Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E) - Full Text View

Sponsor:	Massachusetts General Hospital
Collaborators:	University of Rochester National Center for Complementary and Alternative Medicine (NCCAM)
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00712426

Purpose

Huntington's disease (HD) is a slowly progressive disorder that devastates the lives of those affected and their families. There are no treatments that slow the progression of HD, only mildly effective symptomatic therapies are available.Creatine monohydrate is considered a nutritional supplement. The purpose of CREST-E is to test whether high-dose creatine can slow the progressive functional decline that occurs in persons 18 years or older with early clinical features of HD over 3-years. The long-term safety, tolerability and effectiveness of up to 40 grams daily creatine compared to placebo is studied. A variety of biological processes are assessed for markers of disease activity or progression and creatine effects. Up to 60 research centers globally will enroll 650 subjects.

Condition	Intervention	Phase
Huntington's Disease	Drug: Creatine Monohydrate (HD-02) Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)

Resource links provided by NLM:

Genetics Home Reference related topics: chorea-acanthocytosis familial paroxysmal nonkinesigenic dyskinesia Huntington disease McLeod neuroacanthocytosis syndrome

MedlinePlus related topics: Huntington's Disease

Drug Information available for: Creatine Dextrose Creatine monohydrate

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

Change in total functional capacity [ Time Frame: Over 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical symptoms (changes in other UHDRS scores); safety (frequency of adverse events); tolerability (proportion of subjects completing study at assigned dosage level), quality of life, other biological markers. [ Time Frame: Duration of the trial ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	650
Study Start Date:	September 2009
Estimated Study Completion Date:	April 2016
Estimated Primary Completion Date:	April 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: A Randomized to receive creatine monohydrate (up to 40 grams daily)	Drug: Creatine Monohydrate (HD-02) Up to 40 grams daily, powder form creatine monohydrate taken for 36-months Other Name: HD-02
Placebo Comparator: B Randomized to receive placebo (up to 40 grams daily)	Drug: Placebo Up to 40 grams daily, powder form placebo (inactive substance), taken for 36 months Other Name: Dextrose

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female ages 18 or older.
Clinical features of HD AND confirmatory family history of HD; OR CAG repeat expansion greater or equal to 36.
Stage I or II of illness (TFC greater or equal to 7).
Ambulatory and not requiring skilled nursing care at the time of enrollment.
Must be capable of providing informed consent and complying with trial procedures.
Additional inclusion criteria apply.

Exclusion Criteria:

History of known sensitivity or intolerability to creatine monohydrate.
Exposure to any investigational drug within 30 days of randomization (Baseline visit).
Use of supplemental creatine at a dose greater than 10 grams within 30 days of randomization (Baseline visit).
Screening laboratory abnormalities that in the judgment of the investigator would jeopardize safe conduct of study.
Clinical evidence of unstable medical illness.
Clinical evidence of unstable psychiatric illness.
Additional exclusion criteria apply.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00712426

Contacts

Contact: Huntington Study Group

1-800-487-7671

Show 50 Study Locations

Sponsors and Collaborators

Massachusetts General Hospital

University of Rochester

National Center for Complementary and Alternative Medicine (NCCAM)

Investigators

Principal Investigator:	Steven M Hersch, MD, PhD	Massachusetts General Hospital
Principal Investigator:	Giovanni Schifitto, MD	University of Rochester Clinical Trial Coordination Center
Principal Investigator:	Diana Rosas, MD, MS	Massachusetts General Hospital

More Information

Additional Information:

Huntington Study Group (CREST-E Study) This link exits the ClinicalTrials.gov site

Publications:

Kim J, Amante DJ, Moody JP, Edgerly CK, Bordiuk OL, Smith K, Matson SA, Matson WR, Scherzer CR, Rosas HD, Hersch SM, Ferrante RJ. Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease. Biochim Biophys Acta. 2010 Jul-Aug;1802(7-8):673-81. Epub 2010 May 9.

Hersch SM, Gevorkian S, Marder K, Moskowitz C, Feigin A, Cox M, Como P, Zimmerman C, Lin M, Zhang L, Ulug AM, Beal MF, Matson W, Bogdanov M, Ebbel E, Zaleta A, Kaneko Y, Jenkins B, Hevelone N, Zhang H, Yu H, Schoenfeld D, Ferrante R, Rosas HD. Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2'dG. Neurology. 2006 Jan 24;66(2):250-2.

Ryu H, Rosas HD, Hersch SM, Ferrante RJ. The therapeutic role of creatine in Huntington's disease. Pharmacol Ther. 2005 Nov;108(2):193-207. Epub 2005 Aug 1. Review.

Dedeoglu A, Kubilus JK, Yang L, Ferrante KL, Hersch SM, Beal MF, Ferrante RJ. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J Neurochem. 2003 Jun;85(6):1359-67.

Andreassen OA, Dedeoglu A, Ferrante RJ, Jenkins BG, Ferrante KL, Thomas M, Friedlich A, Browne SE, Schilling G, Borchelt DR, Hersch SM, Ross CA, Beal MF. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol Dis. 2001 Jun;8(3):479-91.

Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S, Kubilus JK, Kaddurah-Daouk R, Hersch SM, Beal MF. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci. 2000 Jun 15;20(12):4389-97.

Responsible Party:	Steven M. Hersch, MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00712426 History of Changes
Other Study ID Numbers:	2007P000827, U01AT000613
Study First Received:	July 8, 2008
Last Updated:	July 19, 2011
Health Authority:	United States: Federal Government; United States: Food and Drug Administration; Canada: Canadian Institutes of Health Research; Canada: Ethics Review Committee; Canada: Health Canada; Canada: Ministry of Health & Long Term Care, Ontario; Australia: Department of Health and Ageing Therapeutic Goods Administration; Australia: Human Research Ethics Committee; Australia: National Health and Medical Research Council; New Zealand: Food Safety Authority; New Zealand: Health Research Council; New Zealand: Health and Disability Ethics Committees; New Zealand: Institutional Review Board; New Zealand: Medsafe

Keywords provided by Massachusetts General Hospital:

Huntington's disease
Creatine
Mitochondrial Dysfunction
Total Functional Capacity
UHDRS

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 February 12, 2012