Rasagiline for amyotrophic lateral sclerosis: A randomized, controlled trial

The Rasagiline Investigators of the Muscle Study Group and Western ALS Consortium

doi:10.1002/mus.26335

Rasagiline for amyotrophic lateral sclerosis: A randomized, controlled trial

The Rasagiline Investigators of the Muscle Study Group and Western ALS Consortium

Mailman School of Public Health

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34 Citations (Scopus)

Résumé

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.

Langue d'origine	English
Pages (de-à)	201-207
Nombre de pages	7
Journal	Muscle and Nerve
Volume	59
Numéro de publication	2
DOI	https://doi.org/10.1002/mus.26335
Statut de publication	Published - févr. 2019

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Abbreviations: ALS, amyotrophic lateral sclerosis; ALSFRS-R, ALS Functional Rating Scale—Revised; ALSQOL, ALS Quality of Life; ELISA, enzyme-linked immunosorbent assay; FTD, frontotemporal dementia; FVC, forced vital capacity; IsoP, isoprostane; LME, linear mixed effects; MAO-B, monoamine oxidase B; ORAC, oxygen radical antioxidant capacity; PRO-ACT, Pooled Resource Open-Access ALS Clinical Trials; RCT, randomized, controlled trial; SVC, slow vital capacity; TDP-43, TAR DNA-binding protein 43; WALS, Western ALS Study Group Key words: amyotrophic lateral sclerosis, biomarker, MAO-B inhibitor, motor neuron disease, randomized, controlled clinical trial, rasagiline Funding: U.S. Food and Drug Administration Orphan Products Division (RO1 FD003739 to H.M.W., R.H.S., and R.J.B.; P30 AG035982 to H.M.W. and R.H.S.); NCATS grant awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research (CTSA grants UL1TR000001 and KL2TR000119 to J.M.S.); Columbia’s Biomarkers Laboratory was supported by grant ES009089.

Bailleurs de fonds	Numéro du bailleur de fonds
ELISA	TDP-43
U.S. Food and Drug Administration	RO1 FD003739, P30 AG035982
National Institute on Aging	P30AG035982
National Center for Advancing Translational Sciences	UL1TR000001, KL2TR000119, ES009089

ASJC Scopus Subject Areas

Physiology
Clinical Neurology
Cellular and Molecular Neuroscience
Physiology (medical)

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10.1002/mus.26335

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title = "Rasagiline for amyotrophic lateral sclerosis: A randomized, controlled trial",

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.",

author = "{The Rasagiline Investigators of the Muscle Study Group and Western ALS Consortium} and Statland, {Jeffrey M.} and Dan Moore and Yunxia Wang and Maureen Walsh and Tahseen Mozaffar and Lauren Elman and Nations, {Sharon P.} and Hiroshi Mitsumoto and Fernandes, {J. Americo} and David Saperstein and Ghazala Hayat and Laura Herbelin and Chafic Karam and Jonathan Katz and Wilkins, {Heather M.} and Abdulbaki Agbas and Swerdlow, {Russell H.} and Santella, {Regina M.} and Dimachkie, {Mazen M.} and Barohn, {Richard J.} and Russell Swerdlow and Yunxia Wang and Jeffrey Statland and Dimachkie, {Mazen M.} and Melanie Glenn and Mamatha Pasnoor and Maureen Walsh and Kelley Emmons and Kathryn Johns and Yolanda Harness and Laura Herbelin and Jonathan Katz and Miller, {Robert G.} and Dallas Forshew and Marguerite Engel and Namita Goyal and Tiyonnoh Cash and Veena Mathew and Veronica Martin and David Saperstein and Todd Levine and Lynn Flynne and Chafic Karam and Diana Dimtrov and Lauren Elman and Leo McCluskey and Kelly Almasy and Mary Kelley and Fernandes, {J. Americo M.} and Regina Santella",

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AU - The Rasagiline Investigators of the Muscle Study Group and Western ALS Consortium

AU - Statland, Jeffrey M.

AU - Moore, Dan

AU - Wang, Yunxia

AU - Walsh, Maureen

AU - Mozaffar, Tahseen

AU - Elman, Lauren

AU - Nations, Sharon P.

AU - Mitsumoto, Hiroshi

AU - Fernandes, J. Americo

AU - Saperstein, David

AU - Hayat, Ghazala

AU - Herbelin, Laura

AU - Karam, Chafic

AU - Katz, Jonathan

AU - Wilkins, Heather M.

AU - Agbas, Abdulbaki

AU - Swerdlow, Russell H.

AU - Santella, Regina M.

AU - Dimachkie, Mazen M.

AU - Barohn, Richard J.

AU - Swerdlow, Russell

AU - Wang, Yunxia

AU - Statland, Jeffrey

AU - Dimachkie, Mazen M.

AU - Glenn, Melanie

AU - Pasnoor, Mamatha

AU - Walsh, Maureen

AU - Emmons, Kelley

AU - Johns, Kathryn

AU - Harness, Yolanda

AU - Herbelin, Laura

AU - Katz, Jonathan

AU - Miller, Robert G.

AU - Forshew, Dallas

AU - Engel, Marguerite

AU - Goyal, Namita

AU - Cash, Tiyonnoh

AU - Mathew, Veena

AU - Martin, Veronica

AU - Saperstein, David

AU - Levine, Todd

AU - Flynne, Lynn

AU - Karam, Chafic

AU - Dimtrov, Diana

AU - Elman, Lauren

AU - McCluskey, Leo

AU - Almasy, Kelly

AU - Kelley, Mary

AU - Fernandes, J. Americo M.

AU - Santella, Regina

PY - 2019/2

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N2 - 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.

AB - 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.

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Rasagiline for amyotrophic lateral sclerosis: A randomized, controlled trial

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