The objective of this study is to determine whether creatine slows disease progression in
subjects with amyotrophic lateral sclerosis (ALS). ALS is a progressive uniformly lethal
neurodegenerative disorder for which there is no known cure. Recent genetic and biochemical
studies implicate free radical toxicity, glutamate excitotoxicity and mitochondrial
dysfunction as possible causes of familial ALS (FALS) and sporadic ALS (SALS). It has been
hypothesized that in ALS there may be involvement of oxidative free radical damage and
impaired mitochondrial energy metabolism that could in turn lead to excitotoxic cell death.
Creatine, an agent that improves mitochondrial function, has been shown to be
neuroprotective in animal models of ALS and Huntington's disease.
This study is a double-blind, randomized, placebo-controlled trial of the safety and
efficacy of creatine in patients with ALS enrolled at sites distributed throughout the
United States, including Northeast ALS (NEALS) sites. The study will provide preliminary
data on the safety and efficacy of creatine in ALS. If creatine slows disease progression
in ALS and is well tolerated, a phase 3 study with survival as the primary outcome measure
will be initiated.
114 eligible subjects will be randomized to receive treatment for 6 months of (1) active
creatine or (2) placebo. After randomization, subjects will be followed prospectively for 6
months. The primary outcome measure for the study is the change in upper extremity motor
function after 6 months of experimental therapy as tested with the Tufts Quantitative
Neuromuscular Exam. Strength in eight arm muscles will be measured (bilateral shoulder and
elbow flexion and extension). Secondary outcome measures include grip strength, motor unit
number estimates (MUNE), the ALS functional rating score-revised (ALSFRS-R), and rate of
change of a well established biochemical marker of oxidative damage to DNA (8OH2'dG levels
in urine), and the safety and tolerability of creatine.
- FVC >=50%
- Abnormality in upper and/or lower extremity motor function
- Not pregnant
- Disease duration <5 years