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Trial record 1 of 268 for:    Amyotrophic Lateral Sclerosis (ALS)
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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

  Show 37 Study Locations
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:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Central Nervous System Diseases
Metabolic Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Pathologic Processes
Proteostasis Deficiencies
Spinal Cord Diseases
TDP-43 Proteinopathies
Lithium
Lithium Carbonate
Riluzole
Anticonvulsants
Antidepressive Agents
Antimanic Agents
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on November 25, 2014