Evidence map›Paper›PMID 28701493›Full record

Trial reportNeurology2017

The CREST-E study of creatine for Huntington disease: A randomized controlled trial.

Steven M Hersch, Giovanni Schifitto, David Oakes, Amy-Lee Bredlau, Catherine M Meyers, Richard Nahin, Herminia Diana Rosas, Huntington Study Group CREST-E Investigators and Coordinators

Registry-linked trialOpen access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00712426 (Creatine Safety, Tolerability, & Efficacy in Huntington's Disease), which is not on this map. Cited by 55 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 2 pooled it
4.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00712426 phase3terminatednot on this map

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

TypeinterventionalSponsorMassachusetts General HospitalRan2009 to 2015Enrolled553ConditionsHuntington's DiseaseArmsCreatine Monohydrate, Placebo
3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Steven M HerschFrom the Department of Neurology (S.M.H., H.D.R.), Massachusetts General Hospital and Harvard Medical School, Boston; Departments of Neurology and Biostatistics (G.S., D.O.), University of Rochester Medical Center, NY; Department of Pediatrics (A.-L.B.), Medical University of South Carolina, Charleston; and NIH (C.M.M., R.N.), National Center for Complementary and Integrative Health, Bethesda, MD. hersch@helix.mgh.harvard.edu.
Giovanni SchifittoFrom the Department of Neurology (S.M.H., H.D.R.), Massachusetts General Hospital and Harvard Medical School, Boston; Departments of Neurology and Biostatistics (G.S., D.O.), University of Rochester Medical Center, NY; Department of Pediatrics (A.-L.B.), Medical University of South Carolina, Charleston; and NIH (C.M.M., R.N.), National Center for Complementary and Integrative Health, Bethesda, MD.
David OakesFrom the Department of Neurology (S.M.H., H.D.R.), Massachusetts General Hospital and Harvard Medical School, Boston; Departments of Neurology and Biostatistics (G.S., D.O.), University of Rochester Medical Center, NY; Department of Pediatrics (A.-L.B.), Medical University of South Carolina, Charleston; and NIH (C.M.M., R.N.), National Center for Complementary and Integrative Health, Bethesda, MD.
Amy-Lee BredlauFrom the Department of Neurology (S.M.H., H.D.R.), Massachusetts General Hospital and Harvard Medical School, Boston; Departments of Neurology and Biostatistics (G.S., D.O.), University of Rochester Medical Center, NY; Department of Pediatrics (A.-L.B.), Medical University of South Carolina, Charleston; and NIH (C.M.M., R.N.), National Center for Complementary and Integrative Health, Bethesda, MD.
Catherine M MeyersFrom the Department of Neurology (S.M.H., H.D.R.), Massachusetts General Hospital and Harvard Medical School, Boston; Departments of Neurology and Biostatistics (G.S., D.O.), University of Rochester Medical Center, NY; Department of Pediatrics (A.-L.B.), Medical University of South Carolina, Charleston; and NIH (C.M.M., R.N.), National Center for Complementary and Integrative Health, Bethesda, MD.
Richard NahinFrom the Department of Neurology (S.M.H., H.D.R.), Massachusetts General Hospital and Harvard Medical School, Boston; Departments of Neurology and Biostatistics (G.S., D.O.), University of Rochester Medical Center, NY; Department of Pediatrics (A.-L.B.), Medical University of South Carolina, Charleston; and NIH (C.M.M., R.N.), National Center for Complementary and Integrative Health, Bethesda, MD.
Herminia Diana RosasFrom the Department of Neurology (S.M.H., H.D.R.), Massachusetts General Hospital and Harvard Medical School, Boston; Departments of Neurology and Biostatistics (G.S., D.O.), University of Rochester Medical Center, NY; Department of Pediatrics (A.-L.B.), Medical University of South Carolina, Charleston; and NIH (C.M.M., R.N.), National Center for Complementary and Integrative Health, Bethesda, MD.
Huntington Study Group CREST-E Investigators and Coordinators
Medical University of South Carolina · USUniversity of Rochester Medical Center · US

Funding

Creatine Safety, Tolerability, and Efficacy in Huntington's Disease: CREST-EU01AT000613 · NCCIH · MASSACHUSETTS GENERAL HOSPITAL · PI HERSCH, STEVEN M · 2007 to 2015
$12.9M
Neuroimaging Biomarkers for disease-modyfying therapies in Hintington's diseaseP01NS058793 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI HERSCH, STEVEN M · 2008 to 2012
$6.6M
Blood Level of Huntingtin: A Biomarker for Huntington's DiseaseU01NS071789 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI HERSCH, STEVEN M · 2010 to 2014
$3.4M
Creatine Safety and Efficacy in HD: Coordination and Statistical CenterU01AT008197 · NCCIH · UNIVERSITY OF ROCHESTER · PI SCHIFITTO, GIOVANNI · 2014 to 2016
$2.0M
NCCIH NIH HHS U01 AT000613NCCIH NIH HHS U01 AT008197NINDS NIH HHS P01 NS058793NINDS NIH HHS U01 NS071789
6 · The paper itself

Abstract

objectiveTo investigate whether creatine administration could slow progressive functional decline in adults with early symptoms of Huntington disease.

methodsWe conducted a multicenter, randomized, double-blind, placebo-controlled study of up to 40 g daily of creatine monohydrate in participants with stage I and II HD treated for up to 48 months. The primary outcome measure was the rate of change in total functional capacity (TFC) between baseline and end of follow-up. Secondary outcome measures included changes in additional clinical scores, tolerability, and quality of life. Safety was assessed by adverse events and laboratory studies.

resultsAt 46 sites in North America, Australia, and New Zealand, 553 participants were randomized to creatine (275) or placebo (278). The trial was designed to enroll 650 patients, but was halted for futility after the first interim analysis. The estimated rates of decline in the primary outcome measure (TFC) were 0.82 points per year for participants on creatine, 0.70 points per year for participants on placebo, favoring placebo (nominal 95% confidence limits -0.11 to 0.35). Adverse events, mainly gastrointestinal, were significantly more common in participants on creatine. Serious adverse events, including deaths, were more frequent in the placebo group. Subgroup analysis suggested that men and women may respond differently to creatine treatment.

conclusionsOur data do not support the use of creatine treatment for delaying functional decline in early manifest HD. CLINICALTRIALSGOV IDENTIFIER: NCT00712426. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with early symptomatic HD, creatine monohydrate is not beneficial for slowing functional decline.

Indexed as

AustraliaCreatineDisease ProgressionDouble-Blind MethodFemaleFollow-Up StudiesHumansHuntington DiseaseMaleMiddle AgedNeuroprotective AgentsNew ZealandNorth AmericaQuality of LifeTreatment OutcomeCreatineNeuroprotective Agents

Identifiers

PMID28701493
PMCPMC5562960
OpenAlexW2736236310

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.