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
Results First Received: May 10, 2010  
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
Condition: Amyotrophic Lateral Sclerosis
Interventions: Drug: Lithium Carbonate
Drug: Riluzole
Drug: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Between January 2009 to June 2009, 97 patients were screened and 84 subjects were randomized at 21 clinical sites; 11 in the United States and 10 in Canada. All sites were members of the Northeast ALS Consortium (NEALS) and/or the Canadian ALS Consortium (CALS).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All patients were required to be on a stable dose of riluzole for at least 30 days prior to screening. 13 subjects failed screening: 3 due to low lung function test results, 3 due to prohibited medications,3 due to study closure, 2 due to abnormal lab test results and 1 due to death unrelated to the study.

Reporting Groups
  Description
Lithium + Riluzole Subjects randomized to lithium + riluzole were required to be taking riluzole 50 milligrams (mg) twice per day at least 30 days prior to the screening visit and during the trial. Lithium carbonate and matching placebo were supplied in 150 mg capsules. Dosing started at 450 mg/day (1 capsule taken in the a.m. and 2 capsules taken in the p.m.), titrated to maintain plasma lithium levels of 0.4 - 0.8 milliequivalent per liter (mEq/L). The number of capsules taken per day was titrated individually for each patient based on blood testing to maintain plasma levels of lithium = 04. - 0.8 milliequivalent per liter (mEq/L).
Placebo + Riluzole Participants randomized to placebo + riluzole were required to be taking riluzole 50 milligrams (mg) twice per day at least 30 days prior to the screening visit and during the trial. Matching placebo was supplied in 150 mg capsules. Dosing started at 450 mg/day (1 capsule in the a.m. and 2 capsules in the p.m). Paired sham dosage modifications were made for placebo subjects, i.e. all subjects randomized to placebo were 'paired' with a lithium subject and underwent identical dosage changes to maintain blinding.

Participant Flow:   Overall Study
    Lithium + Riluzole     Placebo + Riluzole  
STARTED     40     44  
COMPLETED     36 [1]   38 [2]
NOT COMPLETED     4     6  
Death                 1                 3  
ALS Disease Progression                 1                 0  
Withdrawal by Subject                 2                 2  
Adverse Event                 0                 1  
[1] 4 subjects terminated study early before 1st interim analysis. Study terminated early for futility.
[2] 6 subjects terminated study early before 1st interim analysis. Study terminated early for futility.



  Baseline Characteristics


  Outcome Measures
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1.  Primary:   Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire (ALSFRS-R)   [ Time Frame: 9 months: Baseline to study termination (January 2009 - October 2009) ]

2.  Secondary:   Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire(ALSFRS-R)   [ Time Frame: 9 months: Baseline to study termination (January 2009 - October 2009) ]

3.  Secondary:   Vital Capacity (VC) (Percent of Predicted Normal)   [ Time Frame: 9 months: Baseline to study termination (January 2009- October 2009) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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