Rasagiline for amyotrophic lateral sclerosis: A randomized, controlled trial - PubMed (original) (raw)

Randomized Controlled Trial

. 2019 Feb;59(2):201-207.

doi: 10.1002/mus.26335. Epub 2018 Nov 26.

Dan Moore 2, Yunxia Wang 1, Maureen Walsh 1, Tahseen Mozaffar 3, Lauren Elman 4, Sharon P Nations 5, Hiroshi Mitsumoto 6, J Americo Fernandes 7, David Saperstein 8, Ghazala Hayat 9, Laura Herbelin 1, Chafic Karam 10, Jonathan Katz 2, Heather M Wilkins 1, Abdulbaki Agbas 11, Russell H Swerdlow 1, Regina M Santella 6, Mazen M Dimachkie 1, Richard J Barohn 1; Rasagiline Investigators of the Muscle Study Group and Western ALS Consortium

Collaborators, Affiliations

Randomized Controlled Trial

Rasagiline for amyotrophic lateral sclerosis: A randomized, controlled trial

Jeffrey M Statland et al. Muscle Nerve. 2019 Feb.

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.

Keywords: MAO-B inhibitor; amyotrophic lateral sclerosis; biomarker; controlled clinical trial; motor neuron disease; randomized; rasagiline.

© 2018 Wiley Periodicals, Inc.

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Conflict of interest statement

Disclosures: We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

All other authors no disclosures to report.

Figures

Figure 1.

Figure 1.. Study Flow Diagram.

One hundred-three were assessed for eligibility and 80 were randomized in a 3:1 ratio. Deaths were similar between groups. The placebo group was enriched with historical placebo controls from completed minocycline clinical trials.,

Figure 2.

Figure 2.. Survival curves and mitochondrial biomarkers.

A) There was no difference in survival between the rasagiline, placebo, and historical controls (Log-rank test Chi Squared=0.41, p=0.81). Vertical hash lines indicate withdrawals (dropouts). B) We found no treatment-related difference in the 6 months change in blood biomarkers (JC-1 above, ORAC below) which showed drug-target engagement in our prior study.

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