Coenzyme Q10 Phase III Trial in Gulf War Illness

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Gulf War Illness, Chronic Fatigue, Ubiquinol, Coenzyme Q10

Intervention / Treatment
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* Drug: Ubiquinol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Pain, Cognitive Disorders, Inflammation, Neurologic manifestations, Dementia, Mental Disorders, Ubiquinol/ubiquinone, Pathologic Processes, Nervous System Diseases, Hormones, Hormone Substitutes, and Hormone Antagon, Anti-Inflammatory Agents, Pharmacologic Actions, Therapeutic Uses, Physiological Effects of Drugs, Gulf war illness, Chronic fatigue