Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)

Study Overview
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Brief Summary
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Huntington's disease (HD) is a slowly progressive disorder that devastates the lives of those affected and their families. There are no treatments that slow the progression of HD, only mildly effective symptomatic therapies are available.Creatine monohydrate is considered a nutritional supplement. The purpose of CREST-E is to test whether high-dose creatine can slow the progressive functional decline that occurs in persons 18 years or older with early clinical features of HD. The long-term safety, tolerability and effectiveness of up to 40 grams daily creatine compared to placebo is studied. A variety of biological processes are assessed for markers of disease activity or progression and creatine effects. Up to 50 active research centers globally will enroll 650 subjects.

Official Title
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Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)

Conditions
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Huntington's Disease

Intervention / Treatment
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* Drug: Creatine Monohydrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ages 18 or older. Clinical features of HD AND confirmatory family history of HD; OR Clinical features of HD AND CAG repeat expansion greater or equal to 36. Stage I or II of illness (TFC greater or equal to 7). Ambulatory and not requiring skilled nursing care at the time of enrollment. Must be capable of providing informed consent and complying with trial procedures. Additional inclusion criteria apply. Exclusion Criteria: History of known sensitivity or intolerability to creatine monohydrate. Exposure to any investigational drug within 30 days of randomization (Baseline visit). Use of supplemental creatine at a dose greater than 10 grams within 30 days of randomization (Baseline visit). Screening laboratory abnormalities that in the judgment of the investigator would jeopardize safe conduct of study. Clinical evidence of unstable medical illness. Clinical evidence of unstable psychiatric illness. Additional exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Randomized to receive creatine monohydrate (up to 40 grams daily) | Drug: Creatine Monohydrate<br>* Up to 40 grams daily, powder form creatine monohydrate, taken for the trial duration<br>* Other names: HD-02;|
| Placebo Comparator: B<br>Randomized to receive placebo (up to 40 grams daily) | Drug: Placebo<br>* Up to 40 grams daily, powder form placebo (inactive substance), taken for the trial duration<br>* Other names: Dextrose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Functional Capacity | Study duration depends on each subject's calendar date of enrollment. | Minimum 12 months up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical symptoms (changes in other UHDRS scores); safety (frequency of adverse events); tolerability (proportion of subjects completing study at assigned dosage level), quality of life, other biological markers. |  | Duration of the trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Huntington's disease, Creatine, Mitochondrial Dysfunction, Total Functional Capacity, UHDRS