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 Status:

Closed

Phase:

Phase II

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

Neals Affiliated?

Yes

Coordinating Center Contact Information

Massachusetts General Hospital
Brenda Thornell / .(JavaScript must be enabled to view this email address) / 617-643-3102
.(JavaScript must be enabled to view this email address) 165 Cambridge Street
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 Enrollment:

60

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
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    N/A

    Min Vital Capacity (% predicted normal):

    50

    Time since Symptom Onset:

    N/A

    Time since Diagnosis:

    N/A

    Can participants use Riluzole?

    Yes


    Inclusion Criteria
    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-naïve 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 naïve subjects are permitted in the study)
    11. Must be able to safely swallow at least 30cc of water for the water swallowing test

    Exclusion Criteria
    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
    Marguerite Engel / Dallas Forshew, RN, BSN / .(JavaScript must be enabled to view this email address) / 415-600-3758 / 415-600-3928
    San Francisco, California 94115
    United States

    Saint Mary's Health Care
    Lynn Cherney / .(JavaScript must be enabled to view this email address) / 616-685-5091
    Grand Rapids, Michigan 49503
    United States

    Hennepin County Medical Center
    Cindy Rohde, RN / .(JavaScript must be enabled to view this email address) / 612-341-7923
    Minneapolis, Minnesota 55415
    United States

    Neurology Associates
    Becky Weber, RN / .(JavaScript must be enabled to view this email address) / 402-483-5517
    Lincoln, Nebraska 68506
    United States

    Cleveland Clinic
    Nicole Berry / .(JavaScript must be enabled to view this email address) / 216-445-1741
    Cleveland, Ohio 44195
    United States

    Providence ALS Center
    Chad Parks / .(JavaScript must be enabled to view this email address) / 503-216-2736
    Portland, Oregon 97213
    United States

    Georgetown University
    Connell "Rebecca" Owings, RN / .(JavaScript must be enabled to view this email address) / 202-444-2658
    Washington D.C. 20007
    United States