Study to Investigate the Safety and Efficacy of Lithium in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Registration Number
- NCT00818389
- Lead Sponsor
- Massachusetts General Hospital
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 84
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description 2 placebo 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). 1 Lithium Carbonate 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). 1 Riluzole 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). 2 Riluzole 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).
- Primary Outcome Measures
Name Time Method Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire (ALSFRS-R) 9 months: Baseline to study termination (January 2009 - October 2009) 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
Name Time Method Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire(ALSFRS-R) 9 months: Baseline to study termination (January 2009 - October 2009) 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) 9 months: Baseline to study termination (January 2009- October 2009) Secondary efficacy was measured by comparing the rate of decline of mean VC by treatment group.
Trial Locations
- Locations (37)
Cedars-Sinai ALS Center, Neurology Specialty Clinic, 8730 Alden Drive, Thalians, E 245
🇺🇸Los Angeles, California, United States
Ohio State University, Neuromuscular Division, 1654 Uphan Drive, 417 Means Hall
🇺🇸Columbus, Ohio, United States
University of Saskatchewan, Saskatoon City Hospital, 701 Queen Street, Room 7717 - 7th Floor
🇨🇦Saskatoon, Saskatchewan, Canada
Texas Neurology, PA, 6301 Gaston Ave, Suite 400 West Tower
🇺🇸Dallas, Texas, United States
Washington University, 660 S. Euclid Ave., Box 8111 Neurology
🇺🇸St. Louis, Missouri, United States
Drexel University College of Medicine, 245 North 15th Street
🇺🇸Philadelphia, Pennsylvania, United States
Penn State Hershey Medical Center, Department of Neurology, H037, Pennsylvania State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
SUNY Upstate Medical University, 750 E Adams St, 6610UH
🇺🇸Syracuse, New York, United States
Mayo Clinic-Jacksonville, Neurology Department, 4500 San Pablo Road
🇺🇸Jacksonville, Florida, United States
University of Kentucky Medical Center, BAMC, Department of Neurology, Room A307, 1101 Veteran's Drive
🇺🇸Lexington, Kentucky, United States
Massachusetts General Hospital, 149 13th St, Room 2266
🇺🇸Charlestown, Massachusetts, United States
McMaster University, McMaster University Medical Centre, Hamilton Health Sciences, 1200 Main Street West, Room 4U7, Box 2000
🇨🇦Hamilton, Ontario, Canada
University of Vermont, Department of Neurology, 89 Beaumont Drive, Given Bldg, Room C-225
🇺🇸Burlington, Vermont, United States
Wake Forest University, ALS Center, Paul Sticht Center, Ground Floor, Medical Center Blvd
🇺🇸Winston-Salem, North Carolina, United States
University of Manitoba
🇨🇦Winnipeg, Manitoba, Canada
University of Toronto, Sunnybrook Health Sciences Centre, ALS/Neuromuscular Clinic - SCIL, Room UG-35, 2075 Bayview Ave
🇨🇦Toronto, Ontario, Canada
University of Calgary, Area 3, University of Calgary Medical Clinic, 3350 Hospital Drive NW Foothills Hosp. Grounds
🇨🇦Calgary, Alberta, Canada
University of New Brunswick, The Stan Cassidy Centre for Rehabilitation, 800 Priestman St.
🇨🇦Fredericton, New Brunswick, Canada
Columbia Univ Med Ctr, Eleanor and Lou Gehrig ALS/MDA Center, 710 West 168th St, 9th Floor
🇺🇸New York, New York, United States
Dalhousie University, Capital District Health Authority, Queen Elizabeth II Health Sciences Centre, P.O. Box 9000, Summer Street
🇨🇦Halifax, Nova Scotia, Canada
University of Montreal, CHUM (Centre Hospitalier de l'Université de Montréal) Notre-Dame Hospital 1560,Sherbrooke east street
🇨🇦Montreal, Quebec, Canada
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
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
Laval University, CHA-Enfant-Jesus Hospital, 1401, 18th Street
🇨🇦Quebec City, Quebec, Canada
University of Ottawa, The Rehabilitation Centre, 505 Smyth Road
🇨🇦Ottawa, Ontario, Canada
UCSF ALS Center, University of California San Francisco, Neurology, Box 0114, UCSF
🇺🇸San Francisco, California, United States
Phoenix Neurological Assoc., 1331 N. 7th Street, Suite 350
🇺🇸Phoenix, Arizona, United States
Hennepin County Medical Center, Dept of Neurology, 701 Part Ave S, P5-200
🇺🇸Minneapolis, Minnesota, United States
Wayne State University, Department of Neurology, 4201 St. Antoine, 8C UHC
🇺🇸Detroit, Michigan, United States
Duke University Medical Center, Box 3333
🇺🇸Durham, North Carolina, United States
University of Virginia, Department of Neurology, 3100 Hospital Drive
🇺🇸Charlottesville, Virginia, United States
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
Johns Hopkins University, Department of Neurology, 600 N. Wolfe St, Meyer 6-181
🇺🇸Baltimore, Maryland, United States
McGill University, Montreal Neurological Hospital, 3801 University, Room 205
🇨🇦Montreal, Quebec, Canada