NET-PD LS-1: creatine

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Karl Kieburtz, Barbara Tilley, Jordan Elm and the NINDS NET-PD investigators, at 45 sites in the US and Canada. JAMA, published online 10 February 2015.

What happened

In 2001 the US National Institute of Neurological Disorders and Stroke launched the Exploratory Trials in Parkinson Disease (NET-PD) programme. Short Phase 2 "futility" studies screened candidate drugs and asked only whether any looked too weak to be worth a big trial. Four were tested and none was ruled out (landmark 164); creatine monohydrate, a dietary supplement, went forward. Long-term Study 1 (LS-1; NCT00449865) enrolled 1,741 people with early (within 5 years of diagnosis), already-treated Parkinson's between March 2007 and May 2010 and randomised them to creatine 10 g a day or placebo, for a planned minimum of five years (maximum eight). At a planned interim analysis of the 955 people enrolled at least five years earlier (median follow-up 4 years), the combined measure of five outcomes (disability, thinking speed, quality of life, daily activities and walking) was no different (P = .45; mean summed ranks 2,414 on creatine vs 2,360 on placebo, higher being worse), and the trial was stopped for futility. There were no detectable differences in adverse events.

Why it moved us toward a cure

Creatine reached this trial by clearing the NET-PD futility screen (landmark 164, above). It is among the largest slowing trials in this catalogue and showed that a screening programme can still pick a dud. It adds to the case in dead ends for better patient selection and measures of progression (see PPMI). Compare QE3, a similar supplement trial a year earlier.

Outcome

Dead end. The investigators concluded the findings "do not support the use of creatine monohydrate in patients with Parkinson's disease."

Sources

• Kieburtz et al., JAMA 2015, DOI 10.1001/jama.2015.120
• PubMed 25668262: JAMA 2015;313(6):584-593 (abstract: design, dates, numbers)
• ClinicalTrials.gov NCT00449865 (1,741 enrolled; terminated for futility)
• Pharmaceutical Journal, 20 Feb 2015 (this page says "10 mg/day" and 955 participants, both apparently errors; the abstract gives 10 g/day and 1,741 enrolled, 955 in the interim analysis)
• Not yet verified: the NET-PD launch year (2001, per the Pharmaceutical Journal and an NIH-hosted review seen only in search results); the exact online date, 10 Feb 2015.