Clinical trial NCT00712426: Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)
Official title: Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Huntington's Disease
Keywords: Huntington's disease
Creatine
Mitochondrial Dysfunction
Total Functional Capacity
UHDRS
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: University of Rochester
name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2008-07-10
Enrollment: 553
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Total Functional Capacity
timeFrame: Minimum 12 months up to 48 months
Secondary outcomes:
measure: 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.
timeFrame: Duration of the trial
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Farmington
country: United States
facility: University of Connecticut
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida (McKnight Brain Institute)
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: Hereditary Neurological Disease Center (HNDC)
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Golden Valley
country: United States
facility: Struthers Parkinson's Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Manhasset
country: United States
facility: North Shore-LIJ Health System
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: University of Tennessee Health Science Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Kirkland
country: United States
facility: Booth Gardner Parkinson's Care Center (Evergreen Healthcare)
state: Washington
city: Wentworthville
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Subiaco
country: Australia
facility: Neurodegenerative Disorders Research
state: Western Australia
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Winnipeg
country: Canada
facility: Movement Disorder Clinic Deer Lodge Center
state: Manitoba
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Quebec City
country: Canada
facility: University of Quebec Infant-Jesus Hospital (Centre Hospitalier Affilie)
state: Quebec
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: New Zealand Brain Research Institute
Study officials:
affiliation: Massachusetts General Hospital
name: Steven M Hersch, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester Clinical Trial Coordination Center
name: Giovanni Schifitto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Diana Rosas, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
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.
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. doi: 10.1212/01.wnl.0000194318.74946.b6.
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. doi: 10.1016/j.pharmthera.2005.04.008. Epub 2005 Aug 1.
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. doi: 10.1046/j.1471-4159.2003.01706.x.
citation: 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.
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. doi: 10.1523/JNEUROSCI.20-12-04389.2000.
citation: 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.
citation: 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.
citation: 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.