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Creatine Safety and Tolerability in Premanifest HD: PRECREST

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Steven M. Hersch, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00592995
First received: December 28, 2007
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Huntington Disease
Drug: Creatine monohydrate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Creatine Safety and Tolerability in Premanifest HD: PRECREST

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Completion of Study (tolerability) [ Time Frame: 18 Months ] [ Designated as safety issue: Yes ]
    Tolerability (proportion of subjects completing study at given dose level)

  • Safety [ Time Frame: 18 Months ] [ Designated as safety issue: Yes ]
    Frequency of adverse events


Secondary Outcome Measures:
  • Pharmacokinetic and Pharmacodynamic biomarkers [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • UHDRS [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Brain Volumetric & Neurochemical Changes [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
  • Metabolomics & Gene Expression Biomarkers [ Time Frame: 18 Months ] [ Designated as safety issue: No ]

Enrollment: 64
Study Start Date: December 2007
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1 Drug: Placebo
10 to 30 grams daily
Active Comparator: 2 Drug: Creatine monohydrate
10 to 30 grams daily

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.

  Eligibility

Ages Eligible for Study:   26 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00592995

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

Publications:

Responsible Party: Steven M. Hersch, Professor of Neurology, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00592995     History of Changes
Other Study ID Numbers: 2006P001640, P01NS058793
Study First Received: December 28, 2007
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on November 20, 2014