Jeffrey M Statland1, Dan Moore2, Yunxia Wang1, Maureen Walsh1, Tahseen Mozaffar3, Lauren Elman4, Sharon P Nations5, Hiroshi Mitsumoto6, J Americo Fernandes7, David Saperstein8, Ghazala Hayat9, Laura Herbelin1, Chafic Karam10, Jonathan Katz2, Heather M Wilkins1, Abdulbaki Agbas11, Russell H Swerdlow1, Regina M Santella6, Mazen M Dimachkie1, Richard J Barohn1. 1. Department of Neurology, University of Kansas Medical Center, 3901 Rainbow Boulevard, MS 2012, Kansas City, Kansas, 66160, USA. 2. The Forbes Norris MDA/ALS Research Center, California Pacific Medical Center, San Francisco, California, USA. 3. Department of Neurology, University of California, Irvine, Irvine, California, USA. 4. Department of Neurology, University of Pennsylvania, Philadelphia, Pennslyvania, USA. 5. Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6. Department of Neurology, Columbia University, New York, New York, USA. 7. Department of Neurology, University of Nebraska Medical Center, Omaha, Nebraska, USA. 8. Phoenix Neurological Associates, Phoenix, Arizona, USA. 9. Department of Neurology, St. Louis University, St. Louis, Missouri, USA. 10. Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA. 11. Department of Biosciences, Kansas City University of Medicine and Bioscience, Kansas City, Missouri, USA.
Abstract
INTRODUCTION:Rasagiline is a monoamine oxidase B (MAO-B) inhibitor with possible neuroprotective effects in patients with amyotrophic lateral sclerosis (ALS). METHODS: We performed a randomized, double-blind, placebo-controlled trial of 80 ALS participants with enrichment of the placebo group with historical controls (n = 177) at 10 centers in the United States. Participants were randomized in a 3:1 ratio to 2 mg/day rasagiline or placebo. The primary outcome was average slope of decline on the ALS Functional Rating Scale-Revised (ALSFRS-R). Secondary measures included slow vital capacity, survival, mitochondrial and molecular biomarkers, and adverse-event reporting. RESULTS: There was no difference in the average 12-month ALSFRS-R slope between rasagiline and the mixed placebo and historical control cohorts. Rasagiline did not show signs of drug-target engagement in urine and blood biomarkers. Rasagiline was well tolerated with no serious adverse events. DISCUSSION: Rasagiline did not alter disease progression compared with controls over 12 months of treatment. Muscle Nerve 59:201-207, 2019.
RCT Entities:
INTRODUCTION:Rasagiline is a monoamine oxidase B (MAO-B) inhibitor with possible neuroprotective effects in patients with amyotrophic lateral sclerosis (ALS). METHODS: We performed a randomized, double-blind, placebo-controlled trial of 80 ALSparticipants with enrichment of the placebo group with historical controls (n = 177) at 10 centers in the United States. Participants were randomized in a 3:1 ratio to 2 mg/day rasagiline or placebo. The primary outcome was average slope of decline on the ALS Functional Rating Scale-Revised (ALSFRS-R). Secondary measures included slow vital capacity, survival, mitochondrial and molecular biomarkers, and adverse-event reporting. RESULTS: There was no difference in the average 12-month ALSFRS-R slope between rasagiline and the mixed placebo and historical control cohorts. Rasagiline did not show signs of drug-target engagement in urine and blood biomarkers. Rasagiline was well tolerated with no serious adverse events. DISCUSSION: Rasagiline did not alter disease progression compared with controls over 12 months of treatment. Muscle Nerve 59:201-207, 2019.
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