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

Primary Purpose

Huntington's Disease

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Creatine Monohydrate
Placebo
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Huntington's Disease focused on measuring Huntington's disease, Creatine, Mitochondrial Dysfunction, Total Functional Capacity, UHDRS

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama
  • University of California, Irvine
  • University of California Davis
  • University of Connecticut
  • University of Florida (McKnight Brain Institute)
  • University of South Florida
  • Emory University School of Medicine
  • Georgia Regents University
  • Rush University Medical Center
  • Indiana University
  • University of Iowa
  • University of Kansas Medical Center
  • Hereditary Neurological Disease Center (HNDC)
  • University of Louisville
  • University of Maryland School of Medicine
  • Massachusetts General Hospital
  • University of Michigan
  • Struthers Parkinson's Center
  • Washington University School of Medicine
  • Nebraska Medical Center
  • Cooper University Hospital
  • Albany Medical College
  • North Shore-LIJ Health System
  • Columbia University Medical Center
  • University of Rochester
  • Duke University
  • Wake Forest University School of Medicine
  • University of Cincinnati
  • Cleveland Clinic
  • Ohio State University
  • University of Pennsylvania
  • University of Pittsburgh
  • Medical University of South Carolina
  • University of Tennessee Health Science Center
  • Baylor College of Medicine
  • University of Utah
  • University of Virginia Health System
  • Booth Gardner Parkinson's Care Center (Evergreen Healthcare)
  • Westmead Hospital
  • Neurodegenerative Disorders Research
  • University of Alberta Hospital
  • University of Alberta
  • Movement Disorder Clinic Deer Lodge Center
  • CHUM - Hopital Notre-Dame
  • University of Quebec Infant-Jesus Hospital (Centre Hospitalier Affilie)
  • Auckland City Hospital
  • New Zealand Brain Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

A

B

Arm Description

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

Randomized to receive placebo (up to 40 grams daily)

Outcomes

Primary Outcome Measures

Change in Total Functional Capacity
Study duration depends on each subject's calendar date of enrollment.

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.

Full Information

First Posted
July 8, 2008
Last Updated
February 10, 2016
Sponsor
Massachusetts General Hospital
Collaborators
University of Rochester, National Center for Complementary and Integrative Health (NCCIH)
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1. Study Identification

Unique Protocol Identification Number
NCT00712426
Brief Title
Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)
Acronym
CREST-E
Official Title
Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Terminated
Why Stopped
Results of an interim analysis showed that it was unlikely that creatine was effective in slowing loss of function in early symptomatic Huntington's Disease.
Study Start Date
September 2009 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
University of Rochester, National Center for Complementary and Integrative Health (NCCIH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington's Disease
Keywords
Huntington's disease, Creatine, Mitochondrial Dysfunction, Total Functional Capacity, UHDRS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
553 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Active Comparator
Arm Description
Randomized to receive creatine monohydrate (up to 40 grams daily)
Arm Title
B
Arm Type
Placebo Comparator
Arm Description
Randomized to receive placebo (up to 40 grams daily)
Intervention Type
Drug
Intervention Name(s)
Creatine Monohydrate
Other Intervention Name(s)
HD-02
Intervention Description
Up to 40 grams daily, powder form creatine monohydrate, taken for the trial duration
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Dextrose
Intervention Description
Up to 40 grams daily, powder form placebo (inactive substance), taken for the trial duration
Primary Outcome Measure Information:
Title
Change in Total Functional Capacity
Description
Study duration depends on each subject's calendar date of enrollment.
Time Frame
Minimum 12 months up to 48 months
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven M Hersch, MD, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Giovanni Schifitto, MD
Organizational Affiliation
University of Rochester Clinical Trial Coordination Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Diana Rosas, MD, MS
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of California, Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
University of California Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Connecticut
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030
Country
United States
Facility Name
University of Florida (McKnight Brain Institute)
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Georgia Regents University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Hereditary Neurological Disease Center (HNDC)
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67206
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Maryland School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Struthers Parkinson's Center
City
Golden Valley
State/Province
Minnesota
ZIP/Postal Code
55427
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Cooper University Hospital
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Facility Name
Albany Medical College
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
North Shore-LIJ Health System
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14618
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Wake Forest University School of Medicine
City
Winston Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15260
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
University of Tennessee Health Science Center
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38163
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
University of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Booth Gardner Parkinson's Care Center (Evergreen Healthcare)
City
Kirkland
State/Province
Washington
ZIP/Postal Code
98034
Country
United States
Facility Name
Westmead Hospital
City
Wentworthville
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Neurodegenerative Disorders Research
City
Subiaco
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
Movement Disorder Clinic Deer Lodge Center
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3J 2H7
Country
Canada
Facility Name
CHUM - Hopital Notre-Dame
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
University of Quebec Infant-Jesus Hospital (Centre Hospitalier Affilie)
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1J 1Z4
Country
Canada
Facility Name
Auckland City Hospital
City
Auckland
ZIP/Postal Code
1142
Country
New Zealand
Facility Name
New Zealand Brain Research Institute
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand

12. IPD Sharing Statement

Citations:
PubMed Identifier
20460152
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.
Results Reference
background
PubMed Identifier
16434666
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.
Results Reference
background
PubMed Identifier
16055197
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.
Results Reference
background
PubMed Identifier
12787055
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.
Results Reference
background
PubMed Identifier
11447996
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.
Results Reference
background
PubMed Identifier
10844007
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.
Results Reference
background
PubMed Identifier
35747889
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.
Results Reference
derived
PubMed Identifier
30103342
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.
Results Reference
derived
PubMed Identifier
28701493
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.
Results Reference
derived

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

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