Clinical trial NCT02865460: Coenzyme Q10 Phase III Trial in Gulf War Illness
Official title: A Randomized, Double-blind Placebo-controlled Phase III Trial of Coenzyme Q10 in Gulf War Illness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gulf War Illness
Chronic Fatigue
Ubiquinol
Coenzyme Q10
Keywords: 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
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2016-08-12
Enrollment: 100
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Veterans Short Form 36-Item Health Survey Physical Component Summary
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Secondary outcomes:
measure: Multidimensional Fatigue Inventory (MFI)
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Gulf War Illness Health Symptom Checklist
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, 24, and 28
measure: Brief Pain Inventory
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Pittsburgh Sleep Quality Index
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Hamilton Anxiety Scale (HAM-A)
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Hamilton Depression Scale (HAM-D)
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Veterans Short Form 36-Item Health Survey: Mental Component Score (MCS)
timeFrame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
measure: Connors Continuous Performance Test (CPT-3): Hit Reaction Time
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Connors Continuous Performance Test (CPT-3):Omissions T-score
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Connors Continuous Performance Test (CPT-3):Commissions T-score
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Brief Visual Memory Test (BVMT): Delayed Recall
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Brief Visual Memory Test (BVMT): Percent Retained
timeFrame: Baseline, Weeks 8, 16, and 24
measure: California Verbal Learning Test (CVLT-II): Correct Trials # 1-5
timeFrame: Baseline, Weeks 8, 16, and 24
measure: California Verbal Learning Test (CVLT-II): Short Delay
timeFrame: Baseline, Weeks 8, 16, and 24
measure: California Verbal Learning Test (CVLT-II): Long Delay Test
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Davidson Trauma Scale
timeFrame: Baseline, Weeks 8, 16, and 24
measure: FitBit Sleep Measurement - Total Sleep
timeFrame: Baseline to 8 weeks, 8 weeks to 16 weeks, 16 weeks to 24 weeks
measure: FitBit Sleep Measurement - Types of Sleep
timeFrame: Baseline to 8 weeks, 8 weeks to 16 weeks, 16 weeks to 24 weeks
measure: Response to Therapy of Gulf War Illness-associated Peripheral Blood Biomarkers - Complete Blood Count (CBC) White Blood Cell Counts and Platelets
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Response to Therapy of Gulf War Illness-associated Peripheral Blood Biomarkers - Complete Blood Count (CBC) Red Blood Cell (RBC) Counts
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Response to Therapy of Gulf War Illness-associated Peripheral Blood Biomarkers - Complete Blood Count (CBC) White Blood Cell Percentages
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Response to Therapy of Gulf War Illness-associated Peripheral Blood Biomarkers - Complete Blood Count (CBC) Hemoglobin
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Response to Therapy of Gulf War Illness-associated Peripheral Blood Biomarkers - Complete Blood Count (CBC) Hematocrit
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Response to Therapy on Hypothalamic-Pituitary-Thyroid (HPT) Axis: TSH
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Response to Therapy on Hypothalamic-Pituitary-Thyroid (HPT) Axis: FT3
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Response to Therapy on Hypothalamic-Pituitary-Thyroid (HPT) Axis: FT4
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Response to Therapy on Cortisol Levels
timeFrame: Baseline, Weeks 8, 16, and 24 upon waking, mid-morning, evening, and sleep for each.
measure: Response to Therapy on Hypothalamic-Pituitary-Gonadal (HPG) Axis: Testosterone
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Response to Therapy on Hypothalamic-Pituitary-Gonadal (HPG) Axis: Progesterone
timeFrame: Baseline, Weeks 8, 16, and 24
measure: Response to Therapy on Hypothalamic-Pituitary-Gonadal (HPG) Axis: Estradiol
timeFrame: Baseline, Weeks 8, 16, and 24
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami VA Healthcare System, Miami, FL
state: Florida
city: Boston
country: United States
facility: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
state: Massachusetts
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System, Minneapolis, MN
state: Minnesota
city: Bronx
country: United States
facility: James J. Peters VA Medical Center, Bronx, NY
state: New York
Study officials:
affiliation: Miami VA Healthcare System, Miami, FL
name: Nancy G Klimas, BS MD
role: PRINCIPAL_INVESTIGATOR
References: