Premanifest Huntington's Disease Extension Study II: Creatine Safety & Tolerability

Phase 2

Completed

• Conditions: Huntington's Disease
• Interventions: Drug: Creatine monohydrate

• Registration Number: NCT01411163
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

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.

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. 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.

Study Timeline

• Study Start: 2010-04
• Study First Submitted: 2011-08-04
• Study First Submitted QC: 2011-08-04
• Study First Posted: 2011-08-08
• Primary Completion: 2013-05
• Study Completion: 2013-05
• Status Verified: 2014-01
• Disposition First Submitted: 2014-01-10
• Disposition First Submitted QC: 2014-01-10
• Last Update Submitted: 2014-01-10
• Disposition First Posted: 2014-02-10
• Last Update Posted: 2014-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Individuals who have completed the Pre-CREST Study.
• Individuals capable of providing independent informed consent and complying with trial procedures.

Exclusion Criteria

-Clinical evidence of unstable medical or psychiatric illness in the investigator's judgment.

Additional eligibility criteria apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Creatine	Creatine monohydrate	-

Primary Outcome Measures

Name	Time	Method
Safety	24 months	Frequency of adverse events
Tolerability	24 months	Proportion of subjects completing the extension study at given dose level

Secondary Outcome Measures

Name	Time	Method
Clinical measures	24 months	Components of the UHDRS (Unified Huntington Disease Rating Scale)
Biological Markers of Disease Progression	24 months	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.

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Charlestown, Massachusetts, United States