The purpose of this study is to evaluate the safety and effectiveness of creatine treatment
in amyotrophic lateral sclerosis (ALS). There is currently no known effective treatment for
ALS. It is known that nerve cells die in the brains and spinal cords of patients with ALS
but the cause of the cell death is unknown. It has been shown that there is overactive
nerve activity due to increased levels of a chemical called glutamate and that there is
abnormal cellular metabolism along with increased production of substance called "free
radicals." Improving cellular metabolism and readjusting the activity of glutamate in the
brain may be beneficial to ALS patients.
Creatine is a naturally occurring compound, which improves energy metabolism in cells.
Creatine has been given to patients with energy metabolism defects in their muscles, and to
athletes. Creatine improves survival in a mouse model of ALS. Three human subjects with
ALS have received creatine for up to six months without any side effects. Overall, creatine
has been well tolerated and safe.
Half of the subjects in this study will be selected by chance to receive creatine treatment
for 6 months and the other half to receive placebo. Neither the subject nor the investigator
will know which drug the subject is receiving, although this information will be available
in case of emergency. It is anticipated that all subjects will have the choice to receive
creatine after the 6 months study in an open-label study for an additional 12 months. A
total of 114 patients will participate at 15 centers. Approximately 8 subjects will be
enrolled at the Washington University.
The effectiveness of creatine will be determined first by assessing any changes in strength
in the arms and second by changes in grip strength, functional activities, electromyography
changes or changes of the level of SOH 2'dG in the urine.
- A clinical diagnosis of definite, probably or laboratory supported probably ALS,
either sporadic or familial ALS according to a modified El Escorial criteria
- Willing and able to give informed consent
- FVC greater than or equal to 50% predicted
- Evidence of abnormality in upper and/or lower extremity motor function (clinical
evidence of muscle atrophy and weakness in an upper and/or lower extremity). The
patient should have at least 4 or 8 testable upper extremity muscle groups.
- Subjects may take riluzole. Riluzole must have been at stable doses for at least
thirty days prior to baseline visit.
- If woman of childbearing age, must be non-lactating and surgically sterile or using
an effective method of birth control (double barrier or oral contraceptive) and have
a negative pregnancy test
- Disease duration less than five years