Huntington's Disease
Conditions
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.
Interventions
DRUGCoQ10
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.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability as Assessed by Ability to Complete the Study on the Originally Randomized Treatment Assignment. | 20 weeks | No dosage modifications, reported as a % |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 8OHdG Levels | change from baseline to 20 weeks | ng/ml. Negative value signifies an decrease in 8OHdG levels |
| CoQ10 Levels | change from baseline to 20 weeks | ng/ml |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 29 |
| 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.
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. | 29 |
| 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.
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. | 32 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 2 |
| Overall Study | no longer met eligibility | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | 600 mg Per Day of CoQ10 | 1200 mg Per Day of CoQ10 | 2400 mg Per Day of CoQ10 | Total |
|---|---|---|---|---|
| Age, Continuous | 39.2 years STANDARD_DEVIATION 9.8 | 39.3 years STANDARD_DEVIATION 11.5 | 39.8 years STANDARD_DEVIATION 11.6 | 39.5 years STANDARD_DEVIATION 10.9 |
| Region of Enrollment United States | 29 Participants | 29 Participants | 32 Participants | 90 Participants |
| Sex: Female, Male Female | 15 Participants | 16 Participants | 16 Participants | 47 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 16 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 | 0 / 32 |
| other Total, other adverse events | 9 / 29 | 20 / 29 | 16 / 32 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 | 0 / 32 |
Outcome results
Primary
Tolerability as Assessed by Ability to Complete the Study on the Originally Randomized Treatment Assignment.
No dosage modifications, reported as a %
Time frame: 20 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 600 mg Per Day of CoQ10 | Tolerability as Assessed by Ability to Complete the Study on the Originally Randomized Treatment Assignment. | 90.0 percentage of participants |
| 1200 mg Per Day of CoQ10 | Tolerability as Assessed by Ability to Complete the Study on the Originally Randomized Treatment Assignment. | 93.1 percentage of participants |
| 2400 mg Per Day of CoQ10 | Tolerability as Assessed by Ability to Complete the Study on the Originally Randomized Treatment Assignment. | 81.3 percentage of participants |
Secondary
8OHdG Levels
ng/ml. Negative value signifies an decrease in 8OHdG levels
Time frame: change from baseline to 20 weeks
Population: Lab data not available for all participants to compare baseline and 20 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 600 mg Per Day of CoQ10 | 8OHdG Levels | 0.15 ng/ml | Standard Deviation 3.26 |
| 1200 mg Per Day of CoQ10 | 8OHdG Levels | -1.56 ng/ml | Standard Deviation 3.23 |
| 2400 mg Per Day of CoQ10 | 8OHdG Levels | 0.55 ng/ml | Standard Deviation 7.1 |
Secondary
CoQ10 Levels
ng/ml
Time frame: change from baseline to 20 weeks
Population: data was not available for all participants to compare baseline to 20 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 600 mg Per Day of CoQ10 | CoQ10 Levels | 1.82 ng/ml | Standard Deviation 1.78 |
| 1200 mg Per Day of CoQ10 | CoQ10 Levels | 1.92 ng/ml | Standard Deviation 1.66 |
| 2400 mg Per Day of CoQ10 | CoQ10 Levels | 2.33 ng/ml | Standard Deviation 1.38 |