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

Huntington's Disease Clinical Trial

— CREST-E  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00712426
• Other study ID #: 2007P000827
• Secondary ID: U01AT000613
• Status: Terminated
• Phase: Phase 3
• First received: July 8, 2008
• Last updated: February 10, 2016
• Start date: September 2009
• Est. completion date: January 2015

Study information

• Verified date: February 2016
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug AdministrationCanada: Canadian Institutes of Health ResearchCanada: Ethics Review CommitteeCanada: Health CanadaCanada: Ministry of Health & Long Term Care, OntarioAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: Human Research Ethics CommitteeAustralia: National Health and Medical Research CouncilNew Zealand: Food Safety AuthorityNew Zealand: Health Research CouncilNew Zealand: Health and Disability Ethics CommitteesNew Zealand: Institutional Review BoardNew Zealand: Medsafe
• Study type: Interventional

Clinical Trial Summary

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. 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 50 active research centers globally will enroll 650 subjects.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 553
• Est. completion date: January 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female ages 18 or older.

• Clinical features of HD AND confirmatory family history of HD; OR Clinical features of HD AND 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Drug:
• Creatine Monohydrate
Up to 40 grams daily, powder form creatine monohydrate, taken for the trial duration
• Placebo
Up to 40 grams daily, powder form placebo (inactive substance), taken for the trial duration

Locations

Country	Name	City	State
Australia	Neurodegenerative Disorders Research	Subiaco	Western Australia
Australia	Westmead Hospital	Wentworthville	New South Wales
Canada	University of Alberta	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	University of Quebec Infant-Jesus Hospital (Centre Hospitalier Affilie)	Quebec City	Quebec
Canada	Movement Disorder Clinic Deer Lodge Center	Winnipeg	Manitoba
New Zealand	Auckland City Hospital	Auckland
New Zealand	New Zealand Brain Research Institute	Christchurch
United States	Albany Medical College	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Georgia Regents University	Augusta	Georgia
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cooper University Hospital	Camden	New Jersey
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Duke University	Durham	North Carolina
United States	University of Connecticut	Farmington	Connecticut
United States	University of Florida (McKnight Brain Institute)	Gainesville	Florida
United States	Struthers Parkinson's Center	Golden Valley	Minnesota
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	University of California, Irvine	Irvine	California
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Booth Gardner Parkinson's Care Center (Evergreen Healthcare)	Kirkland	Washington
United States	University of Louisville	Louisville	Kentucky
United States	North Shore-LIJ Health System	Manhasset	New York
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Rochester	Rochester	New York
United States	University of California Davis	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of South Florida	Tampa	Florida
United States	Hereditary Neurological Disease Center (HNDC)	Wichita	Kansas
United States	Wake Forest University School of Medicine	Winston Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Center for Complementary and Integrative Health (NCCIH), University of Rochester

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. doi: 10.1016/j.bbadis.2010.05.001. Epub 2010 May 9. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Total Functional Capacity	Study duration depends on each subject's calendar date of enrollment.	Minimum 12 months up to 48 months	No
Secondary	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.		Duration of the trial	Yes