Trial of Indinavir Does Not Demonstrate Benefit for People with ALS
May 4, 2004
On April 27 at the annual meeting of the American Academy of Neurology in San Francisco, Calif., Stephen N. Scelsa, M.D. presented results from a pilot trial of the anti-retroviral drug indinavir in patients with ALS. The study was designed to determine the safety and efficacy of indinavir in slowing disease progression.
Funding for this study was provided by ZazAngels (a group formed by the friends of Emmy award-winning actor Michael Zaslow) and the Adele Zinberg, M.D. ALS Research Fund through The ALS Association's Greater New York Chapter.
"Based on the clinical practice observations, it was very important to conduct this study. This is not yet a published peer-reviewed study, and further review will determine if additional evaluation of indinavir or other anti-retroviral drugs is indicated," said Mary Lyon, ALSA's vice president of patient services.
Results: The study compared physical function, as measured by the ALS Functional Rating Scale, between people who received indinavir and those who received a placebo. This study found that there was no significant difference in function between the two groups. Measures of general muscle and breathing muscle strength, the forced vital capacity (FVC), were also compared between the two groups of patients. There was no statistically significant difference in the general muscle strength or in the FVC between the groups; although, there was a trend toward a slower rate of decline in the FVC with the people in the placebo group. Forty-six patients were enrolled in this study and 21 completed the trial.
Side effects were observed, including kidney stones that occurred in 4 (17%) indinavir-treated patients; in all of these, patients were unable to maintain the required water intake. Eight patients had gastrointestinal side effects; of these, seven patients were treated with indinavir, representing 30% of those treated with indinavir.
"Although we recommend against this particular anti-retroviral drug for people with ALS, the door is still open for further study of other treatments in this class of drugs," commented Dr. Scelsa. Scelsa reported the results during a platform presentation of the double blind, placebo-controlled trial.
In the discussion period after the presentation, questions were raised about whether the study was designed to be able to determine if indinavir showed efficacy in ALS. Issues of small sample size were noted.
Background: Studies have raised the possibility of retroviral infection in ALS. A reversible ALS-like syndrome occurs rarely in patients with HIV, who are treated with anti-retroviral drugs. Indinavir is an anti-retroviral drug. Indinavir is in a group of drugs, protease inhibitors that interfere with the pre-programmed death of white blood cells, by a mechanism that may be relevant to motor neuron cell death in ALS. It is unclear if retroviral infection is important in ALS. Dr. Scelsa is the medical director of the Beth Israel certified ALSA CenterSM in New York City. Merck Pharmaceuticals donated the drug used in this study.
