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.

Study Status:

Not recruiting


Amyotrophic Lateral Sclerosis

Study Type:


Type of Intervention:


Intervention Name:

Lithium Carbonate, Riluzole, placebo



Phase 2/Phase 3

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

Merit Cudkowicz, MD, MSc, Massachusetts General Hospital, Swati Aggarwal, MD, Massachusetts General Hospital, 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:


Neals Affiliated?


Coordinating Center Contact Information

Massachusetts General Hospital

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:

Massachusetts General Hospital

Participant Duration:

56 weeks

Estimated Enrollment:


Estimated Study Start Date:

11 / 02 / 2016

Estimated Study Completion Date:

10 / 01 / 2009

Posting Last Modified Date:

04 / 19 / 2011

Date Study Added to neals.org:

01 / 07 / 2009

This study has been terminated.
(NINDS DSMB recommended trial be terminated for futility after reviewing an interim analysis of 84 subjects.)

Minimum Age:

18 Years

Maximum Age:


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.

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

Mayo Clinic-Jacksonville, Neurology Department, 4500 San Pablo Road

Jacksonville, Florida 32224
United States

University of Miami, Miller School of Medicine, 1150 NW 14th Street, Suite 609 (SCs are suite 701)

Miami, Florida 33136
United States

Indiana 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

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

New York, New York 10032
United States

SUNY Upstate Medical University, 750 E Adams St, 6610UH

Syracuse, New York 13210
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

Penn State Hershey Medical Center, Department of Neurology, H037, Pennsylvania State Hershey Medical Center

Hershey, Pennsylvania 17033
United States

Drexel University College of Medicine, 245 North 15th Street

Philadelphia, Pennsylvania 19103
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

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

Edmonton, Alberta T6G 2B7

University of British Columbia, GF Strong Rehab Centre, 4255 Laurel Street

Vancouver, British Columbia V5Z 2G9

University of Manitoba

Winnipeg, Manitoba R3T 2N2

University of New Brunswick, The Stan Cassidy Centre for Rehabilitation, 800 Priestman St.

Fredericton, New Brunswick E3B 4R3

Dalhousie University, Capital District Health Authority, Queen Elizabeth II Health Sciences Centre, P.O. Box 9000, Summer Street

Halifax, Nova Scotia B3K 6A5

McMaster University, McMaster University Medical Centre, Hamilton Health Sciences, 1200 Main Street West, Room 4U7, Box 2000

Hamilton, Ontario L8N 3Z5

Queen's University, The Adult Neuromuscular Clinic, PCCC, St. Mary's of the Lake Hospital Site, Department of Physical Medicine and Rehabilitation, 340 Union Street, Postal Bldg 3600

Kingston, Ontario K7L 5A2

University of Western Ontario, Department of Clinical Neurological Sciences, Motor Neuron Disease Clinic, 339 Windermere Road, Box 5339

London, Ontario N6A 5A5

University of Ottawa, The Rehabilitation Centre, 505 Smyth Road

Ottawa, Ontario K1H 8M2

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

Toronto, Ontario M4N 3M5

University of Montreal, CHUM (Centre Hospitalier de l'Université de Montréal) Notre-Dame Hospital 1560,Sherbrooke east street

Montreal, Quebec H2L 4M1

McGill University, Montreal Neurological Hospital, 3801 University, Room 205

Montreal, Quebec H3A 2B4

Laval University, CHA-Enfant-Jesus Hospital, 1401, 18th Street

Quebec City, Quebec G1J 1Z4

University of Saskatchewan, Saskatoon City Hospital, 701 Queen Street, Room 7717 - 7th Floor

Saskatoon, Saskatchewan S7K 0M7