A Phase 2 Pharmacodynamic Trial of Ezogabine on Neuronal Excitability in Amyotrophic Lateral Sclerosis

Study Purpose:

The purpose of this study is to evaluate the safety and tolerability, dosing, and effect on neurophysiological excitability (motor neuron) measures of ezogabine in ALS subjects compared to non ALS subjects.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS, Healthy Volunteer

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Active, currently recruiting

Phase:

Phase II

Study Chair(s)/Principal Investigator(s):

Brian J. Wainger, M.D., PhD (MGH-NCRI)
Merit Cudkowicz, M.D. M. Sc. (MGH-NCRI)

Clinicaltrials.gov ID (11 digit #):

NCT02450552

Neals Affiliated?

Yes

Coordinating Center Contact Information

Mass General Hospital - Neurological Clinical Research Institute
Lindsay Pothier / .(JavaScript must be enabled to view this email address) / 617-643-5582
Armineuza Evora / .(JavaScript must be enabled to view this email address) / 617-724-5984
165 Cambridge Street
Suite 600
Boston, Massachusetts 02114 United States

Full Study Summary:

This research is being done in order to understand more about motor neurons in people who have amyotrophic lateral sclerosis (ALS or Lou Gehrig™s disease) compared to people without ALS. A motor neuron is a type of cell in the nervous system that can make muscles move. One of the major disease features of ALS is the progressive death of motor neurons. Past research has shown that the motor neurons of ALS patients may be producing more electrical activity than motor neurons of people without ALS, and that this extra electrical activity tires the neurons and contributes to their death. We are doing this research study to find out whether the drug ezogabine will lower motor neuron activity in people with ALS. We will also determine whether the drug is tolerable and safe for patients with ALS. Ezogabine has been approved by The Food and Drug Administration (FDA) for the treatment of patients with specific types of epilepsy. The FDA has not approved ezogabine to treat patients with ALS. At this time riluzole (Rilutek®) is the only drug approved by the FDA for the treatment of ALS. If you enroll in this trial you must not be taking riluzole, or must be taking a stable dose of riluzole for at least 30 days before the Baseline visit.

The study is funded by GlaxoSmithKline, the ALS Association, the Harvard Stem Cell Institute, and the Neurological Clinical Research Institute. This study is recruiting two types of participants:

1) healthy participants to undergo neurophysiological testing only
2) patients with Amyotrophic Lateral Sclerosis (ALS) to receive study drug and undergo several study procedures (repeated neurophysiological testing of the motor neurons in your brain and spine to see if the study drug has an effect on their excitability, repeated blood testing and optional lumbar puncture (to collect CSF) to evaluate drug levels and for other research purposes.

From this study, the researchers hope to learn more about ALS and its treatment.

Study Sponsor:

ALS Association (ALSA), GlaxoSmithKline (GSK), Harvard Stem Cell Institute (HSCI), Neurological Clinical Research Institute (NCRI)

Participant Duration:

ALS Subjects randomized to ten weeks treatment w/ one of the following 600mg/d ezogabine, 900 mg/d ezogabine, or placebo, 4 Neurophysiology visits over 14 weeks
Matched Health Control Group - Approximately 1 HC /site, 3 Neurophysiology visits over 12 weeks
Unmatched Healthy Controls- approximately 5 healthy controls/site 3(up to 5) Neurophysiology visits over 6 weeks or less, Study Clinical visits can be 3-4hours, phone visits about 20mins
Future contact highly preferred by all study subjects

Estimated Enrollment:

192 (120-ALS Subjects, 60 Health Controls, 12 Matched Health Controls)

Estimated Study Start Date:

04/30/2015

Estimated Study Completion Date:

11/30/2017

Posting Last Modified Date:

12/15/2016

Date Study Added to alsconsortium.org:

05/27/2015
  • Eligibility Criteria

    Gender:

    Neals Affiliated, Diseases, Study Type, Study Category, Study Status, Phase, Riluzole

    Minimum Age:

    18

    Maximum Age:

    80

    Min Vital Capacity (% predicted normal):

    50

    Time since Symptom Onset:

    N/A

    Time since Diagnosis:

    N/A

    Can participants use Riluzole?

    Yes


    1. Male or female, aged 18 to 80.
    2. Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
    3. Slow vital capacity (SVC) measure ≥ 50% of predicted for gender, height and age at the Screening Visit OR in the opinion of the SI, ability to perform and safely complete all study visit procedures.
    4. Subjects must not have taken riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days prior to the Screening Visit and continue on the stable dose throughout the course of the study (riluzole-naïve subjects are permitted in the study).
    5. Subjects must be able to swallow oral medication at the Screening Visit and expected to be able to swallow tablets throughout the course of the study.
    6. Capable of providing informed consent and following trial procedures.
    7. Geographically accessible to the site.
    8. Women must not be able to become pregnant (e.g., post menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and three months after study completion. Adequate contraception includes: abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception or other hormonal contraception, for example patch or contraceptive ring), intrauterine device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide, or another adequate method.
    9. Use of medications known to affect the neurophysiology measures in the study must be scheduled, not as needed (pro re nata, PRN). A subject must have been on a fixed dose for 30 days prior to the Screening Visit, and there must be no reason to believe that a subsequent change would be necessary during the course of the study. These medications include: benzodiazepines, muscle relaxants, tricyclic antidepressants, selective serotonin reuptake inhibitors, non-selective serotonin reuptake inhibitors, hypnotics (including anti-histamines) and anti-cholinergics.
    10. TMS shows sufficient MEP amplitude and/or NCS studies show sufficient CMAP amplitude (amplitudes defined in MOP).

  • Site Contact Information

    Barrow Neurological Institute
    Gale Kittle / .(JavaScript must be enabled to view this email address) / 602-406-4792
    Fulton ALS Center
    Phoenix, Arizona 85013
    United States

    Beth Israel Deaconess Medical Center
    Carmen Shin / .(JavaScript must be enabled to view this email address) / 617-667-4249
    435 Kirstein Building, Floor 4
    Boston, Massachusetts 02215
    United States

    Cedars-Sinai Medical Center
    Ashley Fetterman / .(JavaScript must be enabled to view this email address) / 310-423-6580
    Vy Nguyen / .(JavaScript must be enabled to view this email address) / 424-315-2361
    127 S. San Vincente Blvd.
    Los Angeles, California 90048
    United States

    Duke University Medical Center
    Karen Grace / .(JavaScript must be enabled to view this email address) / 919-668-2844
    932 Morrene Road
    Durham, North Carolina 27705
    United States

    Georgia Regents University
    Brandy Quarles / .(JavaScript must be enabled to view this email address) / 706-721-2681
    Nicole Smalley / .(JavaScript must be enabled to view this email address) / 706-721-2681
    GRU Neuroscience Center
    Augusta, Georgia 30912
    United States

    Hospital for Special Surgery
    Shara Holzberg / .(JavaScript must be enabled to view this email address) / 212-774-2361
    Mona Shahbazi / .(JavaScript must be enabled to view this email address) / 646-797-8657
    525 East 71st Street
    New York, New York 10021
    United States

    Johns Hopkins Hospital
    Kristen Riley / .(JavaScript must be enabled to view this email address) / 410-955-8511
    Alpa Uchil / .(JavaScript must be enabled to view this email address) / 410-955-8511
    601 N. Carolina Street
    Baltimore, Maryland 21287
    United States

    Mass General Hospital
    Mehdi Husain / .(JavaScript must be enabled to view this email address) / 617-643-2499
    165 Cambridge Street
    Boston, Massachusetts 02114
    United States

    Mayo Clinic - Jacksonville
    Amelia Robertson / .(JavaScript must be enabled to view this email address) / 904-953-9498
    Pam Desaro / .(JavaScript must be enabled to view this email address) / 904-953-7720
    4500 San Pablo Road
    Jacksonville, Florida 32224
    United States

    University of California Irvine
    Veena Mathew / .(JavaScript must be enabled to view this email address) / 714-456-2864
    Veronica Martin / .(JavaScript must be enabled to view this email address) / 714-456-7760
    200 S. Manchester Ave.
    Orange County, California 92868
    United States

    University of Michigan Medical Center
    Jayna Duell / .(JavaScript must be enabled to view this email address) / 734-763-9037
    Blake Swihart / .(JavaScript must be enabled to view this email address) / 734-763-7275
    4019 AAT-BSRB
    Ann Arbor, Michigan 48109
    United States