The purpose of this study is to determine whether nine months of administation of creatine monohydrate results in an increase in muscle strength in patients with amyotrophic lateral sclerosis (ALS).

Condition	Treatment or Intervention	Phase
Amyotrophic Lateral Sclerosis (ALS)	Drug: Creatine Monohydrate	Phase III

Further Study Details: 

Expected Total Enrollment:  156

Introduction: 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.

Ages Eligible for Study:  21 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

• A clinical diagnosis of probable or definite lab-supported ALS, either SALS or FALS, according to modified El Escorial criteria.
• Males or females, 21 to 80 years of age.
• Patients receiving treatment with Rilutek® (riluzole) must be on a stable dose for at least 30 days immediately prior to enrollment.
• Women of childbearing potential must be non-lactating and surgically sterile or using an effective method of birth control (double barrier or oral contraception) and have a negative pregnancy test. Women will be considered menopausal if they have not had a menstrual cycle (period) for two years.
• Disease duration less than five years since symptom onset.
• At least 5 of 10 testable upper extremity muscle groups of MRC grade 4 or better.
• The patient must have given informed consent that has been approved by the appropriate Institutional Review Board (IRB).

Jeffrey Rosenfeld, MD, PhD      704.446.6256    jeffrey.rosenfeld@carolinashealthcare.org
Ruth King, RN      704.355-8699    ruth.king@carolinashealthcare.org

California
      University of California, San Francisco, San Francisco,  California,  94115,  United States; Recruiting
Illinois
      Rush-Presbyterian St. Luke's Medical Center, Chicago,  Illinois,  60612,  United States; Recruiting
Kansas
      University of Kansas, Kansas City,  Kansas,  66160,  United States; Recruiting
New Mexico
      University of New Mexico, Albuquerque,  New Mexico,  87131,  United States; Recruiting
North Carolina
      Carolinas Medical Center, Charlotte,  North Carolina,  28203-5812,  United States; Recruiting
      Duke University Medical Center, Durham,  North Carolina,  27705,  United States; Not yet recruiting
Texas
      University of Texas Health Science Center, San Antonio,  Texas,  48284-7883,  United States; Recruiting
Virginia
      University of Virginia Health System, Charlottesville,  Virginia,  22908,  United States; Recruiting

Study ID Numbers:  AGI-ALS-III-01; Orphan Drug:01-1527
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  September 17, 2003
ClinicalTrials.gov Identifier:  NCT00069186
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08