title: Enhanced Bulbar Function in Amyotrophic Lateral Sclerosis: The Nuedexta Treatment Trial.
abstract: The goal of this randomized, blinded, crossover clinical trial was to determine whether Nuedexta (dextromethorphan and quinidine) enhanced speech, swallowing, and salivation in patients with ALS. Sixty patients with amyotrophic lateral sclerosis (ALS) received either Nuedexta or placebo for 28 to 30 days, followed by a 10 to 15-day washout period. Subsequently, patients were switched to the opposite treatment arm for the remaining days of the trial. The primary endpoint was a reduction in the self-report Center for Neurologic Study Bulbar Function Scale (CNS-BFS) score. The rater-administered ALS Functional Rating Scale Revised was the principal secondary endpoint. The CNS-BFS score improved with active treatment, decreasing from a mean of 59.3 in the placebo arm of the trial to 53.5 during the drug-treatment arm (p < 0.001). Each of the individual domains of bulbar function interrogated by the CNS-BFS responded to treatment with Nuedexta as follows: salivation: 15.8 versus 14.3 (p = 0.004); speech: 24.6 versus 22.2 (p = 0.003); swallowing: 18.9 versus 17.1 (p = 0.009). Similarly, the bulbar component of the ALS Functional Rating Scale Revised improved with active treatment (p = 0.003), although the drug did not affect the motor and respiratory components of this scale. This study is unique for several reasons. Firstly, it was driven by patient reports of improved speech and swallowing while taking Nuedexta for control of emotional lability. Secondly, the study was conducted over a short duration (70 days), and thirdly, a self-report scale was selected as the principle outcome measure. Considering the importance of bulbar functions, these results, if confirmed, point to an additional use of Nuedexta as an adjunct to the management of ALS.
authors.affiliation: Center for Neurologic Study, 7590 Fay Ave., Suite 517, La Jolla, CA, 92037, USA. cnsonline@ymail.com.
authors.forename: Richard
authors.identifier: http://orcid.org/0000-0003-4200-9268
authors.initials: R
authors.lastname: Smith
authors.affiliation: Cleveland Clinic, Department of Neurology, Mail Code S90, 9500 Euclid Ave., Cleveland, OH, 44195, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Pioro
authors.affiliation: Center for Neurologic Study, 7590 Fay Ave., Suite 517, La Jolla, CA, 92037, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Myers
authors.affiliation: Georgetown University Hospital, Department of Neurology, Pasquerilla Healthcare Center, 7th Floor, 3800 Reservoir Road, N.W., Washington, DC, 20007, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Sirdofsky
authors.affiliation: Providence ALS Center, 5050 NE Hoyt St., #315, Portland, OR, 97123, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Goslin
authors.affiliation: Department of Neurology, University of Minnesota, 420 Delaware St. SE, Minneapolis, MN, 55455, USA.
authors.forename: Gregg
authors.initials: G
authors.lastname: Meekins
authors.affiliation: Neurological Clinical Research Institute and Biostatistics Center, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.|Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Neurology, University of Florida College of Medicine, HSC P.O. Box 100236, Gainesville, FL, 32610-0236, USA.
authors.forename: James
authors.initials: J
authors.lastname: Wymer
authors.affiliation: Neurological Clinical Research Institute and Biostatistics Center, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.|Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
authors.forename: Merit
authors.initials: M
authors.lastname: Cudkowicz
authors.affiliation: Neurological Clinical Research Institute and Biostatistics Center, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.|Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Macklin
authors.affiliation: Neurological Clinical Research Institute and Biostatistics Center, Massachusetts General Hospital, 15 Parkman Street, Boston, MA, 02114, USA.|Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
authors.forename: David
authors.initials: D
authors.lastname: Schoenfeld
authors.affiliation: Neurology Associates, 2631 S. 70th St., Lincoln, NE, 68506, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Pattee
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D018592:Cross-Over Studies; D003915:Dextromethorphan / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011802:Quinidine / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; C507057:dextromethorphan - quinidine combination; D003915:Dextromethorphan; D011802:Quinidine
keywords: Amyotrophic lateral sclerosis; Nuedexta; bulbar function; clinical trial; dextromethorphan; self-report scale