Hiral Patel, PharmD. Candidate 2015, Mercer University College of Pharmacy
Currently there are no therapies that can stop or reverse the progression of Parkinson’s disease.1 The National Institute of Neurological Disorders and Stroke looked at four compounds for futility: creatine monohydrate, coenzyme Q10, GPI-1485, and minocycline. The only compound they found not to be futile was creatine monohydrate.2
|Title: Effects of Creatine Monohydrate on Clinical Progression in Patients with Parkinson’s Disease2|
|Design||Multicenter, double blind, parallel group, placebo-controlled, 1:1 randomized efficacy trial|
|Objective||To determine whether creatine monohydrate was more effective than placebo in slowing long-term decline in participants with Parkinson’s disease|
|Study groups||Placebo vs. creatine 10 g/day for a minimum of 5 years|
|Methods||Participants were randomized to creatine or placebo within each of the 45-blinded sites. Patients received 5 g creatine monohydrate or placebo dispensed in identical sachets, and mixed with food and taken twice a day. Participants were fewer than 5 years out from their Parkinson’s diagnosis and taking levodopa or a dopamine agonist for at least 90 days but not more than 2 years. Patients were still on their Parkinson’s drugs and changes in therapy were permitted.|
|Duration||Minimum of 5 years to a maximum follow up of 8 years||Primary Outcome Measure||Differences in clinical decline from baseline to 5 year follow up compared between the two treatment groups using a global statistic test|
|Baseline Characteristics||Mean age of patients in the placebo cohort was 61.5 years vs. 62.1 years in the creatine cohort. Males made up 64% of participants in the placebo cohort vs. 65% male in creatine cohort. Both cohorts had 90% non-Hispanic whites. Both cohorts were between 17 and 18 months since diagnosis, duration of symptoms were between 38 and 39 months, and received 8 months of symptomatic therapy. Patient’s levodopa equivalent daily dose (LEDD) was 376 mg for the placebo cohort as opposed to 391 mg in creatine cohort.||Results||The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of analysis.|
|Adverse Events||Common Adverse Events: Common Adverse Events: reduction in estimated glomerular filtration rate (eGFR) was reported based on modified body system as 37% in creatine cohort|
|Serious Adverse Events: death occurred in 5% of patients in creatine cohort|
|Percentage that Discontinued due to Adverse Events: creatine cohort had 0.8% of patients withdrawn due to eGFR less than 30 ml/min per 1.7 m2 or if creatinine more than doubled from baseline|
|Study Author Conclusions||Treatment with creatine monohydrate for at least 5 years, compared with placebo, did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in such patients with Parkinson’s disease.|
Despite the initial studies showing that creatine was not futile, creatine was not found to be beneficial for patients with Parkinson’s disease. In the future, other compounds that are shown to be promising need to be evaluated against other non-dopaminergic therapies. Another possibility that could have affected the trial was the dose of creatine used. However, due to unknown effects of creatine on the kidneys, the authors were not able to change the dosing. Overall, the findings of the study are not able to support the use of creatine monohydrate in patients with Parkinson’s disease.
1.NINDS Parkinson’s disease Information. National Institute of Neurological Disorders and Stroke website. Available at: http://www.ninds.nih.gov/disorders/Parkinson’ss_disease/Parkinson’ss_disease.htm. Accessed February 17, 2015.
2.Writing Group for the NINDS Exploratory Trials in Parkinson’s disease (NET-PD) Investigators. Effect of Creatine Monohydrate on Clinical Progression in Patients with Parkinson’s disease: A Randomized Clinical Trial. JAMA.2015;313(6):584-593. doi:10.1001/jama.2015.120.