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

NCT ID: NCT00818389

Last Updated: 2011-04-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2009-10-31

Brief Summary

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.

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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Participants randomized to lithium/riluzole (randomization is 1:1 lithium/riluzole to placebo/riluzole, i.e., participants have an equal chance of getting randomized to lithium vs. placebo).

Group Type: ACTIVE_COMPARATOR

Lithium Carbonate

Intervention Type: DRUG

Participants will receive capsules that contain 150 milligrams (mg) lithium carbonate. Participants will be randomized to lithium/riluzole or placebo/riluzole and treated for 52 weeks. Participants originally randomized to placebo who fail (progress) will crossover to lithium for the remainder of the trial.

Riluzole

Intervention Type: DRUG

All participants enrolled in this study will be taking a stable dose of riluzole 50 milligrams (mg) by mouth (PO) twice per day (BID) for at least 30 days prior to screening.

2

Participants randomized to placebo/riluzole (randomization is 1:1 lithium/riluzole to placebo/riluzole, i.e., participants have an equal chance of getting randomized to lithium vs. placebo).

Group Type: PLACEBO_COMPARATOR

Riluzole

Intervention Type: DRUG

All participants enrolled in this study will be taking a stable dose of riluzole 50 milligrams (mg) by mouth (PO) twice per day (BID) for at least 30 days prior to screening.

placebo

Intervention Type: DRUG

an inactive substance

Interventions

Lithium Carbonate

Participants will receive capsules that contain 150 milligrams (mg) lithium carbonate. Participants will be randomized to lithium/riluzole or placebo/riluzole and treated for 52 weeks. Participants originally randomized to placebo who fail (progress) will crossover to lithium for the remainder of the trial.

Intervention Type: DRUG

Riluzole

All participants enrolled in this study will be taking a stable dose of riluzole 50 milligrams (mg) by mouth (PO) twice per day (BID) for at least 30 days prior to screening.

Intervention Type: DRUG

placebo

an inactive substance

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ALS Association

OTHER

Sponsor Role: collaborator

ALS Society of Canada

OTHER_GOV

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

University of Toronto

OTHER

Sponsor Role: collaborator

State University of New York - Upstate Medical University

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: collaborator

University of Kentucky

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Massachusetts General Hospital

Principal Investigators

Merit Cudkowicz, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Swati Aggarwal, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Lorne Zinman, MD, MSc, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto, CA

Jinsy Andrews, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University, New York, NY

Locations

Phoenix Neurological Assoc., 1331 N. 7th Street, Suite 350

Phoenix, Arizona, United States

Cedars-Sinai ALS Center, Neurology Specialty Clinic, 8730 Alden Drive, Thalians, E 245

Los Angeles, California, United States

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

San Francisco, California, United States

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

Jacksonville, Florida, United States

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

Miami, Florida, United States

Indiana University, Department of Neurology, 1050 Wishard Blvd, RG 6

Indianapolis, Indiana, United States

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

Lexington, Kentucky, United States

Johns Hopkins University, Department of Neurology, 600 N. Wolfe St, Meyer 6-181

Baltimore, Maryland, United States

Massachusetts General Hospital, 149 13th St, Room 2266

Charlestown, Massachusetts, United States

Wayne State University, Department of Neurology, 4201 St. Antoine, 8C UHC

Detroit, Michigan, United States

Hennepin County Medical Center, Dept of Neurology, 701 Part Ave S, P5-200

Minneapolis, Minnesota, United States

Washington University, 660 S. Euclid Ave., Box 8111 Neurology

St Louis, Missouri, United States

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

New York, New York, United States

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

Syracuse, New York, United States

Duke University Medical Center, Box 3333

Durham, North Carolina, United States

Wake Forest University, ALS Center, Paul Sticht Center, Ground Floor, Medical Center Blvd

Winston-Salem, North Carolina, United States

Ohio State University, Neuromuscular Division, 1654 Uphan Drive, 417 Means Hall

Columbus, Ohio, United States

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

Hershey, Pennsylvania, United States

Drexel University College of Medicine, 245 North 15th Street

Philadelphia, Pennsylvania, United States

Texas Neurology, PA, 6301 Gaston Ave, Suite 400 West Tower

Dallas, Texas, United States

University of Vermont, Department of Neurology, 89 Beaumont Drive, Given Bldg, Room C-225

Burlington, Vermont, United States

University of Virginia, Department of Neurology, 3100 Hospital Drive

Charlottesville, Virginia, United States

University of Calgary, Area 3, University of Calgary Medical Clinic, 3350 Hospital Drive NW Foothills Hosp. Grounds

Calgary, Alberta, Canada

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

Edmonton, Alberta, Canada

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

Vancouver, British Columbia, Canada

University of Manitoba

Winnipeg, Manitoba, Canada

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

Fredericton, New Brunswick, Canada

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

Halifax, Nova Scotia, Canada

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

Hamilton, Ontario, 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, Canada

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

London, Ontario, Canada

University of Ottawa, The Rehabilitation Centre, 505 Smyth Road

Ottawa, Ontario, Canada

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

Toronto, Ontario, Canada

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

Montreal, Quebec, Canada

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

Montreal, Quebec, Canada

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

Québec, Quebec, Canada

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

Saskatoon, Saskatchewan, Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

PMID: 18250315 (View on PubMed)

Din Abdul Jabbar MA, Guo L, Guo Y, Simmons Z, Pioro EP, Ramasamy S, Yeo CJJ. Describing and characterising variability in ALS disease progression. Amyotroph Lateral Scler Frontotemporal Degener. 2024 Feb;25(1-2):34-45. doi: 10.1080/21678421.2023.2260838. Epub 2024 Jan 23.

Reference Type: DERIVED

PMID: 37794802 (View on PubMed)

Aggarwal SP, Zinman L, Simpson E, McKinley J, Jackson KE, Pinto H, Kaufman P, Conwit RA, Schoenfeld D, Shefner J, Cudkowicz M; Northeast and Canadian Amyotrophic Lateral Sclerosis consortia. Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010 May;9(5):481-8. doi: 10.1016/S1474-4422(10)70068-5. Epub 2010 Apr 1.

Reference Type: DERIVED

PMID: 20363190 (View on PubMed)

Other Identifiers

3U01NS049640-04S1

Identifier Type: NIH

Identifier Source: secondary_id

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U01NS049640

Identifier Type: NIH

Identifier Source: org_study_id

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