Study to Investigate the Safety and Efficacy of Lithium in Volunteers With ALS
This study is not yet open for participant recruitment.
Verified by National Institute of Neurological Disorders and Stroke (NINDS), January 2009
Sponsors and Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
ALS Association
ALS Society of Canada
Massachusetts General Hospital
University of Toronto
State University of New York - Upstate Medical University
Columbia University
University of Kentucky Medical Center

Information provided by: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT00818389

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
ALS
Drug: Lithium
Drug: Riluzole
Drug: placebo
Phase II
Phase III




Genetics Home Reference related topics: amyotrophic lateral sclerosis
MedlinePlus related topics: Amyotrophic Lateral Sclerosis
Drug Information available for: Riluzole Lithium carbonate Lithium citrate
U.S. FDA Resources
Study Type:Interventional
Study Design:Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study
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)


Further study details as provided by National Institute of Neurological Disorders and Stroke (NINDS):


Primary Outcome Measures:
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 ] [ Designated as safety issue: Yes ]



Secondary Outcome Measures:
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 ] [ Designated as safety issue: Yes ]



Estimated Enrollment:250
Study Start Date:January 2009
Estimated Study Completion Date:July 2011
Estimated Primary Completion Date:July 2010 (Final data collection date for primary outcome measure)


Arms Assigned Interventions
1: Active Comparator
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
Participants will receive capsules that contain 150 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 mg PO BID for at least 30 days prior to screening.
2: Placebo Comparator
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 mg PO 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 ALS 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 50mg bid for at least 30 days prior to screening
Vital capacity (VC) equal to or more than 60% predicted value for gender, height and age at the Screening Visit
Creatinine <1.5 mg/dl (133 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; 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), TSH > 20% above the upper limit; Presence of any clinically significant conduction abnormalities on ECG; or Lactating or have a positive serum pregnancy test at the Screening Visit.
Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00818389


Contacts
Contact: Liz Simpson 617-726-3430 esimpson1@partners.org

Show 37 Study Locations

Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
ALS Association
ALS Society of Canada
Massachusetts General Hospital
University of Toronto
State University of New York - Upstate Medical University
Columbia University
University of Kentucky Medical Center
Investigators
Principal Investigator: Merit Cudkowicz, MD, MSc Massachusetts General Hospital
Principal Investigator: Swati Aggarwal, MD Massachusetts General Hospital

More Information

Responsible Party:Massachusetts General Hospital ( Merit Cudkowicz, MD, MSc, Co-Director, Neurology Clinical Trials Unit )
Study ID Numbers:U01NS049640, LALS-001, 3U01NS049640-04S1
First Received:January 6, 2009
Last Updated:January 6, 2009
ClinicalTrials.gov Identifier:NCT00818389 [history]
Health Authority:United States: Federal Government; Canada: Health Canada

Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS):
Amyotrophic lateral sclerosis
ALS
Lou Gehrig's disease
riluzole
lithium
neurodegeneration


Study placed in the following topic categories:
Riluzole
Excitatory Amino Acids
Spinal Cord Diseases
Central Nervous System Diseases
Lithium Carbonate
Sclerosis
Degenerative motor system disease
Neurodegenerative Diseases
Motor neuron disease
Nerve Degeneration
Amyotrophic lateral sclerosis
Neuromuscular Diseases
Amyotrophic Lateral Sclerosis
Lou Gehrig's disease
Motor Neuron Disease
Lithium


Additional relevant MeSH terms:
Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Excitatory Amino Acid Agents
Enzyme Inhibitors
Antipsychotic Agents
Antimanic Agents
Protective Agents
Neuroprotective Agents
Pharmacologic Actions
Pathologic Processes
Therapeutic Uses
Central Nervous System Agents
Anticonvulsants
Antidepressive Agents
Excitatory Amino Acid Antagonists


ClinicalTrials.gov processed this record on January 09, 2009

http://clinicaltrials.gov/ct2/show/N...ty+of+michigan