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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
Sponsor:
Information provided by (Responsible Party):
Steven M. Hersch, Massachusetts General Hospital

Study Description
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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.

Condition or disease Intervention/treatment Phase
Huntington Disease Drug: Creatine monohydrate Drug: Placebo Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Creatine Safety and Tolerability in Premanifest HD: PRECREST
Study Start Date : December 2007
Actual Primary Completion Date : September 2012
Actual Study Completion Date : September 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: 1 Drug: Placebo
10 to 30 grams daily
Active Comparator: 2 Drug: Creatine monohydrate
10 to 30 grams daily


Outcome Measures
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Primary Outcome Measures :
  1. Completion of Study (tolerability) [ Time Frame: 18 Months ]
    Tolerability (proportion of subjects completing study at given dose level)

  2. Safety [ Time Frame: 18 Months ]
    Frequency of adverse events


Secondary Outcome Measures :
  1. Pharmacokinetic and Pharmacodynamic biomarkers [ Time Frame: 18 months ]
  2. UHDRS [ Time Frame: 18 months ]
  3. Brain Volumetric & Neurochemical Changes [ Time Frame: 18 Months ]
  4. Metabolomics & Gene Expression Biomarkers [ Time Frame: 18 Months ]

Eligibility Criteria
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Ages Eligible for Study:   26 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00592995


Locations
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United States, Massachusetts
Massachusetts General Hospital
Charlestown, Massachusetts, United States, 02129
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Steven M Hersch, MD, PhD Massachusetts General Hospital
More Information
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Publications:

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Responsible Party: Steven M. Hersch, Professor of Neurology, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00592995    
Other Study ID Numbers: 2006P001640
P01NS058793 ( U.S. NIH Grant/Contract )
First Posted: January 14, 2008    Key Record Dates
Last Update Posted: February 10, 2014
Last Verified: January 2014
Additional relevant MeSH terms:
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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
Neurocognitive Disorders
Mental Disorders