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

This study has been terminated.
(NINDS DSMB recommended trial be terminated for futility after reviewing an interim analysis of 84 subjects.)
Sponsor:
Collaborators:
ALS Association
ALS Society of Canada
University of Toronto
State University of New York - Upstate Medical University
Columbia University
University of Kentucky
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00818389
First received: January 6, 2009
Last updated: March 18, 2011
Last verified: March 2011
  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.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: Lithium Carbonate
Drug: Riluzole
Drug: placebo
Phase 2
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire (ALSFRS-R) [ Time Frame: 9 months: Baseline to study termination (January 2009 - October 2009) ] [ Designated as safety issue: No ]
    ALSFRS-R is a self-administered ordinal rating scale questionnaire (rating 0-4 for each question,4 is most functional,0-48 total)of 12 functional activities. The most functional total score is 48. ALSFRS-R done at baseline and weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 & 52, dependent on enrollment duration. Number of subjects who failed by treatment group was evaluated. Failure was defined as 6-point drop in ALSFRS-R or death from baseline.


Secondary Outcome Measures:
  • Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire(ALSFRS-R) [ Time Frame: 9 months: Baseline to study termination (January 2009 - October 2009) ] [ Designated as safety issue: No ]
    ALSFRS-R is a self-administered ordinal rating scale questionnaire (rating 0-4 for each question,4 is most functional,0-48 total)of 12 functional activities. The most functional total score is 48. ALSFRS-R done at baseline and weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 & 52, dependent on enrollment duration. Secondary efficacy was evaluated by comparing the mean rate of decline of ALSFRS-R score by treatment group.

  • Vital Capacity (VC) (Percent of Predicted Normal) [ Time Frame: 9 months: Baseline to study termination (January 2009- October 2009) ] [ Designated as safety issue: No ]
    Secondary efficacy was measured by comparing the rate of decline of mean VC by treatment group.


Enrollment: 84
Study Start Date: January 2009
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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).
Drug: 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.
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.
Placebo Comparator: 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).
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.
Drug: placebo
an inactive substance

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00818389

  Hide Study Locations
Locations
United States, Arizona
Phoenix Neurological Assoc., 1331 N. 7th Street, Suite 350
Phoenix, Arizona, United States, 85006
United States, California
Cedars-Sinai ALS Center, Neurology Specialty Clinic, 8730 Alden Drive, Thalians, E 245
Los Angeles, California, United States, 90048
UCSF ALS Center, University of California San Francisco, Neurology, Box 0114, UCSF
San Francisco, California, United States, 94143
United States, Florida
Mayo Clinic-Jacksonville, Neurology Department, 4500 San Pablo Road
Jacksonville, Florida, United States, 32224
University of Miami, Miller School of Medicine, 1150 NW 14th Street, Suite 609 (SCs are suite 701)
Miami, Florida, United States, 33136
United States, Indiana
Indiana University, Department of Neurology, 1050 Wishard Blvd, RG 6
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University of Kentucky Medical Center, BAMC, Department of Neurology, Room A307, 1101 Veteran's Drive
Lexington, Kentucky, United States, 40502`
United States, Maryland
Johns Hopkins University, Department of Neurology, 600 N. Wolfe St, Meyer 6-181
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital, 149 13th St, Room 2266
Charlestown, Massachusetts, United States, 02129
United States, Michigan
Wayne State University, Department of Neurology, 4201 St. Antoine, 8C UHC
Detroit, Michigan, United States, 48201
United States, Minnesota
Hennepin County Medical Center, Dept of Neurology, 701 Part Ave S, P5-200
Minneapolis, Minnesota, United States, 55415
United States, Missouri
Washington University, 660 S. Euclid Ave., Box 8111 Neurology
St. Louis, Missouri, United States, 63110
United States, New York
Columbia Univ Med Ctr, Eleanor and Lou Gehrig ALS/MDA Center, 710 West 168th St, 9th Floor
New York, New York, United States, 10032
SUNY Upstate Medical University, 750 E Adams St, 6610UH
Syracuse, New York, United States, 13210
United States, North Carolina
Duke University Medical Center, Box 3333
Durham, North Carolina, United States, 27707
Wake Forest University, ALS Center, Paul Sticht Center, Ground Floor, Medical Center Blvd
Winston-Salem, North Carolina, United States, 27157-1078
United States, Ohio
Ohio State University, Neuromuscular Division, 1654 Uphan Drive, 417 Means Hall
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Penn State Hershey Medical Center, Department of Neurology, H037, Pennsylvania State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Drexel University College of Medicine, 245 North 15th Street
Philadelphia, Pennsylvania, United States, 19103
United States, Texas
Texas Neurology, PA, 6301 Gaston Ave, Suite 400 West Tower
Dallas, Texas, United States, 75214
United States, Vermont
University of Vermont, Department of Neurology, 89 Beaumont Drive, Given Bldg, Room C-225
Burlington, Vermont, United States, 05405
United States, Virginia
University of Virginia, Department of Neurology, 3100 Hospital Drive
Charlottesville, Virginia, United States, 22908
Canada, Alberta
University of Calgary, Area 3, University of Calgary Medical Clinic, 3350 Hospital Drive NW Foothills Hosp. Grounds
Calgary, Alberta, Canada, T2N 4N1
University of Alberta, Division of Neurology, Dept of Medicine, 2E3.17 Walter C. MacKenzie Health Sciences Center
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
University of British Columbia, GF Strong Rehab Centre, 4255 Laurel Street
Vancouver, British Columbia, Canada, V5Z 2G9
Canada, Manitoba
University of Manitoba
Winnipeg, Manitoba, Canada, R3T 2N2
Canada, New Brunswick
University of New Brunswick, The Stan Cassidy Centre for Rehabilitation, 800 Priestman St.
Fredericton, New Brunswick, Canada, E3B 4R3
Canada, Nova Scotia
Dalhousie University, Capital District Health Authority, Queen Elizabeth II Health Sciences Centre, P.O. Box 9000, Summer Street
Halifax, Nova Scotia, Canada, B3K 6A5
Canada, Ontario
McMaster University, McMaster University Medical Centre, Hamilton Health Sciences, 1200 Main Street West, Room 4U7, Box 2000
Hamilton, Ontario, Canada, 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, Canada, K7L 5A2
University of Western Ontario, Department of Clinical Neurological Sciences, Motor Neuron Disease Clinic, 339 Windermere Road, Box 5339
London, Ontario, Canada, N6A 5A5
University of Ottawa, The Rehabilitation Centre, 505 Smyth Road
Ottawa, Ontario, Canada, K1H 8M2
University of Toronto, Sunnybrook Health Sciences Centre, ALS/Neuromuscular Clinic - SCIL, Room UG-35, 2075 Bayview Ave
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
McGill University, Montreal Neurological Hospital, 3801 University, Room 205
Montreal, Quebec, Canada, H3A 2B4
University of Montreal, CHUM (Centre Hospitalier de l'Université de Montréal) Notre-Dame Hospital 1560,Sherbrooke east street
Montreal, Quebec, Canada, H2L 4M1
Laval University, CHA-Enfant-Jesus Hospital, 1401, 18th Street
Quebec City, Quebec, Canada, G1J 1Z4
Canada, Saskatchewan
University of Saskatchewan, Saskatoon City Hospital, 701 Queen Street, Room 7717 - 7th Floor
Saskatoon, Saskatchewan, Canada, S7K 0M7
Sponsors and Collaborators
Massachusetts General Hospital
ALS Association
ALS Society of Canada
University of Toronto
State University of New York - Upstate Medical University
Columbia University
University of Kentucky
Investigators
Principal Investigator: Merit Cudkowicz, MD, MSc Massachusetts General Hospital
Principal Investigator: Swati Aggarwal, MD Massachusetts General Hospital
Principal Investigator: Lorne Zinman, MD, MSc, FRCPC Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto, CA
Principal Investigator: Jinsy Andrews, MD Columbia University, New York, NY
  More Information

Publications:
Fornai, F., et al., Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci USA, 2008. 105(6): p. 2052-7.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merit Cudkowicz, MD, MSc, Co-Director, Neurology Clinical Trials Unit, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00818389     History of Changes
Other Study ID Numbers: U01NS049640, 3U01NS049640-04S1
Study First Received: January 6, 2009
Results First Received: May 10, 2010
Last Updated: March 18, 2011
Health Authority: United States: Federal Government
Canada: Health Canada

Keywords provided by Massachusetts General Hospital:
Amyotrophic lateral sclerosis
ALS
Lou Gehrig's disease
riluzole
lithium
neurodegeneration

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Lithium
Lithium Carbonate
Riluzole
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticonvulsants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on September 18, 2014