A Phase III, Multi-Center, Double-Blind, Placebo Controlled, Randomized Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis

Twenty-one ALS patients were enrolled in a placebo controlled pilot study at the Carolinas Neuromuscular/ALS-MDA Center, The University of Texas Health Science Center at San Antonio and The University of New Mexico at Albuquerque. At all time points sampled over a nine month period, patients taking creatine monohydrate had either a significantly greater improvement in their strength or a more modest decline compared to the patients taking placebo. Overall analysis of variance is significant for both an effect of the drug (p=0.002) and time (p< 0.001).The pilot study also showed that quality of life, as measured by ALSFRS-R, correlated significantly with the observed changes in muscle strength (MVIC).

Phase III Study: The primary objective of this study is to determine whether treatment with creatine monohydrate results in an increase in muscle strength relative to placebo in patients with amyotrophic lateral sclerosis (ALS), after three months, and at the end of a nine-month treatment period.

The study is a Phase III, eight-center, double-blind, placebo-controlled, randomized clinical trial designed to evaluate the safety and efficacy of creatine monohydrate in patients fulfilling the eligibility criteria. The subjects (n=156) will be randomized in a 1:1 ratio to receive treatment of highly purified creatine monohydrate or placebo (Dextrose, USP) for nine months. The subjects will be administered 10 grams of creatine monohydrate per day for the first five days, and then 5 grams per day thereafter. Each subject will be followed for the nine-month treatment period.

The primary outcome measure for the study is change in upper extremity motor function after three weeks, and at the end of a nine-month treatment period as tested by MVIC. Strength in ten arm muscles will be measured (bilateral shoulder and elbow flexion/extension and grip).

Patient safety will be assured by ongoing review of reports of adverse events, clinical laboratory data, and measurement of vital signs. These tests include: measurement of MVIC and muscle fatigue, measurement of FVC, completion of ALSFRS-R and SF-12 quality of life instruments, review of potential adverse effects, determination of vital signs and weight, serum creatinine and BUN, and urine dipstick for protein.