Study in PRE-manifest Huntington's Disease of Coenzyme Q10 (UbiquinonE) Leading to Preventive Trials (PREQUEL)

Study Overview
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Brief Summary
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To establish the tolerability of treatment with 600, 1200 or 2400 mg per day of coenzyme Q10 in pre-manifest participants carrying the CAGn expansion for Huntington's Disease (HD).

Detailed Description
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secondary objectives: To assess the change from baseline to 20 weeks on biomarkers of oxidative stress (8OHdG and 8OHrG) and DNA repair mechanisms (OGG1) in pre-manifest participants treated with 600, 1200 or 2400 mg per day of CoQ10. To assess the dose-response relationship between CoQ10 at dosages of 600, 1200 or 2400 mg per day and 8OHdG/8OHrG and OGG1. To assess the serum levels of CoQ10 at 600, 1200 or 2400 mg in pre-manifest participants and their relationship to 8OHdG/8OHrG and OGG1. To assess the feasibility of implementing a preventive therapeutic trial in a pre-manifest population. To assess the utility and stability of clinical measures of HD, social relations, behavior and employment in a pre-manifest sample enrolled in a treatment trial.

Official Title
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A Multi-Center, Double-Blind, Randomized, Parallel Group Tolerability Study of Coenzyme Q10 (UbiquinonE)in PRE-manifest Huntington's Disease

Conditions
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Huntington's Disease

Intervention / Treatment
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* Drug: CoQ10


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants will be positive for the CAGn expansion in the Huntingtin gene (>36 repeats) and be pre-manifest by virtue of scoring 3 or less on diagnostic confidence level (Question 17 of the UHDRS) Participants will have received genetic testing prior to enrollment through a standard pre-manifest testing protocol. 18 years of age or older. Concomitant medications are permitted with the exception of CoQ10, creatine > 5g/day and warfarin. Exclusion Criteria: History of intolerability to CoQ10. CoQ10 use within 60 days prior to randomization. Unstable medical or psychiatric illness; Substance abuse within one year of the baseline visit. Pregnancy, breastfeeding or lack of reliable contraception in women of childbearing age. Subjects with known allergy to FD&C #6 yellow food coloring.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 600 mg per day of CoQ10<br>All participants will start on a dosage of 600 mg/day of CoQ10 in divided doses, increasing weekly by 600 mg/day to a maximum dosage of 2400 mg/day at week 4. Dosage should be stable from week 4 until week 20. | Drug: CoQ10<br>* Capsules containing 300 mg of CoQ10 or matching placebo taken orally twice a day. All participant will start on a dosage of 600 mg/day in divided doses, increasing weekly by 600 mg/day to a maximum dosage of 2400 mg/day at week 4. Dosage should be stable from week 4 until week 20.<br>* Other names: -coenzyme Q10;|
| Experimental: 1200 mg per day of CoQ10<br>All participants will start on a dosage of 600 mg/day in divided doses, increasing weekly by 600 mg/day to a maximum dosage of 2400 mg/day at week 4. Dosage should be stable from week 4 until week 20. | Drug: CoQ10<br>* Capsules containing 300 mg of CoQ10 or matching placebo taken orally twice a day. All participant will start on a dosage of 600 mg/day in divided doses, increasing weekly by 600 mg/day to a maximum dosage of 2400 mg/day at week 4. Dosage should be stable from week 4 until week 20.<br>* Other names: -coenzyme Q10;|
| Experimental: 2400 mg per day of CoQ10<br>All participants will start on a dosage of 600 mg/day in divided doses, increasing weekly by 600 mg/day to a maximum dosage of 2400 mg/day at week 4. Dosage should be stable from week 4 until week 20. | Drug: CoQ10<br>* Capsules containing 300 mg of CoQ10 or matching placebo taken orally twice a day. All participant will start on a dosage of 600 mg/day in divided doses, increasing weekly by 600 mg/day to a maximum dosage of 2400 mg/day at week 4. Dosage should be stable from week 4 until week 20.<br>* Other names: -coenzyme Q10;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability as Assessed by Ability to Complete the Study on the Originally Randomized Treatment Assignment. | No dosage modifications, reported as a % | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 8OHdG Levels | ng/ml. Negative value signifies an decrease in 8OHdG levels | change from baseline to 20 weeks | 
| CoQ10 Levels | ng/ml | change from baseline to 20 weeks |