A Multi-Center Controlled Screening Trial of Safety and Efficacy of Lithium Carbonate in Subjects With Amyotrophic Lateral Sclerosis (ALS) (Lithium)

This is a Phase II screening study of lithium carbonate in ALS. The purpose of this study is to find out if lithium carbonate is safe to be used in people with ALS and if it can slow the progression of the disease. Since there is no placebo in this study, all patients will be taking lithium carbonate.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: lithium carbonate

Detailed Description

This is a Phase II Screening study. There is no placebo (inactive or 'fake' drug) in this study, meaning that all participants will be taking lithium carbonate. The purpose of this study is to find out if lithium carbonate is safe to be used in people with ALS and if it can slow the progression of the disease.

A recent article was published in a highly regarded medical journal that showed a positive effect of lithium carbonate on an ALS type mouse. The researchers then studied a very small number of people with ALS, giving 16 people lithium carbonate with riluzole and giving 28 people only riluzole. The people who took lithium remained stronger for a considerably longer period of time. However, the study was very small and we cannot really tell if lithium works unless a larger study is performed. It is not well understood why lithium carbonate might be helpful but it is believed that it may play a role in protecting the motor nerves from the damage of ALS.

If you choose to participate, you will need to go to your study clinic for research study visits 7 times in one year and you will have 4 telephone interviews during that time. These visits and phone calls could take up to 17 hours in total.

Caution: Lithium is an FDA approved drug used for some psychiatric disorders. It is not FDA approved for ALS. Lithium has many potentially serious side effects and must only be taken under close supervision of your physician.

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Neuromuscular Research Center
    • Orange, California, United States, 92868
      • UC Irvine MDA/ALS & Neuromuscular Center
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Department of Neurology
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence ALS Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • University of Pennsylvania Neurological Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Methodist Neurological Institute
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Clinical Neurosciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of laboratory-supported probable, probable, or definite ALS
• Vital capacity of at least 75% of predicted
• Onset of weakness within 3 years prior to enrollment
• If patients are on riluzole, they must be on a stable dose for at least 30 days prior to baseline visit
• Women of childbearing potential must be surgically sterile or using an effective method of birth control and have a negative pregnancy test
• Willing and able to give informed consent

Exclusion Criteria:

• Diagnosis of other neurodegenerative disease
• Need tracheotomy ventilation or non-invasive ventilation 23 or more hours/day
• Clinically significant history of any unstable medical condition in past 30 days
• History of renal
• History of liver disease
• Current pregnancy or lactation
• Use of lithium within thirty days of enrollment
• Significantly limited mental capacity
• History of recent drug or alcohol abuse
• Use of any investigational drug within 30 days prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lithium carbonate	Drug: lithium carbonate; The dosage of lithium carbonate will be adjusted for each individual. The maximum dose is 450mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised)	This questionnaire has 12 questions about the patient's ability to complete certain daily activities. There are three questions each about the mouth area, arms, legs, and breathing. A normal score is 48 with each question scored at 0 (worst) to 4 (normal function). In research studies, the change in slope is measured in number of points changed per month. Maximum possible=48 (normal) Minimum=0 (severe dysfunction)	Baseline, Month 1,3,4.5,6,7.5,9,10.5,12,13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital Capacity	Vital Capacity (VC) is a breathing test in which the patient is asked to take a deep breath and then blow out all of the breath through a tube. The volume is measured in number of liters. It is converted to a percent predicted for the patient's age, height, and gender.	Screen, Baseline, Month 1,3,6,9,12

Collaborators and Investigators

• Sponsor: Forbes Norris MDA/ALS Research Center
• Collaborators: Muscular Dystrophy Association
• Investigators: Study Director: Robert G Miller, MD, California Pacific Medical Center

Publications and helpful links

General 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. Erratum In: Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16404-7.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: November 12, 2008
• First Submitted That Met QC Criteria: November 12, 2008
• First Posted (Estimate): November 13, 2008

Study Record Updates

• Last Update Posted (Actual): October 30, 2020
• Last Update Submitted That Met QC Criteria: October 24, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; Lithium; Lou Gehrig's Disease; Lithium Carbonate
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antimanic Agents; Lithium Carbonate
• Other Study ID Numbers: 28.013