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

NCT00712426 | Terminated Phase 3 DMC

• 2 other identifiers: 2007P000827U01AT000613
• Study Type: interventional
• Target: 553
• Locations: 4 countries
• Sites: 47

Brief 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.

Conditions

Huntington's Disease

Keywords

Huntington's disease; Creatine; Mitochondrial Dysfunction; Total Functional Capacity; UHDRS

Outcome Measures

Primary Outcomes (1)

• Change in Total Functional Capacity

  Study duration depends on each subject's calendar date of enrollment.

  Minimum 12 months up to 48 months

Secondary Outcomes (1)

• 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

Study Arms (2)

A

ACTIVE COMPARATOR

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

Drug: Creatine Monohydrate

B

PLACEBO COMPARATOR

Randomized to receive placebo (up to 40 grams daily)

Drug: Placebo

Interventions

Creatine Monohydrate DRUG

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

Also known as: HD-02

A

Placebo DRUG

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

Also known as: Dextrose

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• University of Rochester: collaborator
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (47)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

University of California Davis

Sacramento, California, 95817, United States

Location

University of Connecticut

Farmington, Connecticut, 06030, United States

Location

University of Florida (McKnight Brain Institute)

Gainesville, Florida, 32610, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

Georgia Regents University

Augusta, Georgia, 30329, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana University

Indianapolis, Indiana, 27157, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Hereditary Neurological Disease Center (HNDC)

Wichita, Kansas, 67206, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02129, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Struthers Parkinson's Center

Golden Valley, Minnesota, 55427, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Cooper University Hospital

Camden, New Jersey, 08103, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

North Shore-LIJ Health System

Manhasset, New York, 11030, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14618, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Booth Gardner Parkinson's Care Center (Evergreen Healthcare)

Kirkland, Washington, 98034, United States

Location

Westmead Hospital

Wentworthville, New South Wales, 2145, Australia

Location

Neurodegenerative Disorders Research

Subiaco, Western Australia, 6008, Australia

Location

University of Alberta Hospital

Edmonton, Alberta, T2N 4Z6, Canada

Location

University of Alberta

Edmonton, Alberta, T2N 4Z6, Canada

Location

Movement Disorder Clinic Deer Lodge Center

Winnipeg, Manitoba, R3J 2H7, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

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

Québec, Quebec, G1J 1Z4, Canada

Location

Auckland City Hospital

Auckland, 1142, New Zealand

Location

New Zealand Brain Research Institute

Christchurch, 8011, New Zealand

Location

Related Publications (9)

• 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.

  PMID: 20460152 BACKGROUND

• 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.

  PMID: 16434666 BACKGROUND

• 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.

  PMID: 16055197 BACKGROUND

• 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.

  PMID: 12787055 BACKGROUND

• 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.

  PMID: 11447996 BACKGROUND

• 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.

  PMID: 10844007 BACKGROUND

• 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.

  PMID: 35747889 DERIVED

• 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.

  PMID: 30103342 DERIVED

• 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.

  PMID: 28701493 DERIVED

Related Links

• Huntington Study Group (CREST-E Study)

MeSH Terms

Conditions

Huntington Disease; Mitochondrial Diseases

Interventions

Creatine; Glucose

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: July 8, 2008
• First Posted: July 10, 2008
• Study Start: September 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: January 1, 2015
• Last Updated: March 11, 2016

Record last verified: 2016-02

Locations

CA (5); US (38); AU (2); NZ (2)