Premanifest Huntington's Disease Extension Study II: Creatine Safety & Tolerability (Pre-CREST-2X)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Steven M. Hersch, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01411163
First received: August 4, 2011
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Huntington's Disease
Drug: Creatine monohydrate
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 24
Study Start Date: April 2010
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Creatine Drug: Creatine monohydrate
Up to 30 grams daily creatine monohydrate

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.

  Eligibility

Ages Eligible for Study:   26 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01411163

Locations
United States, Massachusetts
Massachusetts General Hospital
Charlestown, Massachusetts, United States, 02129
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Diana Rosas, MD, MS Massachusetts General Hospital
  More Information

Publications:

Responsible Party: Steven M. Hersch, Professor of Neurology, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01411163     History of Changes
Other Study ID Numbers: 2010P000511
Study First Received: August 4, 2011
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Federal Government

Keywords provided by Massachusetts General Hospital:
Premanifest
At-Risk
Huntington's Disease
HD

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on April 16, 2014