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

NCT00818389 | Terminated Phase 2 Results DMC

• 2 other identifiers: U01NS0496403U01NS049640-04S1
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 37

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic lateral sclerosis; ALS; Lou Gehrig's disease; riluzole; lithium; neurodegeneration

Outcome Measures

Primary Outcomes (1)

• Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire (ALSFRS-R)

  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.

  9 months: Baseline to study termination (January 2009 - October 2009)

Secondary Outcomes (2)

• Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire(ALSFRS-R)

  9 months: Baseline to study termination (January 2009 - October 2009)

• Vital Capacity (VC) (Percent of Predicted Normal)

  9 months: Baseline to study termination (January 2009- October 2009)

Study Arms (2)

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 Carbonate; Drug: Riluzole

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; Drug: placebo

Interventions

Lithium Carbonate DRUG

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.

1

Riluzole DRUG

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.

1; 2

placebo DRUG

an inactive substance

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• ALS Association: collaborator
• ALS Society of Canada: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• University of Toronto: collaborator
• State University of New York - Upstate Medical University: collaborator
• Columbia University: collaborator
• University of Kentucky: collaborator

Study Sites (37)

Phoenix Neurological Assoc., 1331 N. 7th Street, Suite 350

Phoenix, Arizona, 85006, United States

Location

Cedars-Sinai ALS Center, Neurology Specialty Clinic, 8730 Alden Drive, Thalians, E 245

Los Angeles, California, 90048, United States

Location

UCSF ALS Center, University of California San Francisco, Neurology, Box 0114, UCSF

San Francisco, California, 94143, United States

Location

Mayo Clinic-Jacksonville, Neurology Department, 4500 San Pablo Road

Jacksonville, Florida, 32224, United States

Location

University of Miami, Miller School of Medicine, 1150 NW 14th Street, Suite 609 (SCs are suite 701)

Miami, Florida, 33136, United States

Location

Indiana University, Department of Neurology, 1050 Wishard Blvd, RG 6

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky Medical Center, BAMC, Department of Neurology, Room A307, 1101 Veteran's Drive

Lexington, Kentucky, 40502', United States

Location

Johns Hopkins University, Department of Neurology, 600 N. Wolfe St, Meyer 6-181

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital, 149 13th St, Room 2266

Charlestown, Massachusetts, 02129, United States

Location

Wayne State University, Department of Neurology, 4201 St. Antoine, 8C UHC

Detroit, Michigan, 48201, United States

Location

Hennepin County Medical Center, Dept of Neurology, 701 Part Ave S, P5-200

Minneapolis, Minnesota, 55415, United States

Location

Washington University, 660 S. Euclid Ave., Box 8111 Neurology

St Louis, Missouri, 63110, United States

Location

Columbia Univ Med Ctr, Eleanor and Lou Gehrig ALS/MDA Center, 710 West 168th St, 9th Floor

New York, New York, 10032, United States

Location

SUNY Upstate Medical University, 750 E Adams St, 6610UH

Syracuse, New York, 13210, United States

Location

Duke University Medical Center, Box 3333

Durham, North Carolina, 27707, United States

Location

Wake Forest University, ALS Center, Paul Sticht Center, Ground Floor, Medical Center Blvd

Winston-Salem, North Carolina, 27157-1078, United States

Location

Ohio State University, Neuromuscular Division, 1654 Uphan Drive, 417 Means Hall

Columbus, Ohio, 43210, United States

Location

Penn State Hershey Medical Center, Department of Neurology, H037, Pennsylvania State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Drexel University College of Medicine, 245 North 15th Street

Philadelphia, Pennsylvania, 19103, United States

Location

Texas Neurology, PA, 6301 Gaston Ave, Suite 400 West Tower

Dallas, Texas, 75214, United States

Location

University of Vermont, Department of Neurology, 89 Beaumont Drive, Given Bldg, Room C-225

Burlington, Vermont, 05405, United States

Location

University of Virginia, Department of Neurology, 3100 Hospital Drive

Charlottesville, Virginia, 22908, United States

Location

University of Calgary, Area 3, University of Calgary Medical Clinic, 3350 Hospital Drive NW Foothills Hosp. Grounds

Calgary, Alberta, T2N 4N1, Canada

Location

University of Alberta, Division of Neurology, Dept of Medicine, 2E3.17 Walter C. MacKenzie Health Sciences Center

Edmonton, Alberta, T6G 2B7, Canada

Location

University of British Columbia, GF Strong Rehab Centre, 4255 Laurel Street

Vancouver, British Columbia, V5Z 2G9, Canada

Location

University of Manitoba

Winnipeg, Manitoba, R3T 2N2, Canada

Location

University of New Brunswick, The Stan Cassidy Centre for Rehabilitation, 800 Priestman St.

Fredericton, New Brunswick, E3B 4R3, Canada

Location

Dalhousie University, Capital District Health Authority, Queen Elizabeth II Health Sciences Centre, P.O. Box 9000, Summer Street

Halifax, Nova Scotia, B3K 6A5, Canada

Location

McMaster University, McMaster University Medical Centre, Hamilton Health Sciences, 1200 Main Street West, Room 4U7, Box 2000

Hamilton, Ontario, L8N 3Z5, Canada

Location

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, K7L 5A2, Canada

Location

University of Western Ontario, Department of Clinical Neurological Sciences, Motor Neuron Disease Clinic, 339 Windermere Road, Box 5339

London, Ontario, N6A 5A5, Canada

Location

University of Ottawa, The Rehabilitation Centre, 505 Smyth Road

Ottawa, Ontario, K1H 8M2, Canada

Location

University of Toronto, Sunnybrook Health Sciences Centre, ALS/Neuromuscular Clinic - SCIL, Room UG-35, 2075 Bayview Ave

Toronto, Ontario, M4N 3M5, Canada

Location

University of Montreal, CHUM (Centre Hospitalier de l'Université de Montréal) Notre-Dame Hospital 1560,Sherbrooke east street

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University, Montreal Neurological Hospital, 3801 University, Room 205

Montreal, Quebec, H3A 2B4, Canada

Location

Laval University, CHA-Enfant-Jesus Hospital, 1401, 18th Street

Québec, Quebec, G1J 1Z4, Canada

Location

University of Saskatchewan, Saskatoon City Hospital, 701 Queen Street, Room 7717 - 7th Floor

Saskatoon, Saskatchewan, S7K 0M7, Canada

Location

Related Publications (3)

• Fornai F, Longone P, Cafaro L, Kastsiuchenka O, Ferrucci M, Manca ML, Lazzeri G, Spalloni A, Bellio N, Lenzi P, Modugno N, Siciliano G, Isidoro C, Murri L, Ruggieri S, Paparelli A. Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2052-7. doi: 10.1073/pnas.0708022105. Epub 2008 Feb 4.

  PMID: 18250315 BACKGROUND

• Din Abdul Jabbar MA, Guo L, Guo Y, Simmons Z, Pioro EP, Ramasamy S, Yeo CJJ. Describing and characterising variability in ALS disease progression. Amyotroph Lateral Scler Frontotemporal Degener. 2024 Feb;25(1-2):34-45. doi: 10.1080/21678421.2023.2260838. Epub 2024 Jan 23.

  PMID: 37794802 DERIVED

• Aggarwal SP, Zinman L, Simpson E, McKinley J, Jackson KE, Pinto H, Kaufman P, Conwit RA, Schoenfeld D, Shefner J, Cudkowicz M; Northeast and Canadian Amyotrophic Lateral Sclerosis consortia. Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010 May;9(5):481-8. doi: 10.1016/S1474-4422(10)70068-5. Epub 2010 Apr 1.

  PMID: 20363190 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Nerve Degeneration

Interventions

Lithium Carbonate; Riluzole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Elizabeth Simpson
• Organization: Massachusetts General Hospital

esimpson1@partners.org

617-726-3430

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 6, 2009
• First Posted: January 7, 2009
• Study Start: January 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: April 19, 2011
• Results First Posted: April 19, 2011

Record last verified: 2011-03

Locations

CA (15); US (22)