebo-controlled Clinical Trial of Oleoylethanolamide (OEA) for Targeting Lipid Metabolism in Gulf War Illness

Conditions
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Gulf War Illness

Intervention / Treatment
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* Dietary Supplement: Oleoylethanolamide (OEA)
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both genders, all ethnic groups, and ages up to 70. Subject willing and able to give informed consent. Medically stable as per the investigator's discretion. Negative urine pregnancy test for females of childbearing potential. A woman is considered of childbearing potential unless she is surgically sterile (hysterectomy or tubal ligation) or is postmenopausal (no menstrual cycle for 2 years or more). Must be willing to use adequate birth control during the study and for 30 days after the last dose. Females agreeing to take an acceptable form of birth control per investigator discretion (where relevant). Females must prevent pregnancy or otherwise be unable to conceive. Veterans deployed to the Gulf War between August 1990 and August 1991. Veteran meets criteria for the CDC Chronic Multisymptom Illness (CMI) GWI definition or Kansas GWI definition. Weight of 50.0kg - 200.0kg (110lbs - 440lbs). Exclusion Criteria: Diagnosed by a physician with medical or psychiatric conditions that would account for their symptoms or interfere with their ability to report their symptoms. Female subject is either pregnant or nursing. Have contraindications, allergy, or sensitivity to OEA, olive oil, or excipients (microcrystalline cellulose, silicon dioxide, magnesium stearate, macrogol polyvinyl alcohol copolymer, talc, titanium dioxide, glycerol monocaprylocaprate and polyvinyl alcohol). Any significant medical condition that could interfere with study conduct, as per investigator discretion. These may include but are not limited to the following: untreated chronic hypertension (defined as systolic > 180 mmHg; diastolic >110 mmHg), myocardial infarction within 6 months of screening, renal failure, hepatic failure, and/or receiving chemotherapy. Clinically significant lab values for clinical laboratory assessments. Poor venous access. Current use of any OEA supplement products within 30 days of screening. Participation in another clinical trial involving dietary or pharmaceutical intervention within 90 days of screening.

Ages Eligible for Study
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Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We will administer either OEA or placebo to the study participants over a blinded period of 10 weeks, followed by an open label phase with all participants receiving OEA for 5 weeks.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study Supplement: OEA<br>26 subjects will take the supplement (oleoylethanolamide) during the first phase of the study. 200mg will be taken twice a day for the 10-week period in phase one. | Dietary Supplement: Oleoylethanolamide (OEA)<br>* Oleoylethanolamide (OEA) is a naturally occurring ethanolamide that acts as a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, thereby modulating lipid profiles.<br>|
| Placebo Comparator: Control<br>26 subjects will take the placebo during the first phase of the study (10 weeks). | Dietary Supplement: Placebo<br>* Visually matching placebo capsules will contain the same inactive ingredients present in the manufactured OEA capsules, with the exception of any OEA compound.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in lipid biomarker profiles | The primary objective of the study is to assess the change in lipid levels in the blood between the two treatment arms over the 10-week placebo-controlled phase. | 10 weeks | 
| Changes in immune biomarker profiles | The primary objective of the study is to assess the change in cytokine levels in the blood between the two treatment arms over the 10-week placebo-controlled phase. | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in fatigue | The study will use the Multidimensional Fatigue Inventory (MFI-20) to assess fatigue. | 10 weeks | 
| Changes in mood | The study will use the Profile of Mood States (POMS) to assess mood. | 10 weeks | 
| Changes in pain | The study will use the McGill Pain Questionnaire (SF-MPQ) to assess pain. | 10 weeks | 
| Changes in cognition (neurocognitive) | The study will use the CNS Vital Signs computerized neurocognitive assessment software to assess memory. The computerized test uses individual tests to comprise a neurocognitive index score that can be used to evaluate neurocognitive status. | 10 weeks | 
| Changes in cognition (neuropsychological) | The study will use the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) cognitive test to assess memory. The test incorporates immediate memory, visuospatial/constructional, language, attention, and delayed memory components to determine a total scaled score for neuropsychological status. This total score ranges from 200 to 800, with higher scores increasing the associated percentile. | 10 weeks | 
| Changes in quality of life | The study will use the Quality of Life Scale (SF36). | 10 weeks |