Clinical Trial of Creatine in Amyotrophic Lateral Sclerosis

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Creatinine

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ALS
• FVC >=50%
• Abnormality in upper and/or lower extremity motor function
• Not pregnant
• Disease duration <5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Double

Collaborators and Investigators

• Sponsor: National Center for Research Resources (NCRR)

Study record dates

Study Registration Dates

• First Submitted: June 1, 2000
• First Submitted That Met QC Criteria: June 1, 2000
• First Posted (Estimate): June 2, 2000

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: December 1, 2003

More Information

Terms related to this study

• Keywords: ALS
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: NCRR-M01RR00109-0750; M01RR000109 (U.S. NIH Grant/Contract)