Coenzyme Q10 Phase III Trial in Gulf War Illness

A Randomized, Double-blind Placebo-controlled Phase III Trial of Coenzyme Q10 in Gulf War Illness

The primary objective of this clinical trial is to determine if treatment with ubiquinol, a form of coenzyme Q10, improves the physical function of men and women Veterans suffering from Gulf War Illness (GWI). The primary outcome measure is a change from baseline on the Short Form Health Survey 36-item (SF-36), with respect to physical functioning and symptoms. Secondary outcome measures include changes from baseline levels on GWI-associated biomarkers in peripheral blood and GWI-associated symptoms of chronic pain, fatigue, insomnia, activity level, and cognitive and mental functioning.

Study Overview

• Status: Completed
• Conditions: Gulf War Illness; Chronic Fatigue; Coenzyme Q10; Ubiquinol
• Intervention / Treatment: Drug: Ubiquinol; Drug: Placebo

Detailed Description

As many as a third of the nearly 700,000 military personnel deployed during Desert Shield and Desert Storm (Aug 2, 1990 to July 31, 1991) in the Kuwaiti Theater of Operations are suffering from Gulf War Illness (GWI), an unexplained chronic illness characterized by multiple symptoms. Gulf War Veterans experienced environmental exposures that are known to be oxidative stressors which contribute to cell injury, resulting in mitochondrial dysfunction Exploratory studies using interventions that support cell functioning and prevent or repair stress mediators suggest a role for these targeted interventions, such as Coenzyme Q10. The goal of this clinical trial is to determine if Coenzyme Q10 is effective in increasing physical functioning for Veterans with Gulf War Illness.

This is a randomized, two group, double blind, placebo controlled, Phase III clinical trial. The treatment group will receive a (2x200 mg for 2 months and 1x200 mg for 4 months) once a day of ubiquinol for 6 months. The placebo group will receive matching placebo (2x200 mg for 2 months and 1x200 mg for 4 months) once a day of ubiquinol for 6 months. The primary outcome measure for this clinical trial is a change from baseline of SF-36, with respect to physical functioning and symptoms. The secondary outcome measures include changes from baseline of peripheral blood levels of biomarkers, and of GWI-associated symptoms of chronic pain, fatigue, sleep issues, and cognitive impairment.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33125
      • Miami VA Healthcare System, Miami, FL
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Health Care System, Minneapolis, MN
  • New York
    • Bronx, New York, United States, 10468
      • James J. Peters VA Medical Center, Bronx, NY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female Veterans who were deployed in 1990 -1991 Gulf War.
• Veterans who currently meet the Kansas Gulf War Study Case Definition for Gulf War Illness.
• Veterans who were in good health based on medical history prior to 1990.
• Veterans whose severity of illness is moderate to severe, evidenced by scoring less than 30 of 100 on the physical domain of SF36.

Exclusion Criteria:

• Veteran has a condition that may interfere with the ability to accurately report symptoms, such as:

  • severe psychiatric problems
  • schizophrenia
  • bipolar disorder
  • major depression with psychotic or melancholic features
  • delusional disorders alcohol or drug dependence requiring hospitalization, or regular illegal drug use or other psychiatric condition requiring inpatient stay in the 6 months prior to study entry.
  • Has dementias of any type
  • Currently does not have exclusionary conditions that could reasonably be responsible for the symptoms in multi-symptom disorders, as determined by Investigator (based on Reeves et al.2003).
  • Is pregnant or breastfeeding or plans to become pregnant within the next 6 months.

• Medical conditions excluded:

  • organ failure
  • defined rheumatologic inflammatory disorders
  • chronic active infections such as HIV, hepatitis B and C, or transplant
  • primary sleep disorders

• Medications that could potentially impact immune function excluded:

  • steroids
  • immune-suppressives
  • nutraceuticals that are formulated to impact mitochondrial function or oxidative stress
  • Biologic response modifiers within 3 months of study entry.
• Current use of Coumadin (given the vitamin K structural similarity of CoQ10)
• Known allergy to CoQ10 and/or inactive ingredients of active and placebo soft gelatin capsules
• Willingness to have 12 weeks of washout of current CoQ10, ubiquinol, or ubiquinone supplements will be required between the screening and baseline visits.
• Common multivitamin preparations will be allowed if taken without change throughout the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ubiquinol; Take oral tablets as directed (2x200 mg for 2 months; 1x200 mg for 4 months) with food each morning- upon waking	Drug: Ubiquinol; Take oral tablets as directed (2x200 mg for 2 months; 1x200 mg for 4 months) with food each morning- upon waking; Other Names: Coenzyme Q10, CoQ10
Placebo Comparator: Placebo; Take oral tablets as directed (2x200 mg for 2 months; 1x 200 mg for 4 months) with food each morning-upon waking	Drug: Placebo; Take oral tablets as directed (2x200 mg for 2 months; 1x200 mg for 4 months) with food each morning- upon waking; Other Names: Sugar pill, inactive substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Veterans Short Form 36-Item Health Survey Physical Component Summary	Veterans Health Survey contains 36 items to measure health functioning from the patient's point of view. The scale is 0-100. The higher value indicates better physical health.	Baseline, Weeks 4, 8, 12, 16, 20, and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multidimensional Fatigue Inventory (MFI)	MFI asks questions about general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. The Multidimensional Fatigue Inventory score is 0-100. The higher value indicates more fatigue.	Baseline, Weeks 4, 8, 12, 16, 20, and 24
Gulf War Illness Health Symptom Checklist	The Gulf War Illness Health Symptoms Checklist asks questions about symptoms related to Gulf War Illness. The linear scale is 0-42. The higher value indicates more symptoms.	Baseline, Weeks 4, 8, 12, 16, 20, 24, and 28
Brief Pain Inventory	The Brief Pain Inventory is a linear scale of pain. The scale is 0-10. The higher value indicates more pain.	Baseline, Weeks 4, 8, 12, 16, 20, and 24
Pittsburgh Sleep Quality Index	The PSQI measures quality and patterns of sleep and wake cycles and is completed by the participant. The Pittsburgh Sleep Quality Index scale is 0-21. The higher value indicates more sleep disturbance.	Baseline, Weeks 4, 8, 12, 16, 20, and 24
Hamilton Anxiety Scale (HAM-A)	This measure allows the participant to rate levels of anxiety. The Hamilton Anxiety Scale is 0-56. The higher value indicates more anxiety.	Baseline, Weeks 8, 16, and 24
Hamilton Depression Scale (HAM-D)	This measure allows the participant to rate level of depression. The Hamilton Depression Scale is a linear scale 0-62. The higher value indicates more depression.	Baseline, Weeks 8, 16, and 24
Veterans Short Form 36-Item Health Survey: Mental Component Score (MCS)	Veterans Health Survey contains 36 items to measure health functioning from the patient's point of view. The Veterans Short Form 36-item Health Survey Mental Component Score scale is 0-100. The higher value indicates more favorable mental health.	Baseline, Weeks 4, 8, 12, 16, 20, and 24
Connors Continuous Performance Test (CPT-3): Hit Reaction Time	CPT-3 asks questions about cognitive symptoms related to attention and reaction time. The Connors Continuous Performance Test Hit Reaction Time scale is 0-No limit. The higher score indicates poorer outcomes.	Baseline, Weeks 8, 16, and 24
Connors Continuous Performance Test (CPT-3):Omissions T-score	CPT-3 asks questions about cognitive symptoms related to attention and reaction time. The Connors Continuous Performance Test Omissions score is 0-100. 50 indicates the population mean with a standard deviation of 10. The higher T-score indicates poorer outcomes.	Baseline, Weeks 8, 16, and 24
Connors Continuous Performance Test (CPT-3):Commissions T-score	CPT-3 asks questions about cognitive symptoms related to attention and reaction time. The Connors Continuous Performance Test Commissions T-score scale is 0-100. 50 indicates the population mean with a standard deviation of 10. The higher score indicates poorer outcomes.	Baseline, Weeks 8, 16, and 24
Brief Visual Memory Test (BVMT): Delayed Recall	BVMT asks questions about cognitive symptoms related to visual memory. The Brief Visual Memory Test Delayed Recall scale is 0-12. The higher value indicates better performance.	Baseline, Weeks 8, 16, and 24
Brief Visual Memory Test (BVMT): Percent Retained	BVMT asks questions about cognitive symptoms related to visual memory. The Brief Visual Memory Test Percent Retained score is 0-100. The higher value indicates better performance.	Baseline, Weeks 8, 16, and 24
California Verbal Learning Test (CVLT-II): Correct Trials # 1-5	CVLT-II asks questions about cognitive symptoms related to recall and memory. The California Verbal Learning Test (CVLT-II) Correct Trials #1-5 score is 0-80. The higher score indicates better performance.	Baseline, Weeks 8, 16, and 24
California Verbal Learning Test (CVLT-II): Short Delay	CVLT-II asks questions about cognitive symptoms related to recall and memory. The California Verbal Learning Test (CVLT-II) Short Delay Test scale is 0-16. The higher score indicates better performance.	Baseline, Weeks 8, 16, and 24
California Verbal Learning Test (CVLT-II): Long Delay Test	CVLT-II asks questions about cognitive symptoms related to recall and memory. The California Verbal Learning Test (CVLT-II) Long Delay Test scale is 0-16. The higher score indicates better performance.	Baseline, Weeks 8, 16, and 24
Davidson Trauma Scale	Davidson Trauma Scale asks questions about stress, arousal, and avoidance. The scale is 0 - 136. The higher value indicates worse outcome.	Baseline, Weeks 8, 16, and 24
FitBit Sleep Measurement - Total Sleep	FitBit measures the duration of sleep daily via a bracelet-type instrument worn on the participant's wrist throughout the study. No normative data for FitBit Sleep was available.	Baseline to 8 weeks, 8 weeks to 16 weeks, 16 weeks to 24 weeks
FitBit Sleep Measurement - Types of Sleep	FitBit measures the time spent in each type of sleep (Light, Deep, Rapid Eye Movement (REM)) daily via a bracelet-type instrument worn on the participant's wrist throughout the study. No normative data for FitBit Sleep was available.	Baseline to 8 weeks, 8 weeks to 16 weeks, 16 weeks to 24 weeks
Response to Therapy of Gulf War Illness-associated Peripheral Blood Biomarkers - Complete Blood Count (CBC) White Blood Cell Counts and Platelets	Peripheral blood biomarker levels are quantified by complete blood count (CBC) analyses: white blood cell (WBC) counts and platelets. Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24
Response to Therapy of Gulf War Illness-associated Peripheral Blood Biomarkers - Complete Blood Count (CBC) Red Blood Cell (RBC) Counts	Peripheral blood biomarker levels are quantified by complete blood count (CBC) analyses: red blood cell counts. Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24
Response to Therapy of Gulf War Illness-associated Peripheral Blood Biomarkers - Complete Blood Count (CBC) White Blood Cell Percentages	Peripheral blood biomarker levels are quantified by complete blood count (CBC) analyses: percentages of white blood cells. Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24
Response to Therapy of Gulf War Illness-associated Peripheral Blood Biomarkers - Complete Blood Count (CBC) Hemoglobin	Peripheral blood biomarker levels are quantified by complete blood count (CBC) analyses: hemoglobin. Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24
Response to Therapy of Gulf War Illness-associated Peripheral Blood Biomarkers - Complete Blood Count (CBC) Hematocrit	Peripheral blood biomarker levels are quantified by complete blood count (CBC) analyses: percentages of hematocrit in blood. Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24
Response to Therapy on Hypothalamic-Pituitary-Thyroid (HPT) Axis: TSH	Thyroid status is assessed using a chemiluminescent method: thyroid stimulating hormone (TSH). Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24
Response to Therapy on Hypothalamic-Pituitary-Thyroid (HPT) Axis: FT3	Thyroid status is assessed using a chemiluminescent method: Free triiodothyronine (FT3). Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24
Response to Therapy on Hypothalamic-Pituitary-Thyroid (HPT) Axis: FT4	Thyroid status is assessed using a chemiluminescent method: Free thyroxine (FT4). Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24
Response to Therapy on Cortisol Levels	Cortisol will be measured using a 24-hour salivary collection to assess circadian rhythm.	Baseline, Weeks 8, 16, and 24 upon waking, mid-morning, evening, and sleep for each.
Response to Therapy on Hypothalamic-Pituitary-Gonadal (HPG) Axis: Testosterone	HPG will measure testosterone. Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24
Response to Therapy on Hypothalamic-Pituitary-Gonadal (HPG) Axis: Progesterone	HPG will measure progesterone. Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24
Response to Therapy on Hypothalamic-Pituitary-Gonadal (HPG) Axis: Estradiol	HPG will measure estradiol. Average values fell within the normal range for this type of assay.	Baseline, Weeks 8, 16, and 24

Collaborators and Investigators

• Sponsor: VA Office of Research and Development

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2017
• Primary Completion (Actual): October 7, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: July 28, 2016
• First Submitted That Met QC Criteria: August 9, 2016
• First Posted (Estimate): August 12, 2016

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 10, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Pathologic Processes; Chronic Pain; Nervous System Diseases; Dementia; Physiological Effects of Drugs; Mental Disorders; Pharmacologic Actions; Therapeutic Uses; Gulf war illness; Anti-Inflammatory Agents; Chronic fatigue; Cognitive Disorders; Neurologic manifestations; Ubiquinol/ubiquinone; Hormones, Hormone Substitutes, and Hormone Antagon
• Additional Relevant MeSH Terms: Fatigue; Physiological Effects of Drugs; Micronutrients; Vitamins; Coenzyme Q10
• Other Study ID Numbers: SPLD-04-15F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No