Clinical Trial Nuedexta in Subjects With ALS

NCT ID: NCT01806857

Last Updated: 2017-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2015-03-31

Brief Summary

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).

Detailed Description

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.

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.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Nuedexta then Matching Placebo

Subjects in this arm will receive treatment with Nuedexta first for 28 days (±3 days) and then crossed over to receive treatment with matching placebo for 28 days (±3 days).

Group Type: OTHER

Nuedexta

Intervention Type: DRUG

Nuedexta PO (by mouth) for 28 ± 3 days

Matching Placebo

Intervention Type: DRUG

matching placebo PO (by mouth) for 28 ± 3 days

Matching Placebo then Nuedexta

Subjects in this arm will receive treatment with matching placebo first for 28 days (±3 days) and then crossed over to receive treatment with Nuedexta for 28 days (±3 days).

Group Type: OTHER

Nuedexta

Intervention Type: DRUG

Nuedexta PO (by mouth) for 28 ± 3 days

Matching Placebo

Intervention Type: DRUG

matching placebo PO (by mouth) for 28 ± 3 days

Interventions

Nuedexta

Nuedexta PO (by mouth) for 28 ± 3 days

Intervention Type: DRUG

Matching Placebo

matching placebo PO (by mouth) for 28 ± 3 days

Intervention Type: DRUG

Other Intervention Names

dextromethorphan hydrobromide and quinidine sulfate; sugar pill

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ALS Association

OTHER

Sponsor Role: collaborator

State University of New York - Upstate Medical University

OTHER

Sponsor Role: collaborator

Center for Neurologic Study, La Jolla, California,

OTHER

Sponsor Role: lead

Responsible Party

Richard A. Smith, MD

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard A Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Center for Neurologic Study (CNS)

Jeremy Shefner, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Barrow Neurological Institute

Merit E Cudkowicz, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital (MGH)

Locations

California Pacific Medical Center

San Francisco, California, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Saint Mary's Health Care

Grand Rapids, Michigan, United States

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Neurology Associates, P.C.

Lincoln, Nebraska, United States

The Cleveland Clinic

Cleveland, Ohio, United States

Providence ALS Center

Portland, Oregon, United States

Countries

United States

Related Links

http://www.alsconsortium.org/

Northeast ALS Consortium Website

http://www.alsa.org

ALS Association Website

Other Identifiers

3FKVAD

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2012P001274

Identifier Type: -

Identifier Source: org_study_id