A Multicenter, Double-Blind, Placebo-Controlled, Study to Investigate the Safety and Efficacy of Lithium in Combination With Riluzole in Volunteers With Amyotrophic Lateral Sclerosis (ALS)

Study Purpose:

The purpose of this study is to compare the effectiveness of lithium combined with riluzole to riluzole combined with placebo in people with amyotrophic lateral sclerosis.

Disease:

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

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Not enrolling

Phase:

Phase III

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

Merit Cudkowicz, MD, MSc (Massachusetts General Hospital, Boston, MA)
Swati Aggarwal, MD (Massachusetts General Hospital, Boston, MA)
Lorne Zinman, MD, MSc, FRCPC (Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto, CA)
Jinsy Andrews, MD (Columbia University, New York, NY)

Clinicaltrials.gov ID (11 digit #):

NCT00818389

Neals Affiliated?

Yes

Coordinating Center Contact Information

Massachusetts General Hospital
.(JavaScript must be enabled to view this email address)
.(JavaScript must be enabled to view this email address) Massachusetts United States

Full Study Summary:

Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative disorder that results in progressive wasting and paralysis of voluntary muscles.

In this double blind, randomized, placebo-controlled clinical trial, researchers will evaluate the safety and effectiveness of the drug lithium given in combination with riluzole, a drug commonly used to treat ALS, compared to a placebo given in combination with riluzole.

Approximately 250 participants will be recruited from multiple centers, in the US and Canada, that belong to the Northeast ALS Consortium (NEALS) and the Canadian ALS Clinical Trials and Research Network (CALS). Enrollment will occur in stages. Initially 84 participants will be enrolled in the trial. An interim analysis using available data will occur after the 84th participant is enrolled. During this time, the Data and Safety Monitoring Board (DSMB) appointed by the National Institutes of Health (NIH) may decide to stop the trial for efficacy or futility reasons or to stop enrollment and request that follow-up continue with the 84 participants already enrolled in the trial, or the DSMB may decide to continue enrollment.

Participants will be randomized to one of two arms of the study. Arm one will receive lithium and riluzole. Arm two will receive riluzole and placebo (an inactive substance). All participants will be receiving riluzole. After screening and randomization, participants will be followed every 4 weeks for the first 12 weeks. Subsequent in-person visits will occur every 8 weeks with a final visit at week 52. Between in-person visits, telephone interviews will take place every 4 weeks to administer the Amyotropic Lateral Sclerosis Functional Rating Scale—Revised (ALSFRS-R) questionnaire. A follow-up telephone interview will occur at week 56 (off study medication) to review adverse events. The primary outcome measure is disease progression as measured by the ALSFRS-R questionnaire. Participants randomized to placebo whose disease progresses will be crossed over to lithium for the remaining period of the study (up to 52 weeks total).

Duration of the study for participants is 56 weeks which includes 52 weeks of treatment and a followup telephone interview at week 56.

Study Sponsor:

ALS Association; ALS Society of Canada

Participant Duration:

56 weeks

Estimated Enrollment:

84

Estimated Study Start Date:

11/02/2016

Estimated Study Completion Date:

11/02/2016

Posting Last Modified Date:

10/31/2011

Date Study Added to alsconsortium.org:

11/03/2011
  • More Information
    This study has been terminated.
    (NINDS DSMB recommended trial be terminated for futility after reviewing an interim analysis of 84 subjects.)
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    N/A

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?


    Inclusion Criteria:

    •Familial or sporadic ALS
    •Participants diagnosed with laboratory supported probable, clinically possible, probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria
    •Disease duration from symptom onset no greater than 36 months at the Screening Visit
    •Age 18 years or older
    •Capable of providing informed consent and complying with trial procedures
    •On a stable dose of riluzole 50 milligrams (mg) twice per day(bid) for at least 30 days prior to screening
    •Vital capacity (VC) equal to or more than 60% predicted normal value for gender, height and age at the Screening Visit
    •Creatinine <1.5 milligrams per deciliter (mg/dl) [133 micromoles per liter (umol/L]
    •Participants maintained on thyroid medication must be euthyroid for at least 3 months before the Screening Visit.
    •Participants with psoriasis must have inactive disease for at least 30 days before the Screening Visit.
    •Women must not be able to become pregnant (e.g., post menopausal for at least one year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Women of childbearing potential must have a negative serum pregnancy test at the Screening Visit and be non-lactating.
    •Geographic accessibility to the study site
    Exclusion Criteria:

    •History of known sensitivity or intolerability to lithium or to any other related compound
    •Prior exposure to lithium within 90 days of the Screening Visit
    •Exposure to any investigational agent within 30 days of the Screening Visit
    •Participants who are malnourished, dehydrated or on a sodium-free diet will be excluded due to the potential side effects of lithium carbonate
    •Use of digoxin or iodide salts [e.g. calcium iodide, hydrogen iodide (hydriodic acid), iodide, iodinated glycerol (Organidin), iodine, potassium iodide (SSKI), and sodium iodide supplementation beyond table salt]
    •Presence of any of the following clinical conditions: Substance abuse within the past year; Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease; autoimmune deficiency syndrome (AIDS) or AIDS-related complex; Clinically active psoriasis within 30 days of the Screening Visit; Unstable psychiatric illness defined as psychosis (hallucinations or delusions) or untreated major depression within 90 days of the Screening Visit; Screening serum creatinine greater than or equal to 1.5 mg/dL (133 umol/L), thyroid stimulating hormone (TSH) > 20% above the upper limit; Presence of any clinically significant conduction abnormalities on electrocardiogram (ECG); or Lactating or have a positive serum pregnancy test at the Screening Visit.

  • Site Contact Information

    Phoenix Neurological Assoc.
    1331 N. 7th Street, Suite 350
    Phoenix, Arizona 85006
    United States

    Cedars-Sinai ALS Center, Neurology Specialty Clinic
    8730 Alden Drive, Thalians, E 245
    Los Angeles, California 90048
    United States

    UCSF ALS Center, University of California San Francisco, Neurology
    Box 0114, UCSF
    San Francisco, California 94143
    United States

    University of Miami, Miller School of Medicine
    150 NW 14th Street, Suite 609
    Miami, Florida 33136
    United States

    Mayo Clinic-Jacksonville, Neurology Department
    4500 San Pablo Road
    Jacksonville, Florida 32224
    United States

    ndiana University, Department of Neurology
    1050 Wishard Blvd, RG 6
    Indianapolis, Indiana 46202
    United States

    University of Kentucky Medical Center, BAMC, Department of Neurology
    Room A307, 1101 Veteran's Drive
    Lexington, Kentucky 40502
    United States

    Johns Hopkins University, Department of Neurology
    600 N. Wolfe St, Meyer 6-181
    Baltimore, Maryland 21287
    United States

    Massachusetts General Hospital
    149 13th St, Room 2266
    Charlestown, Massachusetts 02129
    United States

    Wayne State University, Department of Neurology
    4201 St. Antoine, 8C UHC
    Detroit, Michigan 48201
    United States

    Hennepin County Medical Center, Dept of Neurology
    701 Part Ave S, P5-200
    Minneapolis, Minnesota 55415
    United States

    Washington University
    660 S. Euclid Ave., Box 8111 Neurology
    St. Louis, Missouri 63110
    United States

    SUNY Upstate Medical University
    750 E Adams St, 6610UH
    Syracuse, New York 13210
    United States

    Columbia Univ Med Ctr, Eleanor and Lou Gehrig ALS/MDA Center
    710 West 168th St, 9th Floor
    New York, New York 10032
    United States

    Duke University Medical Center
    Box 3333
    Durham, North Carolina 27707
    United States

    Wake Forest University, ALS Center
    Paul Sticht Center, Ground Floor, Medical Center Blvd
    Winston-Salem, North Carolina 27157-1078
    United States

    Ohio State University, Neuromuscular Division
    1654 Uphan Drive, 417 Means Hall
    Columbus, Ohio 43210
    United States

    Drexel University College of Medicine
    245 North 15th Street
    Philadelphia, Pennsylvania 19103
    United States

    Penn State Hershey Medical Center, Department of Neurology
    Hershey, Pennsylvania 17033
    United States

    Texas Neurology, PA
    6301 Gaston Ave, Suite 400 West Tower
    Dallas, Texas 75214
    United States

    University of Vermont, Department of Neurology
    89 Beaumont Drive, Given Bldg, Room C-225
    Burlington, Vermont 05405
    United States

    University of Virginia, Department of Neurology
    3100 Hospital Drive
    Charlottesville, Virginia 22908
    United States

    University of Calgary, Area 3, University of Calgary Medical Clinic
    3350 Hospital Drive NW Foothills Hosp. Grounds
    Calgary, Alberta T2N 4N1
    Canada

    University of Alberta, Division of Neurology, Dept of Medicine
    2E3.17 Walter C. MacKenzie Health Sciences Center
    Edmonton, Alberta T6G 2B7
    Canada

    University of Manitoba
    Winnipeg, R3T 2N2
    Canada

    University of British Columbia
    GF Strong Rehab Centre, 4255 Laurel Street
    Vancouver, British Columbia V5Z 2G9
    Canada

    McMaster University, McMaster University Medical Centre
    Hamilton Health Sciences, 1200 Main Street West, Room 4U7, Box 2000
    Hamilton, Ontario L8N 3Z5
    Canada

    Dalhousie University, Capital District Health Authority
    Queen Elizabeth II Health Sciences Centre, P.O. Box 9000, Summer Street
    Halifax, Nova Scotia B3K 6A5
    Canada

    University of New Brunswick
    The Stan Cassidy Centre for Rehabilitation
    Fredericton, New Brunswick E3B 4R3
    Canada

    University of Toronto, Sunnybrook Health Sciences Centre
    ALS/Neuromuscular Clinic - SCIL, Room UG-35, 2075 Bayview Ave
    Toronto, Ontario M4N 3M5
    Canada

    University of Ottawa, The Rehabilitation Centre
    505 Smyth Road
    Ottawa, Ontario K1H 8M2
    Canada

    University of Western Ontario, Department of Clinical Neurological Sciences
    Motor Neuron Disease Clinic
    London, Ontario N6A 5A5
    Canada

    Queen's University, The Adult Neuromuscular Clinic, PCCC
    St. Mary's of the Lake Hospital Site, Department of Physical Medicine and Rehabilitation
    Kingston, Ontario K7L 5A2
    Canada

    University of Saskatchewan, Saskatoon City Hospital
    01 Queen Street, Room 7717 - 7th Floor
    Saskatoon, Saskatchewan S7K 0M7
    Canada

    Laval University
    CHA-Enfant-Jesus Hospital
    Quebec City, Quebec G1J 1Z4
    Canada

    University of Montreal
    CHUM (Centre Hospitalier de l'Université de Montréal) Notre-Dame Hospital
    Montreal, Quebec H2L 4M1
    Canada

    McGill University, Montreal Neurological Hospital
    3801 University, Room 205
    Montreal, Quebec H3A 2B4
    Canada

  • Study Results