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Trial record 13 of 29 for:    msc | Amyotrophic Lateral Sclerosis

Study to Investigate the Safety and Efficacy of Lithium in Volunteers With Amyotrophic Lateral Sclerosis (ALS)

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ClinicalTrials.gov Identifier: NCT00818389
Recruitment Status : Terminated (NINDS DSMB recommended trial be terminated for futility after reviewing an interim analysis of 84 subjects.)
First Posted : January 7, 2009
Results First Posted : April 19, 2011
Last Update Posted : April 19, 2011
Sponsor:
Collaborators:
ALS Association
ALS Society of Canada
National Institute of Neurological Disorders and Stroke (NINDS)
University of Toronto
State University of New York - Upstate Medical University
Columbia University
University of Kentucky
Information provided by:
Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE January 6, 2009
First Posted Date  ICMJE January 7, 2009
Results First Submitted Date  ICMJE May 10, 2010
Results First Posted Date  ICMJE April 19, 2011
Last Update Posted Date April 19, 2011
Study Start Date  ICMJE January 2009
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2011)
Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire (ALSFRS-R) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 6, 2009)
Primary efficacy will be assessed by analyzing disease progression as measured by the ALS Functional Rating Scale - Revised (ALSFRS-R) or death. [ Time Frame: 52 weeks of treatment followed by a telephone interview at 56 weeks ]
Change History Complete list of historical versions of study NCT00818389 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2011)
  • Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire(ALSFRS-R) [ Time Frame: 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) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2009)
Safety of long-term lithium administration as measured by adverse events (AEs), lithium levels, tolerability, physical examinations, laboratory test results, vital signs, weight/body mass index, and use of concomitant medications [ Time Frame: 52 weeks of treatment followed by a telephone interview at 56 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Investigate the Safety and Efficacy of Lithium in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
Official Title  ICMJE 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)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • 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.
  • Drug: placebo
    an inactive substance
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Lithium Carbonate
    • Drug: Riluzole
  • 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).
    Interventions:
    • Drug: Riluzole
    • Drug: placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 1, 2009)
84
Original Estimated Enrollment  ICMJE
 (submitted: January 6, 2009)
250
Actual Study Completion Date  ICMJE October 2009
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00818389
Other Study ID Numbers  ICMJE U01NS049640( U.S. NIH Grant/Contract )
3U01NS049640-04S1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merit Cudkowicz, MD, MSc, Co-Director, Neurology Clinical Trials Unit, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE
  • ALS Association
  • ALS Society of Canada
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • University of Toronto
  • State University of New York - Upstate Medical University
  • Columbia University
  • University of Kentucky
Investigators  ICMJE
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
PRS Account Massachusetts General Hospital
Verification Date March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP