Creatine monohydrate disappoints in Parkinson’s disease

By Eleanor McDermid, Senior medwireNews Reporter

Creatine monohydrate fails to live up to its early promise in patients with Parkinson’s disease (PD), show the results of the Long-term Study 1 (LS-1).

LS-1 enrolled 1741 patients, but was halted for futility after an interim analysis of the first 955 patients to attain 5 years of follow-up after being randomly assigned to receive creatine monohydrate (5 g, twice daily) or placebo.

The trial emerged from the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease (NET-PD) programme.

“Creatine was initially considered because of evidence that it plays an important role in cellular energy production, which may be impaired in Parkinson disease”, say Karl Kieburtz (University of Rochester, New York, USA) and study co-authors.

It was the only one of four compounds studied thought to have potential therapeutic effect after initial futility trials, and preclinical research suggested it would have a good safety profile.

“Yet despite the available preclinical and clinical evidence, creatine failed to slow the clinical progression of Parkinson disease as measured across 5 domains of Parkinson disease measured in the long-term clinical trial”, write the researchers in JAMA.

Outcomes were assessed with a global statistical test of five measures of PD progression. Among the 955 patients, the average score at 5 years was 2414 for those taking creatine and 2360 for those taking placebo, with higher scores indicating poorer outcomes. The difference between the two groups was not significant, so creatine neither helped nor harmed the patients.

All patients had been diagnosed with PD less than 5 years before enrolment into LS-1 and had been taking levodopa or a dopamine agonist for at least 90 days but no more than 2 years. Patients included in the preceding futility trials, on the other hand, were all untreated, which the researchers suggest could explain why creatine did not live up to the promise shown in those studies.

However, they stress the importance of testing treatments in patients receiving dopaminergic treatment, as this phase “is often associated with the most disability, and demonstrating a treatment effect during this phase would have a greater clinical and public health benefit.”

They also speculate that the creatine dose used may have been too low, although it was selected partly due to concerns of kidney consequences at higher doses.

More patients stopped taking creatine than placebo, despite no notable safety differences between the treatments. But analysis of patients who had continued treatment for at least 4 years gave similar results to the intention-to-treat analysis.

“These findings do not support the use of creatine monohydrate in such patients with Parkinson disease”, the team concludes.

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