title: PRECREST: a phase II prevention and biomarker trial of creatine in at-risk Huntington disease.
abstract: OBJECTIVE
  To assess the safety and tolerability of high-dose creatine, the feasibility of enrolling premanifest and 50% at-risk subjects in a prevention trial, and the potential of cognitive, imaging, and blood markers.
  
  
  METHODS
  Sixty-four eligible consenting participants were randomly allocated (1:1) to 15 g twice daily of creatine monohydrate or placebo for a 6-month double-blind phase followed by a 12-month open-label extension. Subjects included premanifest (tested) and at-risk (not tested) individuals without clinical symptoms or signs of Huntington disease (HD). Primary outcomes were safety and tolerability. Exploratory endpoints included fine motor, visuospatial, and memory performance; structural and diffusion MRI; and selected blood markers.
  
  
  RESULTS
  Forty-seven HD carriers and 17 non-HD controls were enrolled. Fifteen discontinued treatment (2 assigned to placebo); all were followed for the entire study period. Primary analysis was by intent to treat. The most common adverse events were gastrointestinal. Neuroimaging demonstrated treatment-related slowing of cortical and striatal atrophy at 6 and 18 months.
  
  
  CONCLUSIONS
  We describe a design that preserves the autonomy of subjects not wanting genetic testing while including controls for assessing the specificity of treatment effects. Our results demonstrate the feasibility of prevention trials for HD and the safety of high-dose creatine, provide possible evidence of disease modification, support future studies of creatine, and illustrate the value of prodromal biomarkers.
  
  
  METHODS
  This study provides Class I evidence that high-dose creatine is safe and tolerable.
authors: From the Departments of Neurology (H.D.R., S.G., K.M., M.R., T.D.T., P.J.W., S.M.H.), Center for Neuro-imaging of Aging and Neurodegenerative Diseases (H.D.R., S.G., K.M., M.R., J.-P.C., T.D.T., P.J.W., D.H.S.), Athinoula A. Martinos Center for Biomedical Imaging (H.D.R., S.G., K.M., M.R., T.D.T., P.J.W., D.H.S.), and Radiology (H.D.R., M.R.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Biostatistics (G.D.), School of Public Health, Boston University, Boston; Harvard-MIT Division of Health Sciences and Technology (J.-P.C.), Cambridge; and Geriatric Research Education Clinical Center (W.M.), New England Veterans Administration, Bedford, MA.
authors: Herminia D
authors: HD
authors: Rosas
authors: Gheorghe
authors: G
authors: Doros
authors: Sona
authors: S
authors: Gevorkian
authors: Keith
authors: K
authors: Malarick
authors: Martin
authors: M
authors: Reuter
authors: Jean-Philippe
authors: JP
authors: Coutu
authors: Tyler D
authors: TD
authors: Triggs
authors: Paul J
authors: PJ
authors: Wilkens
authors: Wayne
authors: W
authors: Matson
authors: David H
authors: DH
authors: Salat
authors: Steven M
authors: SM
authors: Hersch
mesh_terms: D000328:Adult; D001284:Atrophy; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003072:Cognition Disorders / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D003401:Creatine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018592:Cross-Over Studies; D038524:Diffusion Magnetic Resonance Imaging; D004311:Double-Blind Method; D005240:Feasibility Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006816:Huntington Disease / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D062706:Prodromal Symptoms; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D003401:Creatine