Premanifest Huntington's Disease Extension Study II: Creatine Safety & Tolerability (Pre-CREST-2X)
The purpose of this clinical trial is to extend the Pre-Crest-X study to further assess the long-term safety and tolerability of up to 30 grams daily creatine in individuals at-risk for Huntington's Disease (HD) and to assess whether biomarkers responsive to creatine in symptomatic individuals are informative in premanifest individuals over a longer duration.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Premanifest Huntington's Disease Extension Study II: Creatine Safety & Tolerability|
- Safety [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]Frequency of adverse events
- Tolerability [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]Proportion of subjects completing the extension study at given dose level
- Clinical measures [ Time Frame: 24 months ] [ Designated as safety issue: No ]Components of the UHDRS (Unified Huntington Disease Rating Scale)
- Biological Markers of Disease Progression [ Time Frame: 24 months ] [ Designated as safety issue: No ]Biological indicators that creatine treatment might affect the progression of HD: plasma levels of creatine, serum levels of 8OH2'dG and 8OHG, magnetic resonance imaging (MRI), morphometric neuroimaging (biomarker of neurodegeneration), metabolomic profiling, and gene expression analysis to assess transcriptional effects of HD and creatine therapy.
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||March 2013|
|Estimated Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
Drug: Creatine monohydrate
Extensive evidence exists that neurodegeneration begins many years before HD can be diagnosed clinically. Therefore, it is most desirable to begin a neuroprotective therapy before or during this premanifest period with the aim of delaying onset, as well as slowing functional decline. Cellular energy depletion is present early in HD and can be ameliorated by creatine, which helps regenerate cellular ATP. Preclinical evidence for creatine's potential neuroprotective effects in animal models of HD has been well-documented. Before the clinical efficacy of creatine can be tested in premanifest HD, its long-term safety and tolerability must be assessed in these individuals and its ability to favorably modify biomarkers of HD should also be confirmed. This extension trial will continue to follow eligible individuals who completed the Pre-CREST-X extension study on open-label creatine (up to 30 grams daily) for long term safety and tolerability for an additional 24 months. Other biological and imaging biomarkers of disease progression and potential response to treatment will also be assessed.
|United States, Massachusetts|
|Massachusetts General Hospital|
|Charlestown, Massachusetts, United States, 02129|
|Principal Investigator:||Diana Rosas, MD, MS||Massachusetts General Hospital|