Coenzyme Q10 Phase III Trial in Gulf War Illness

VA Office of Research and Development100 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Eligibility

Sex: ALLMin age: 35 YearsMax age: 70 Years

Medical Language ↔ Plain English

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.

Locations (4)

Miami VA Healthcare System, Miami, FL

Miami, Florida, United States

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, United States

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, United States

Outcomes

Primary Outcomes

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.

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Weeks 8, 16, and 24

Coenzyme Q10 Phase III Trial in Gulf War Illness

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes