Clinical Trial of Creatine in Amyotrophic Lateral Sclerosis
Status:
Completed
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
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.