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