A Phase 2 Pharmacodynamic Trial of Ezogabine on Neuronal Excitability in Amyotrophic Lateral Sclerosis
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
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
Coordinating Center Contact InformationMass General Hospital - Neurological Clinical Research Institute
165 Cambridge Street
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)
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
Gender:Neals Affiliated, Diseases, Study Type, Study Category, Study Status, Phase, Riluzole
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-naÃ¯ve 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
Fulton ALS Center
Phoenix, Arizona 85013
Beth Israel Deaconess Medical Center
435 Kirstein Building, Floor 4
Boston, Massachusetts 02215
Cedars-Sinai Medical Center
127 S. San Vincente Blvd.
Los Angeles, California 90048
Duke University Medical Center
932 Morrene Road
Durham, North Carolina 27705
Georgia Regents University
GRU Neuroscience Center
Augusta, Georgia 30912
Hospital for Special Surgery
525 East 71st Street
New York, New York 10021
Johns Hopkins Hospital
601 N. Carolina Street
Baltimore, Maryland 21287
Mass General Hospital
165 Cambridge Street
Boston, Massachusetts 02114
Mayo Clinic - Jacksonville
4500 San Pablo Road
Jacksonville, Florida 32224
University of California Irvine
200 S. Manchester Ave.
Orange County, California 92868
University of Michigan Medical Center
Ann Arbor, Michigan 48109