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
Disease:
Amyotrophic Lateral Sclerosis
Study Type:
Interventional
Type of Intervention:
Drug
Intervention Name:
Lithium Carbonate, Riluzole, placebo
Placebo:
Phase:
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?
Yes
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.
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:
84
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.)
(NINDS DSMB recommended trial be terminated for futility after reviewing an interim analysis of 84 subjects.)
Minimum Age:
18 Years
Maximum Age:
N/A
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
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 British Columbia, GF Strong Rehab Centre, 4255 Laurel Street
Vancouver, British Columbia
V5Z 2G9
Canada
University of Manitoba
Winnipeg, Manitoba
R3T 2N2
Canada
University of New Brunswick, The Stan Cassidy Centre for Rehabilitation, 800 Priestman St.
Fredericton, New Brunswick
E3B 4R3
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
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
University of Montreal, CHUM (Centre Hospitalier de l'Université de Montréal) Notre-Dame Hospital 1560,Sherbrooke east street
Montreal, Quebec
H2L 4M1
Canada
McGill University, Montreal Neurological Hospital, 3801 University, Room 205
Montreal, Quebec
H3A 2B4
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