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

NCT ID: NCT00712426

Last Updated: 2016-03-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

553 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-30

Study Completion Date

2015-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Huntington's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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A

Randomized to receive creatine monohydrate (up to 40 grams daily)

Group Type ACTIVE_COMPARATOR

Creatine Monohydrate

Intervention Type DRUG

Up to 40 grams daily, powder form creatine monohydrate, taken for the trial duration

B

Randomized to receive placebo (up to 40 grams daily)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Up to 40 grams daily, powder form placebo (inactive substance), taken for the trial duration

Interventions

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Creatine Monohydrate

Up to 40 grams daily, powder form creatine monohydrate, taken for the trial duration

Intervention Type DRUG

Placebo

Up to 40 grams daily, powder form placebo (inactive substance), taken for the trial duration

Intervention Type DRUG

Other Intervention Names

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HD-02 Dextrose

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Rochester

OTHER

Sponsor Role collaborator

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Steven M. Hersch

Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Steven M Hersch, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Giovanni Schifitto, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester Clinical Trial Coordination Center

Diana Rosas, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

University of California, Irvine

Irvine, California, United States

Site Status

University of California Davis

Sacramento, California, United States

Site Status

University of Connecticut

Farmington, Connecticut, United States

Site Status

University of Florida (McKnight Brain Institute)

Gainesville, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

Georgia Regents University

Augusta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Hereditary Neurological Disease Center (HNDC)

Wichita, Kansas, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

University of Maryland School of Medicine

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Struthers Parkinson's Center

Golden Valley, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Cooper University Hospital

Camden, New Jersey, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

North Shore-LIJ Health System

Manhasset, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of Tennessee Health Science Center

Memphis, Tennessee, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

Booth Gardner Parkinson's Care Center (Evergreen Healthcare)

Kirkland, Washington, United States

Site Status

Westmead Hospital

Wentworthville, New South Wales, Australia

Site Status

Neurodegenerative Disorders Research

Subiaco, Western Australia, Australia

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

University of Alberta

Edmonton, Alberta, Canada

Site Status

Movement Disorder Clinic Deer Lodge Center

Winnipeg, Manitoba, Canada

Site Status

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

Site Status

University of Quebec Infant-Jesus Hospital (Centre Hospitalier Affilie)

Québec, Quebec, Canada

Site Status

Auckland City Hospital

Auckland, , New Zealand

Site Status

New Zealand Brain Research Institute

Christchurch, , New Zealand

Site Status

Countries

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United States Australia Canada New Zealand

References

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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.

Reference Type BACKGROUND
PMID: 20460152 (View on PubMed)

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. doi: 10.1212/01.wnl.0000194318.74946.b6.

Reference Type BACKGROUND
PMID: 16434666 (View on PubMed)

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. doi: 10.1016/j.pharmthera.2005.04.008. Epub 2005 Aug 1.

Reference Type BACKGROUND
PMID: 16055197 (View on PubMed)

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. doi: 10.1046/j.1471-4159.2003.01706.x.

Reference Type BACKGROUND
PMID: 12787055 (View on PubMed)

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. doi: 10.1006/nbdi.2001.0406.

Reference Type BACKGROUND
PMID: 11447996 (View on PubMed)

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. doi: 10.1523/JNEUROSCI.20-12-04389.2000.

Reference Type BACKGROUND
PMID: 10844007 (View on PubMed)

McGarry A, Auinger P, Kieburtz KD, Bredlau AL, Hersch SM, Rosas HD. Suicidality Risk Factors Across the CARE-HD, 2CARE, and CREST-E Clinical Trials in Huntington Disease. Neurol Clin Pract. 2022 Apr;12(2):131-138. doi: 10.1212/CPJ.0000000000001161.

Reference Type DERIVED
PMID: 35747889 (View on PubMed)

Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: August 2018. J Huntingtons Dis. 2018;7(3):279-286. doi: 10.3233/JHD-189003.

Reference Type DERIVED
PMID: 30103342 (View on PubMed)

Hersch SM, Schifitto G, Oakes D, Bredlau AL, Meyers CM, Nahin R, Rosas HD; Huntington Study Group CREST-E Investigators and Coordinators. The CREST-E study of creatine for Huntington disease: A randomized controlled trial. Neurology. 2017 Aug 8;89(6):594-601. doi: 10.1212/WNL.0000000000004209. Epub 2017 Jul 12.

Reference Type DERIVED
PMID: 28701493 (View on PubMed)

Other Identifiers

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U01AT000613

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2007P000827

Identifier Type: -

Identifier Source: org_study_id

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