Huntington Disease
Conditions
Brief summary
The purpose of this research study is to study the safety and efficacy of fenofibrate, an FDA-approved drug for high cholesterol and/or elevated triglycerides (fats), as a treatment for Huntington's disease (HD). Subjects who meet the entry criteria will be randomized (3:1) to either 145mg of fenofibrate or placebo.
Interventions
DRUGFenofibrate
145mg of fenofibrate
DRUGPlacebo
Placebo
Sponsors
University of California, Irvine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* An adult of either sex, ages 25-85 inclusive, * Have proficiency with written and spoken English and corrected vision or hearing to complete the cognitive testing, * Are able to give informed consent, * Have good overall health status with no known problems anticipated over the course of the trial, * Have a diagnosis of HD supported by positive gene test within the past 6 months.
Exclusion criteria
* Other major neurological disease \[e.g., multiple sclerosis, parkinson's disease, cortical stroke, etc\] * Clinically significant hepatic or renal disease, * Current or recent (\< 1 month) use of dopamine blocking agents such as tetrabenazine, anticonvulsants, neuroleptics, HAART, antiemetics, and antipsychotics for any reason, * Current use of Warfarin (Coumadin). Enrollment in another investigational drug study within the prior three months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in PGC-1alpha RNA Expression | Baseline compared to 3 and 6 months. | Change in PGC-1alpha RNA expression from Baseline, Month 3 and Month 6 |
| Change in PGC-1alpha Protein Abundance. | Baseline compared to 3 and 6 months. | Mean change in PGC-1alpha protein abundance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montreal Cognitive Assesment Score. | Baseline compared to 3 and 6 months. | Montreal Cognitive Assessment (total score range 0-30, higher score = less impairment) |
| Change in Fenofibric Acid Level. | Baseline to 3 and 6 months. | Change in Fenofibric acid abundance from Baseline to 3 and 6 months. |
| Change in Functional Assessment Scores | Baseline compared to 3 and 6 months. | Clinical Global Impression (CGI-I); (total score range 1-7 where higher score = greater impairment), and Unified Huntington Disease Rating Scale (UHDRS) Total Functional Capacity Assessment ( total score range 0-13, higher score = less impairment) |
| Changes in Unified Huntington Disease Rating Scale - Behavioral | Baseline, Month 3 and 6 months | Unified Huntington Disease Rating Scale (UHDRS) Behavioral Scale (total score range 0-100 where 100 = 100% independent) |
| Change in Unified Huntington Disease Rating Scale Motor Score. | Baseline and 6 months | Unified Huntington Disease Rating Scale (UHDRS) Motor (total score range 0-124 where higher score = greater impairment) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Fenofibrate: 145mg of fenofibrate | 9 |
| Placebo Placebo: Placebo | 1 |
| Total | 10 |
Baseline characteristics
| Characteristic | Active | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 1 Participants | 9 Participants |
| Age, Continuous | 54.8 years STANDARD_DEVIATION 9.9 | 49.9 years | 54.8 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 1 Participants | 10 Participants |
| Region of Enrollment United States | 9 participants | 1 participants | 10 participants |
| Sex: Female, Male Female | 5 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 5 Participants |
| UHDRS TFC | 9.78 units on a scale STANDARD_DEVIATION 2.44 | 8 units on a scale STANDARD_DEVIATION 0 | 9.6 units on a scale STANDARD_DEVIATION 2.37 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 1 |
| other Total, other adverse events | 0 / 9 | 0 / 1 |
| serious Total, serious adverse events | 0 / 9 | 0 / 1 |
Outcome results
Primary
Change in PGC-1alpha Protein Abundance.
Mean change in PGC-1alpha protein abundance.
Time frame: Baseline compared to 3 and 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Change in PGC-1alpha Protein Abundance. | Month 3 | 0.2609123 Log 2 fold change | Standard Deviation 1.031904 |
| Active | Change in PGC-1alpha Protein Abundance. | Month 6 | 0.02375246 Log 2 fold change | Standard Deviation 0.9096516 |
| Placebo | Change in PGC-1alpha Protein Abundance. | Month 3 | -0.02029792 Log 2 fold change | — |
| Placebo | Change in PGC-1alpha Protein Abundance. | Month 6 | 0.3185422 Log 2 fold change | — |
Primary
Change in PGC-1alpha RNA Expression
Change in PGC-1alpha RNA expression from Baseline, Month 3 and Month 6
Time frame: Baseline compared to 3 and 6 months.
Population: Fenofibrate vs placebo
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Change in PGC-1alpha RNA Expression | Month 3 | -0.02190716 Log 2 fold change | Standard Deviation 0.9017336 |
| Active | Change in PGC-1alpha RNA Expression | Month 6 | 0.07414876 Log 2 fold change | Standard Deviation 0.4723322 |
| Placebo | Change in PGC-1alpha RNA Expression | Month 3 | 0.3160562 Log 2 fold change | — |
| Placebo | Change in PGC-1alpha RNA Expression | Month 6 | 0.4800263 Log 2 fold change | — |
Secondary
Change in Fenofibric Acid Level.
Change in Fenofibric acid abundance from Baseline to 3 and 6 months.
Time frame: Baseline to 3 and 6 months.
Population: Fenofibrate vs placebo
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Change in Fenofibric Acid Level. | Baseline | 64 Ng/ml | Standard Deviation 117.48 |
| Active | Change in Fenofibric Acid Level. | Month 3 | 9037 Ng/ml | Standard Deviation 7114.1 |
| Active | Change in Fenofibric Acid Level. | Month 6 | 10905 Ng/ml | Standard Deviation 5900.77 |
| Placebo | Change in Fenofibric Acid Level. | Baseline | 5 Ng/ml | Standard Deviation 0 |
| Placebo | Change in Fenofibric Acid Level. | Month 3 | 10 Ng/ml | Standard Deviation 0 |
| Placebo | Change in Fenofibric Acid Level. | Month 6 | 19 Ng/ml | Standard Deviation 0 |
Secondary
Change in Functional Assessment Scores
Clinical Global Impression (CGI-I); (total score range 1-7 where higher score = greater impairment), and Unified Huntington Disease Rating Scale (UHDRS) Total Functional Capacity Assessment ( total score range 0-13, higher score = less impairment)
Time frame: Baseline compared to 3 and 6 months.
Population: Change in functional assessment scores from baseline, month 3 to month 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Change in Functional Assessment Scores | Baseline | 3.222 score on a scale | Standard Deviation 1.09 |
| Active | Change in Functional Assessment Scores | Month 3 | 3.571 score on a scale | Standard Deviation 0.787 |
| Active | Change in Functional Assessment Scores | Month 6 | 3.571 score on a scale | Standard Deviation 0.787 |
| Placebo | Change in Functional Assessment Scores | Baseline | 3 score on a scale | — |
| Placebo | Change in Functional Assessment Scores | Month 3 | 3 score on a scale | — |
| Placebo | Change in Functional Assessment Scores | Month 6 | 3 score on a scale | — |
Secondary
Change in Montreal Cognitive Assesment Score.
Montreal Cognitive Assessment (total score range 0-30, higher score = less impairment)
Time frame: Baseline compared to 3 and 6 months.
Population: Changes in cognition scores from baseline to month 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Change in Montreal Cognitive Assesment Score. | Baseline | 24.222 score on a scale | Standard Deviation 3.701 |
| Active | Change in Montreal Cognitive Assesment Score. | Month 3 | 25.778 score on a scale | Standard Deviation 3.866 |
| Active | Change in Montreal Cognitive Assesment Score. | Month 6 | 25.667 score on a scale | Standard Deviation 4.093 |
| Placebo | Change in Montreal Cognitive Assesment Score. | Baseline | 18 score on a scale | — |
| Placebo | Change in Montreal Cognitive Assesment Score. | Month 3 | 16 score on a scale | — |
| Placebo | Change in Montreal Cognitive Assesment Score. | Month 6 | 22 score on a scale | — |
Secondary
Change in Unified Huntington Disease Rating Scale Motor Score.
Unified Huntington Disease Rating Scale (UHDRS) Motor (total score range 0-124 where higher score = greater impairment)
Time frame: Baseline and 6 months
Population: Fenofibrate vs placebo. Change in motor scores from baseline to month 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Change in Unified Huntington Disease Rating Scale Motor Score. | Baseline | 19.56 score on a scale | Standard Deviation 11.87 |
| Active | Change in Unified Huntington Disease Rating Scale Motor Score. | Month 6 | 21.22 score on a scale | Standard Deviation 17.22 |
| Placebo | Change in Unified Huntington Disease Rating Scale Motor Score. | Baseline | 34 score on a scale | Standard Deviation 0 |
| Placebo | Change in Unified Huntington Disease Rating Scale Motor Score. | Month 6 | 27 score on a scale | Standard Deviation 0 |
Secondary
Changes in Unified Huntington Disease Rating Scale - Behavioral
Unified Huntington Disease Rating Scale (UHDRS) Behavioral Scale (total score range 0-100 where 100 = 100% independent)
Time frame: Baseline, Month 3 and 6 months
Population: Changes in independence assessment scores from baseline, month 3 to month 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active | Changes in Unified Huntington Disease Rating Scale - Behavioral | Baseline | 9.778 score on a scale | Standard Deviation 2.438 |
| Active | Changes in Unified Huntington Disease Rating Scale - Behavioral | Month 3 | 8.333 score on a scale | Standard Deviation 3.674 |
| Active | Changes in Unified Huntington Disease Rating Scale - Behavioral | Month 6 | 8.444 score on a scale | Standard Deviation 3.575 |
| Placebo | Changes in Unified Huntington Disease Rating Scale - Behavioral | Baseline | 8 score on a scale | — |
| Placebo | Changes in Unified Huntington Disease Rating Scale - Behavioral | Month 3 | 9 score on a scale | — |
| Placebo | Changes in Unified Huntington Disease Rating Scale - Behavioral | Month 6 | 8 score on a scale | — |