Abstract
Objective: To investigate whether creatine administration could slow progressive functional decline in adults with early symptoms of Huntington disease.
Methods: We 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.
Results: At 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.
Conclusions: Our data do not support the use of creatine treatment for delaying functional decline in early manifest HD.
Clinicaltrials.gov 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.
GLOSSARY
- AE=
- adverse event;
- ATP=
- adenosine triphosphate;
- CREST-E=
- Creatine Safety, Tolerability & Efficacy in Huntington's Disease;
- DSMB=
- Data Safety Monitoring Board;
- FDA=
- Food and Drug Administration;
- HD=
- Huntington disease;
- ITT=
- intent-to-treat;
- TFC=
- total functional capacity;
- TMS=
- total motor score;
- UHDRS=
- Unified Huntington's Disease Rating Scale
Footnotes
Coinvestigators are listed at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was funded by NIH.
Supplemental data at Neurology.org
- Received December 15, 2016.
- Accepted in final form May 15, 2017.
- Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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