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

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00920699
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Enrollment: 90
• Locations: 13
• Arms: 3
• Duration (Months): 24.9
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Huntington's Disease	Drug: CoQ10	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Double-Blind, Randomized, Parallel Group Tolerability Study of Coenzyme Q10 (UbiquinonE)in PRE-manifest Huntington's Disease
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 8OHdG Levels [change from baseline to 20 weeks]

   ng/ml. Negative value signifies an decrease in 8OHdG levels

2. CoQ10 Levels [change from baseline to 20 weeks]

   ng/ml

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis	Sacramento	California	United States	95817
2	Colorado Neurological Institute	Englewood	Colorado	United States	80120
3	University of Miami School of Medicine	Miami	Florida	United States	33136
4	Emory University School of Medicine	Atlanta	Georgia	United States	30329
5	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
6	University of Iowa	Iowa City	Iowa	United States	52242
7	Hereditary Neurological Disease Centre (HNDC)	Wichita	Kansas	United States	67206
8	Johns Hopkins University	Baltimore	Maryland	United States	21287
9	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
10	Washington University	Saint Louis	Missouri	United States	63110
11	Albany Medical College	Albany	New York	United States	12208
12	University of Rochester	Rochester	New York	United States	14618
13	Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• Johns Hopkins University
• 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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Huntington Study Group

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00920699
• Other Study ID Numbers: PREQUEL-01.00; NIH grant: 1 R01 NS060118-01A1
• First Posted: Jun 15, 2009
• Last Update Posted: Sep 25, 2017
• Last Verified: Aug 1, 2017

• Additional relevant MeSH terms: Huntington Disease; Ubiquinone; Coenzyme Q10

Study Results

Participant Flow

Arm/Group Title	600 mg Per Day of CoQ10	1200 mg Per Day of CoQ10	2400 mg Per Day of CoQ10
Arm/Group Description	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. 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.	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. 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.	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. 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.
Period Title: Overall Study
STARTED	29	30	32
COMPLETED	27	29	28
NOT COMPLETED	2	1	4

Baseline Characteristics

Arm/Group Title	600 mg Per Day of CoQ10	1200 mg Per Day of CoQ10	2400 mg Per Day of CoQ10	Total
Arm/Group Description	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. 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.	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. 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.	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. 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.	Total of all reporting groups
Overall Participants	29	29	32	90
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.2 (9.8)	39.3 (11.5)	39.8 (11.6)	39.5 (10.9)
Sex: Female, Male (Count of Participants)
Female	15 51.7%	16 55.2%	16 50%	47 52.2%
Male	14 48.3%	13 44.8%	16 50%	43 47.8%
Region of Enrollment (Count of Participants)
United States	29 100%	29 100%	32 100%	90 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	600 mg Per Day of CoQ10	1200 mg Per Day of CoQ10	2400 mg Per Day of CoQ10
Arm/Group Description	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. 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.	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. 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.	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. 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.
Measure Participants	29	29	32
Number [percentage of participants]	90.0 310.3%	93.1 321%	81.3 254.1%

2. Secondary Outcome

Title	8OHdG Levels
Description	ng/ml. Negative value signifies an decrease in 8OHdG levels
Time Frame	change from baseline to 20 weeks

Outcome Measure Data

Analysis Population Description

Lab data not available for all participants to compare baseline and 20 weeks

Arm/Group Title	600 mg Per Day of CoQ10	1200 mg Per Day of CoQ10	2400 mg Per Day of CoQ10
Arm/Group Description	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. 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.	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. 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.	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. 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.
Measure Participants	19	21	27
Mean (Standard Deviation) [ng/ml]	0.15 (3.26)	-1.56 (3.23)	0.55 (7.1)

3. Secondary Outcome

Title	CoQ10 Levels
Description	ng/ml
Time Frame	change from baseline to 20 weeks

Outcome Measure Data

Analysis Population Description

data was not available for all participants to compare baseline to 20 weeks

Arm/Group Title	600 mg Per Day of CoQ10	1200 mg Per Day of CoQ10	2400 mg Per Day of CoQ10
Arm/Group Description	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. 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.	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. 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.	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. 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.
Measure Participants	24	25	28
Mean (Standard Deviation) [ng/ml]	1.82 (1.78)	1.92 (1.66)	2.33 (1.38)

Adverse Events

Time Frame	up to 20 weeks
Arm/Group Title	600 mg Per Day of CoQ10		1200 mg Per Day of CoQ10		2400 mg Per Day of CoQ10
Arm/Group Description	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. 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.		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. 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.		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. 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.
All Cause Mortality
	600 mg Per Day of CoQ10		1200 mg Per Day of CoQ10		2400 mg Per Day of CoQ10
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/29 (0%)		0/32 (0%)
Serious Adverse Events
	600 mg Per Day of CoQ10		1200 mg Per Day of CoQ10		2400 mg Per Day of CoQ10
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/29 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	600 mg Per Day of CoQ10		1200 mg Per Day of CoQ10		2400 mg Per Day of CoQ10
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/29 (31%)		20/29 (69%)		16/32 (50%)
Gastrointestinal disorders
Diarrhea	2/29 (6.9%)	2	7/29 (24.1%)	7	4/32 (12.5%)	4
Abdominal discomfort/pain; dyspepsia	2/29 (6.9%)	2	4/29 (13.8%)	4	1/32 (3.1%)	1
Abdominal distension	1/29 (3.4%)	1	1/29 (3.4%)	1	1/32 (3.1%)	1
Flatulence	0/29 (0%)	0	2/29 (6.9%)	2	1/32 (3.1%)	1
Vomiting	1/29 (3.4%)	1	1/29 (3.4%)	1	1/32 (3.1%)	1
Musculoskeletal and connective tissue disorders
increase creatinine phosphokinase (blood)	2/29 (6.9%)	2	0/29 (0%)	0	1/32 (3.1%)	1
Nervous system disorders
Dizziness	1/29 (3.4%)	1	2/29 (6.9%)	2	1/32 (3.1%)	1
Headache	0/29 (0%)	0	1/29 (3.4%)	1	2/32 (6.3%)	2
Psychiatric disorders
Depression	0/29 (0%)	0	2/29 (6.9%)	2	1/32 (3.1%)	1
Renal and urinary disorders
Hematuria	0/29 (0%)	0	0/29 (0%)	0	3/32 (9.4%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.