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

Phase 2

Completed

Brief Summary: 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: secondary objectives:

1. 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.

2. To assess the dose-response relationship between CoQ10 at dosages of 600, 1200 or 2400 mg per day and 8OHdG/8OHrG and OGG1.

3. 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.

4. To assess the feasibility of implementing a preventive therapeutic trial in a pre-manifest population.

5. 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
1200 mg per day of CoQ10	CoQ10	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.
2400 mg per day of CoQ10	CoQ10	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.
600 mg per day of CoQ10	CoQ10	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.

Primary Outcome Measures

Name	Time	Method
Tolerability as Assessed by Ability to Complete the Study on the Originally Randomized Treatment Assignment.	20 weeks	No dosage modifications, reported as a %

Secondary Outcome Measures

Name	Time	Method
CoQ10 Levels	change from baseline to 20 weeks	ng/ml
8OHdG Levels	change from baseline to 20 weeks	ng/ml. Negative value signifies an decrease in 8OHdG levels

Locations (13): Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
University of California Davis
🇺🇸
Sacramento, California, United States
Colorado Neurological Institute
🇺🇸
Englewood, Colorado, United States
Emory University School of Medicine
🇺🇸
Atlanta, Georgia, United States
Indiana University School of Medicine
🇺🇸
Indianapolis, Indiana, United States
University of Iowa
🇺🇸
Iowa City, Iowa, United States
Hereditary Neurological Disease Centre (HNDC)
🇺🇸
Wichita, Kansas, United States
Washington University
🇺🇸
Saint Louis, Missouri, United States
Albany Medical College
🇺🇸
Albany, New York, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
University of Miami School of Medicine
🇺🇸
Miami, Florida, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States