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Amyotrophic Lateral SclerosisPhase 2/3NCT00818389

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

A Phase 2/3 study testing Lithium Carbonate and Riluzole in people with Amyotrophic Lateral Sclerosis, run by Massachusetts General Hospital at 37 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Amyotrophic Lateral Sclerosis
What is being tested?
Lithium Carbonate and Riluzole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
84 participants
Where
37 sitesin 2 countries
Study dates
Jan 2009to Oct 2009
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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.

Trial locations and contacts

37 sites in 2 countries.

37 sites in 2 countries

United States22 sites

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

    Baltimore, Maryland, 21287

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

    Burlington, Vermont, 05405

  • Massachusetts General Hospital, 149 13th St, Room 2266

    Charlestown, Massachusetts, 02129

  • University of Virginia, Department of Neurology, 3100 Hospital Drive

    Charlottesville, Virginia, 22908

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

    Columbus, Ohio, 43210

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

    Dallas, Texas, 75214

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

    Detroit, Michigan, 48201

  • Duke University Medical Center, Box 3333

    Durham, North Carolina, 27707

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

    Hershey, Pennsylvania, 17033

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

    Indianapolis, Indiana, 46202

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

    Jacksonville, Florida, 32224

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

    Lexington, Kentucky, 40502'

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

    Los Angeles, California, 90048

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

    Miami, Florida, 33136

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

    Minneapolis, Minnesota, 55415

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

    New York, New York, 10032

  • Drexel University College of Medicine, 245 North 15th Street

    Philadelphia, Pennsylvania, 19103

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

    Phoenix, Arizona, 85006

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

    San Francisco, California, 94143

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

    St Louis, Missouri, 63110

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

    Syracuse, New York, 13210

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

    Winston-Salem, North Carolina, 27157-1078

Other trials in United States

Canada15 sites

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

    Calgary, Alberta, T2N 4N1

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

    Edmonton, Alberta, T6G 2B7

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

    Fredericton, New Brunswick, E3B 4R3

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

    Halifax, Nova Scotia, B3K 6A5

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

    Hamilton, Ontario, L8N 3Z5

  • 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

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

    London, Ontario, N6A 5A5

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

    Montreal, Quebec, H2L 4M1

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

    Montreal, Quebec, H3A 2B4

  • University of Ottawa, The Rehabilitation Centre, 505 Smyth Road

    Ottawa, Ontario, K1H 8M2

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

    Québec, Quebec, G1J 1Z4

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

    Saskatoon, Saskatchewan, S7K 0M7

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

    Toronto, Ontario, M4N 3M5

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

    Vancouver, British Columbia, V5Z 2G9

  • University of Manitoba

    Winnipeg, Manitoba, R3T 2N2

Other trials in Canada

About this 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)

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.

Read the 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.

Being tested
Lithium Carbonate, Riluzole, placebo
Keywords
Amyotrophic lateral sclerosis, ALS, Lou Gehrig's disease, riluzole, lithium, neurodegeneration
Medical subject headings
Amyotrophic Lateral Sclerosis, Nerve Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lithium CarbonateDrug

    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.

  • RiluzoleDrug

    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.

  • placeboDrug

    an inactive substance

Study groups in NCT00818389
Study groupRoleWhat they receive
1Active comparatorParticipants 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).
Receives: Drug: Lithium Carbonate; Drug: Riluzole
2Placebo comparatorParticipants 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).
Receives: Drug: Riluzole; Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (2)

  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. Secondary efficacy was evaluated by comparing the mean rate of decline of ALSFRS-R score by treatment group.

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

  2. Vital Capacity (VC) (Percent of Predicted Normal)

    Secondary efficacy was measured by comparing the rate of decline of mean VC by treatment group.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2009 (estimated)
  2. Study startJan 2009
  3. Primary completionOct 2009
  4. Study completionOct 2009

Why it stopped: NINDS DSMB recommended trial be terminated for futility after reviewing an interim analysis of 84 subjects.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00818389
Sponsor's protocol ID
U01NS049640
Other IDs
3U01NS049640-04S1
Status last verified
Mar 2011
First submitted
6 Jan 2009
Last updated
19 Apr 2011
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 18250315

  • 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.

    PubMed 37794802

  • 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.

    PubMed 20363190

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Lithium Carbonate and Riluzole in people with Amyotrophic Lateral Sclerosis, run by Massachusetts General Hospital at 37 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised Questionnaire (ALSFRS-R) (time frame: 9 months: Baseline to study termination (January 2009 - October 2009)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00818389, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2011.

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