OEA for Targeting Lipid Metabolism in GWI

Gulf War Illness Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05252949
• Other study ID #: RI-OEA-001
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 10, 2021
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Roskamp Institute Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gulf War Illness

Intervention

Dietary Supplement:
• Oleoylethanolamide (OEA)
Oleoylethanolamide (OEA) is a naturally occurring ethanolamide that acts as a peroxisome proliferator-activated receptor alpha (PPAR-a) agonist, thereby modulating lipid profiles.
• Placebo
Visually matching placebo capsules will contain the same inactive ingredients present in the manufactured OEA capsules, with the exception of any OEA compound.

Locations

Country	Name	City	State
United States	The Roskamp Institute	Sarasota	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Roskamp Institute Inc.	United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (7)

Abdullah L, Crynen G, Reed J, Bishop A, Phillips J, Ferguson S, Mouzon B, Mullan M, Mathura V, Mullan M, Ait-Ghezala G, Crawford F. Proteomic CNS profile of delayed cognitive impairment in mice exposed to Gulf War agents. Neuromolecular Med. 2011 Dec;13(4):275-88. doi: 10.1007/s12017-011-8160-z. Epub 2011 Oct 11. — View Citation

Abdullah L, Evans JE, Bishop A, Reed JM, Crynen G, Phillips J, Pelot R, Mullan MA, Ferro A, Mullan CM, Mullan MJ, Ait-Ghezala G, Crawford FC. Lipidomic profiling of phosphocholine-containing brain lipids in mice with sensorimotor deficits and anxiety-like features after exposure to Gulf War agents. Neuromolecular Med. 2012 Dec;14(4):349-61. doi: 10.1007/s12017-012-8192-z. Epub 2012 Jul 14. — View Citation

Abdullah L, Evans JE, Joshi U, Crynen G, Reed J, Mouzon B, Baumann S, Montague H, Zakirova Z, Emmerich T, Bachmeier C, Klimas N, Sullivan K, Mullan M, Ait-Ghezala G, Crawford F. Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness. Toxicology. 2016 Nov 30;372:22-33. doi: 10.1016/j.tox.2016.10.012. Epub 2016 Oct 29. — View Citation

Abdullah L, Evans JE, Montague H, Reed JM, Moser A, Crynen G, Gonzalez A, Zakirova Z, Ross I, Mullan C, Mullan M, Ait-Ghezala G, Crawford F. Chronic elevation of phosphocholine containing lipids in mice exposed to Gulf War agents pyridostigmine bromide and permethrin. Neurotoxicol Teratol. 2013 Nov-Dec;40:74-84. doi: 10.1016/j.ntt.2013.10.002. Epub 2013 Oct 17. — View Citation

Emmerich T, Zakirova Z, Klimas N, Sullivan K, Shetty AK, Evans JE, Ait-Ghezala G, Laco GS, Hattiangady B, Shetty GA, Mullan M, Crynen G, Abdullah L, Crawford F. Phospholipid profiling of plasma from GW veterans and rodent models to identify potential biomarkers of Gulf War Illness. PLoS One. 2017 Apr 28;12(4):e0176634. doi: 10.1371/journal.pone.0176634. eCollection 2017. — View Citation

Joshi U, Evans JE, Joseph R, Emmerich T, Saltiel N, Lungmus C, Oberlin S, Langlois H, Ojo J, Mouzon B, Paris D, Mullan M, Jin C, Klimas N, Sullivan K, Crawford F, Abdullah L. Oleoylethanolamide treatment reduces neurobehavioral deficits and brain pathology in a mouse model of Gulf War Illness. Sci Rep. 2018 Aug 27;8(1):12921. doi: 10.1038/s41598-018-31242-7. Erratum In: Sci Rep. 2019 Jul 24;9(1):11011. — View Citation

White RF, Steele L, O'Callaghan JP, Sullivan K, Binns JH, Golomb BA, Bloom FE, Bunker JA, Crawford F, Graves JC, Hardie A, Klimas N, Knox M, Meggs WJ, Melling J, Philbert MA, Grashow R. Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment. Cortex. 2016 Jan;74:449-75. doi: 10.1016/j.cortex.2015.08.022. Epub 2015 Sep 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Changes in fatigue	The study will use the Multidimensional Fatigue Inventory (MFI-20) to assess fatigue.	10 weeks
Secondary	Changes in mood	The study will use the Profile of Mood States (POMS) to assess mood.	10 weeks
Secondary	Changes in pain	The study will use the McGill Pain Questionnaire (SF-MPQ) to assess pain.	10 weeks
Secondary	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
Secondary	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
Secondary	Changes in quality of life	The study will use the Quality of Life Scale (SF36).	10 weeks