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Study to Investigate the Safety and Efficacy of Lithium in Volunteers With Amyotrophic Lateral Sclerosis (ALS)

Information source: Massachusetts General Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Amyotrophic Lateral Sclerosis

Intervention: Lithium Carbonate (Drug); Riluzole (Drug); placebo (Drug)

Phase: Phase 2/Phase 3

Status: Terminated

Sponsored by: Massachusetts General Hospital

Official(s) and/or principal investigator(s):
Merit Cudkowicz, MD, MSc, Principal Investigator, Affiliation: Massachusetts General Hospital
Swati Aggarwal, MD, Principal Investigator, Affiliation: Massachusetts General Hospital
Lorne Zinman, MD, MSc, FRCPC, Principal Investigator, Affiliation: Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto, CA
Jinsy Andrews, MD, Principal Investigator, Affiliation: Columbia University, New York, NY


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.

Clinical Details

Official title: 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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire (ALSFRS-R)

Secondary outcome:

Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire(ALSFRS-R)

Vital Capacity (VC) (Percent of Predicted Normal)

Detailed description: 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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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


- 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.

Locations and Contacts

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

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

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

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

University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada

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

University of New Brunswick, The Stan Cassidy Centre for Rehabilitation, 800 Priestman St., Fredericton, New Brunswick E3B 4R3, Canada

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

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

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

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

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, Canada

University of Western Ontario, Department of Clinical Neurological Sciences, Motor Neuron Disease Clinic, 339 Windermere Road, Box 5339, London, Ontario N6A 5A5, Canada

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

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

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

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

University of Montreal, CHUM (Centre Hospitalier de l'Université de Montréal) Notre-Dame Hospital 1560,Sherbrooke east street, Montreal, Quebec H2L 4M1, Canada

Laval University, CHA-Enfant-Jesus Hospital, 1401, 18th Street, Quebec City, Quebec G1J 1Z4, Canada

University of Saskatchewan, Saskatoon City Hospital, 701 Queen Street, Room 7717 - 7th Floor, Saskatoon, Saskatchewan S7K 0M7, Canada

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

Additional Information

Related publications:

Fornai F, Longone P, Cafaro L, Kastsiuchenka O, Ferrucci M, Manca ML, Lazzeri G, Spalloni A, Bellio N, Lenzi P, Modugno N, Siciliano G, Isidoro C, Murri L, Ruggieri S, Paparelli A. Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2052-7. doi: 10.1073/pnas.0708022105. Epub 2008 Feb 4. Erratum in: Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16404-7.

Starting date: January 2009
Last updated: March 18, 2011

Page last updated: August 23, 2015

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