Study Purpose:
The purpose of this study is to determine whether Nuedexta is effective in the treatment of symptoms (impaired speech, swallowing, and saliva control)associated with Amyotrophic Lateral Sclerosis (ALS).Study Status:
Not recruiting
Disease:
Amyotrophic Lateral Sclerosis (ALS)
Study Type:
Interventional
Type of Intervention:
Drug
Intervention Name:
Nuedexta, Matching Placebo
Placebo:
Phase:
Phase 2
Study Chair(s)/Principal Investigator(s):
Richard A Smith, MD, Center for Neurologic Study (CNS), Jeremy Shefner, MD, PhD, Barrow Neurological Institute, Merit E Cudkowicz, MD, MSc, Massachusetts General Hospital (MGH)
Clinicaltrials.gov ID:
Neals Affiliated?
Yes
Coordinating Center Contact Information
Massachusetts General Hospital
165 Cambridge Street
Boston, Massachusetts, 02114 United States
Full Study Summary:
Unexpectedly, Nuedexta®, approved for the treatment of labile emotionality that occurs in association with ALS and other neurological disorders, has been observed to improve bulbar function, primarily speech and swallowing, in a number of neurological disorders, including ALS. The basis for this is conjectural but likely due to a direct effect of the drug on motor neurons in the part of the brain that controls speech and swallowing. The same part of the brain appears to modulate the expression of emotions and interestingly the site of action of the drug is the same as a site that has been implicated in a juvenile form of ALS.
This is a multicenter, randomized double-blind, placebo controlled, cross over study evaluating the palliative effect of Nuedexta® on bulbar dysfunction. It is expected that approximately 60 ALS patients from 7 clinical centers in the US will be enrolled.
Study Sponsor:
Center for Neurologic Study, La Jolla, California,
Participant Duration:
Subjects will take study treatment for approximately 2 months. Subjects will have 5 in-person visits and 1 telephone visit during the study.
Estimated Enrollment:
90
Estimated Study Start Date:
03 / 31 / 2013
Estimated Study Completion Date:
03 / 01 / 2015
Posting Last Modified Date:
03 / 24 / 2017
Date Study Added to neals.org:
03 / 07 / 2013
Minimum Age:
18 Years
Maximum Age:
N/A
Can participants use Riluzole?
Yes
Inclusion Criteria:- ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria
- Age 18 years or older
- Exhibits bulbar dysfunction manifested by dysarthria and/or dysphagia, according to PI judgment, exhibits a score of 55 or above on the CNS-Bulbar Function Scale
- Capable of providing informed consent and following trial procedures
- Geographic accessibility to the site
- Women must not be able to become pregnant for the duration of the study and must be willing to be on two contraceptive therapies
- Slow vital capacity (SVC) measure ≥50% of predicted for gender, height, and age at the screening visit
- Must be able to swallow capsules throughout the course of the study, according to PI judgment
- Subjects must not have taken riluzole for at least 30 days or be on a 50mg BID dose of riluzole for at least 30 days prior to randomization (subjects how have never taken riluzole are permitted in the study)
- Subjects taking anti-sialorrhea medication(s) must be on a stable dose for at least 30 days prior to randomization (anti-sialorrhea naïve subjects are permitted in the study)
- Must be able to safely swallow at least 30 milliliters (mLs) of water for the water swallowing test
Exclusion Criteria:
- Prior use of Nuedexta®
- Current use of dextromethorphan, quinidine, quinine, mefloquine or opioids
- History of quinidine, quinine, or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions
- History of known sensitivity or intolerability to dextromethorphan
- Use of an mono amine oxidase inhibitor (MAOI) or within 14 days of stopping an MAOI
- Prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de pointes, or heart failure
- Complete atrioventricular (AV) block without implanted pacemaker, or subjects at high risk of complete AV block
- Concomitant use with drugs that both prolong QT interval and are metabolized by cytochrome P 2D6 (CYP2D6) (i.e., thioridazine or pimozide)
- Exposure to any other experimental agent (off-label use or investigational) within 30 days prior to Baseline Visit
- Invasive ventilator dependence, such as tracheostomy
- Any history of either substance abuse within the past year, unstable psychiatric disease, cognitive impairment, or dementia, according to PI judgment
- Placement and/or usage of feeding tube
- Pregnant women or women currently breastfeeding
- Unable to turn diaphragm pacing device off during swallowing tests
- Salivatory Botox within 90 days (3 months) of screening
- Salivatory radiation within 180 days (6 months) of screening
California Pacific Medical Center
San Francisco, California
94115
United States
Georgetown University Medical Center
Washington D.C., District of Columbia
20007
United States
Saint Mary's Health Care
Grand Rapids, Michigan
49503
United States
Hennepin County Medical Center
Minneapolis, Minnesota
55415
United States
Neurology Associates, P.C.
Lincoln, Nebraska
68506
United States
The Cleveland Clinic
Cleveland, Ohio
44195
United States
Providence ALS Center
Portland, Oregon
97213
United States