Creatine Safety and Tolerability in Premanifest HD: PRECREST (PRECREST)
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ClinicalTrials.gov Identifier: NCT00592995 |
Recruitment Status :
Completed
First Posted : January 14, 2008
Last Update Posted : February 10, 2014
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Sponsor:
Massachusetts General Hospital
Information provided by (Responsible Party):
Steven M. Hersch, Massachusetts General Hospital
Tracking Information | ||||
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First Submitted Date ICMJE | December 28, 2007 | |||
First Posted Date ICMJE | January 14, 2008 | |||
Last Update Posted Date | February 10, 2014 | |||
Study Start Date ICMJE | December 2007 | |||
Actual Primary Completion Date | September 2012 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE |
completion of study (tolerability) [ Time Frame: 18 months ] | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Creatine Safety and Tolerability in Premanifest HD: PRECREST | |||
Official Title ICMJE | Creatine Safety and Tolerability in Premanifest HD: PRECREST | |||
Brief Summary | PRECREST is a two phase protocol for Huntington's disease in which 60 premanifest and at-risk subjects will first be randomized into a double blind placebo controlled dose titration study bringing them to 30 grams daily or their highest tolerated dose. This phase will establish the highest tolerable doses in premanifest HD and permit the detection of toxicity and intolerability with attribution to active compound versus placebo, and enable a dose response assessment of biomarkers. In the second phase, all subjects will enter a year long open-label treatment on 30 grams daily (or their highest dose) of creatine to assess long term exposure to high dose creatine and its long term impact on various biomarkers. | |||
Detailed Description | 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. A two phase protocol is proposed in which 60 premanifest and at-risk subjects will randomized into a double blind placebo controlled dose titration study bringing them to 30 grams daily or their highest tolerated dose. The placebo-controlled phase will permit the detection of toxicity and intolerability due to the active compound (creatine), and enable a dose response assessment of biomarkers. In the second phase, all subjects will enter a year long open-label treatment on 30 grams daily of creatine. This phase will maximize the subjects on active compound to promote recruitment and retention, to expand assessment of safety data on all subjects, and increase the power to detect and measure potential biological markers and any response to the active compound. The clinical impact of creatine will be assessed using the United Huntington's Disease Rating Scale. Safety and tolerability will be assessed by analyzing clinical and laboratory adverse events. Serum levels of creatine will be used to assess compliance and whether there is a relationship between bioavailability and response. 8OH2'dG and related markers will be assessed to determine whether creatine treatment can chronically suppress markers of energy depletion and oxidative injury and whether suppression correlates with slowing the progression of HD. Morphometric MRI will be used to determine whether creatine can slow brain atrophy in premanifest HD. This study will provide the pilot data needed to plan a future study to determine whether creatine can delay the onset or slow the progress of HD in premanifest individuals. | |||
Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 2 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Huntington Disease | |||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
64 | |||
Original Estimated Enrollment ICMJE |
75 | |||
Actual Study Completion Date ICMJE | September 2012 | |||
Actual Primary Completion Date | September 2012 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria: - Expansion positive or 50% at risk for HD and not diagnosed clinically Exclusion Criteria: - Unstable medical conditions Additional inclusion and exclusion criteria apply. |
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Sex/Gender ICMJE |
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Ages ICMJE | 26 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT00592995 | |||
Other Study ID Numbers ICMJE | 2006P001640 P01NS058793 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | Steven M. Hersch, Massachusetts General Hospital | |||
Original Responsible Party | Steven Hersch, Massachusetts General Hospital | |||
Current Study Sponsor ICMJE | Massachusetts General Hospital | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | Massachusetts General Hospital | |||
Verification Date | January 2014 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |