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

Overview

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.

Full Title of Study: “Creatine Safety, Tolerability, & Efficacy in Huntington’s Disease (CREST-E)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 2014

Interventions

  • Drug: Creatine Monohydrate
    • Up to 40 grams daily, powder form creatine monohydrate, taken for the trial duration
  • Drug: Placebo
    • Up to 40 grams daily, powder form placebo (inactive substance), taken for the trial duration

Arms, Groups and Cohorts

  • 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)

Clinical Trial Outcome Measures

Primary Measures

  • Change in Total Functional Capacity
    • Time Frame: Minimum 12 months up to 48 months
    • Study duration depends on each subject’s calendar date of enrollment.

Secondary 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.
    • Time Frame: Duration of the trial

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Massachusetts General Hospital
  • Collaborator
    • University of Rochester
  • Provider of Information About this Clinical Study
    • Principal Investigator: Steven M. Hersch, Professor of Neurology – Massachusetts General Hospital
  • Overall Official(s)
    • Steven M Hersch, MD, PhD, Principal Investigator, Massachusetts General Hospital
    • Giovanni Schifitto, MD, Principal Investigator, University of Rochester Clinical Trial Coordination Center
    • Diana Rosas, MD, MS, Principal Investigator, Massachusetts General Hospital

References

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.

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