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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00712426




Registration number
NCT00712426
Ethics application status
Date submitted
8/07/2008
Date registered
10/07/2008
Date last updated
11/03/2016

Titles & IDs
Public title
Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)
Scientific title
Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)
Secondary ID [1] 0 0
U01AT000613
Secondary ID [2] 0 0
2007P000827
Universal Trial Number (UTN)
Trial acronym
CREST-E
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Huntington's Disease 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Creatine Monohydrate
Treatment: Drugs - Placebo

Active Comparator: A - Randomized to receive creatine monohydrate (up to 40 grams daily)

Placebo Comparator: B - Randomized to receive placebo (up to 40 grams daily)


Treatment: Drugs: Creatine Monohydrate
Up to 40 grams daily, powder form creatine monohydrate, taken for the trial duration

Treatment: Drugs: Placebo
Up to 40 grams daily, powder form placebo (inactive substance), taken for the trial duration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Total Functional Capacity
Timepoint [1] 0 0
Minimum 12 months up to 48 months
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Duration of the trial

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2015
Sample size
Target
Accrual to date
Final
553
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Wentworthville
Recruitment hospital [2] 0 0
Neurodegenerative Disorders Research - Subiaco
Recruitment postcode(s) [1] 0 0
2145 - Wentworthville
Recruitment postcode(s) [2] 0 0
6008 - Subiaco
Recruitment outside Australia
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United States of America
State/province [1] 0 0
Alabama
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United States of America
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California
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Connecticut
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Florida
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Georgia
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Illinois
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Indiana
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Iowa
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Kansas
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Kentucky
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Missouri
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Nebraska
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New Jersey
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New York
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North Carolina
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Ohio
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Utah
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Virginia
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United States of America
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Washington
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Canada
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Alberta
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Canada
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Manitoba
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Canada
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Quebec
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New Zealand
State/province [31] 0 0
Auckland
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New Zealand
State/province [32] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
Massachusetts General Hospital
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of Rochester
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Center for Complementary and Integrative Health (NCCIH)
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00712426
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Steven M Hersch, MD, PhD
Address 0 0
Massachusetts General Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00712426