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

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

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).

Study Overview

• Status: Completed
• Conditions: Huntington's Disease
• Intervention / Treatment: Drug: CoQ10

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis
  • Colorado
    • Englewood, Colorado, United States, 80120
      • Colorado Neurological Institute
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Wichita, Kansas, United States, 67206
      • Hereditary Neurological Disease Centre (HNDC)
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Rochester, New York, United States, 14618
      • University of Rochester
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 600 mg per day of 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.	Drug: CoQ10; 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.; Other Names: -Ubiquinone; -coenzyme Q10
EXPERIMENTAL: 1200 mg per day of 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.	Drug: CoQ10; 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.; Other Names: -Ubiquinone; -coenzyme Q10
EXPERIMENTAL: 2400 mg per day of 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.	Drug: CoQ10; 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.; Other Names: -Ubiquinone; -coenzyme Q10

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Christopher A Ross, MD, PhD, Johns Hopkins University; Principal Investigator: Kevin M Biglan, MD, MPH, University of Rochester

Publications and helpful links

Helpful Links

• Huntington Study Group

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (ACTUAL): March 1, 2012
• Study Completion (ACTUAL): March 1, 2012

Study Registration Dates

• First Submitted: June 9, 2009
• First Submitted That Met QC Criteria: June 12, 2009
• First Posted (ESTIMATE): June 15, 2009

Study Record Updates

• Last Update Posted (ACTUAL): September 25, 2017
• Last Update Submitted That Met QC Criteria: August 25, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease; Physiological Effects of Drugs; Micronutrients; Vitamins; Coenzyme Q10; Ubiquinone
• Other Study ID Numbers: PREQUEL-01.00; NIH grant: 1 R01 NS060118-01A1