The Experimental Treatment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis (ALS)
Study Purpose:The purpose of this study is to determine whether Nuedexta® improves speech, swallowing and saliva control in subjects with ALS
Disease:Amyotrophic Lateral Sclerosis (ALS), Familial ALS, Sporadic ALS
Study Type:Interventional Trial
Study Category:Drug Trial
Study Chair(s)/Principal Investigator(s):Merit Cudkowicz, MD, MSc (Massachusetts General Hospital)
Richard A. Smith, MD (Center for Neurologic Study, La Jolla, CA)
Clinicaltrials.gov ID (11 digit #):NCT01806857
Coordinating Center Contact InformationMassachusetts General Hospital
Boston, Massachusetts 02114 United States
Full Study Summary:Muscle weakness, the cardinal feature of ALS, leads to progressive loss of motor function affecting the limbs, tongue, respiratory and pharyngeal muscles. Symptomatic treatments such as the placement of a feeding tube can compensate for the inability to swallow. Riluzole, the only approved treatment for ALS, may slow disease progression but no treatment is curative and none have improved function. Since the effect of Nuedexta® on speech and swallowing has not been rigorously evaluated, a clinical trial has been designed to scientifically determine the effect of Nuedexta® on bulbar functions (speech, swallowing and salivation).
Approximately 60 eligible subjects with ALS will be recruited from multiple centers in the US. Subjects will be treated for 28 days (±3 days) with either Nuedexta® or placebo. A 10-15 day washout period will then occur. After the washout period, subjects will be crossed-over to the other treatment arm for an additional 28 days (± 3 days) of treatment. A follow-up telephone call will occur approximately 28 days after completion of the study.
Study Sponsor:ALS Association and Northeast ALS (NEALS) Consortium
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 Study Start Date:03/31/2013
Estimated Study Completion Date:11/02/2016
Posting Last Modified Date:04/30/2013
Date Study Added to alsconsortium.org:03/04/2013
- More Information
Time since Symptom Onset:N/A
Time since Diagnosis:N/A
Can participants use Riluzole?Yes
Study subjects meeting all of the following criteria will be allowed to enroll in the study:
1. ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
2. Age 18 years or older.
3. 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.
4. Capable of providing informed consent and following trial procedures.
5. Geographic accessibility to the site.
6. Women must not be able to become pregnant for the duration of the study and must be willing to be on two contraceptive therapies.
7. Slow vital capacity (SVC) measure ≥50% of predicted for gender, height, and age at the screening visit.
8. Must be able to swallow capsules throughout the course of the study, according to PI judgment.
9. 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 (riluzole-naÃ¯ve subjects are permitted in the study).
10. Subjects taking anti-sialorrhea medication(s) must be on a stable dose for at least 30 days prior to randomization (anti-sialorrhea naÃ¯ve subjects are permitted in the study)
11. Must be able to safely swallow at least 30cc of water for the water swallowing test
Study subjects meeting any of the following criteria during screening evaluations will be excluded from entry into the study:
1. Prior use of Nuedexta®.
2. Current use of dextromethorphan, quinidine, quinine, mefloquine or opioids.
3. History of quinidine, quinine, or mefloquine, or opiate-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions.
4. History of known sensitivity or intolerability to dextromethorphan.
5. Use of a monoamine oxidase inhibitor (MAOI) or within 14 days of stopping an MAOI.
6. Prolonged QT interval (QTc > 450 msec for women or >430 msec for men) , congenital long QT syndrome, history suggestive of torsades de pointes, or heart failure.
7. Complete atrioventricular (AV) block without implanted pacemaker, or subjects at high risk of complete AV block.
8. Concomitant use with drugs that both prolong QT interval and are metabolized by CYP2D6 (i.e., thioridazine or pimozide).
9. Exposure to any other experimental agent (off-label use or investigational) within 30 days prior to Baseline Visit.
10. Invasive ventilator dependence, such as tracheostomy.
11. Any history of either substance abuse within the past year, unstable psychiatric disease, cognitive impairment, or dementia, according to PI judgment.
12. Placement and usage of feeding tube.
13. Pregnant women or women currently breastfeeding
14. Unable to turn diaphragmatic pacing device off during swallowing tests
15. Salivatory Botox within 90 days (3 months) of screening
16. Salivatory radiation within 180 days (6 months) of screening
Site Contact Information
California Pacific Medical Center
San Francisco, California 94115
Saint Mary's Health Care
Grand Rapids, Michigan 49503
Hennepin County Medical Center
Minneapolis, Minnesota 55415
Lincoln, Nebraska 68506
Cleveland, Ohio 44195
Providence ALS Center
Portland, Oregon 97213
Washington D.C. 20007