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

• ClinicalTrials.gov Identifier: NCT00790582
• Recruitment Status: Completed
• First Posted: November 13, 2008
• Results First Posted: October 30, 2020
• Last Update Posted: October 30, 2020
• Sponsor: Forbes Norris MDA/ALS Research Center
• Collaborator: Muscular Dystrophy Association
• Information provided by (Responsible Party): Dr. Robert Miller, Forbes Norris MDA/ALS Research Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: lithium carbonate	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 109 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center Controlled Screening Trial of Safety and Efficacy of Lithium Carbonate in Subjects With Amyotrophic Lateral Sclerosis (ALS)
• Study Start Date: May 2008
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: March 2010

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised) [ Time Frame: Baseline, Month 1,3,4.5,6,7.5,9,10.5,12,13 ]
   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)

Secondary Outcome Measures :

1. Vital Capacity [ Time Frame: Screen, Baseline, Month 1,3,6,9,12 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic

Scottsdale, Arizona, United States, 85259

United States, California

UCLA Neuromuscular Research Center

Los Angeles, California, United States, 90095

UC Irvine MDA/ALS & Neuromuscular Center

Orange, California, United States, 92868

California Pacific Medical Center

San Francisco, California, United States, 94115

United States, Kansas

Kansas University Medical Center

Kansas City, Kansas, United States, 66160

United States, Missouri

Washington University Department of Neurology

Saint Louis, Missouri, United States, 63110

United States, Oregon

Providence ALS Clinic

Portland, Oregon, United States, 97213

United States, Pennsylvania

University of Pennsylvania Neurological Institute

Philadelphia, Pennsylvania, United States, 19107

United States, Texas

Methodist Neurological Institute

Houston, Texas, United States, 77030

United States, Utah

University of Utah Clinical Neurosciences Center

Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

Forbes Norris MDA/ALS Research Center

Muscular Dystrophy Association

Investigators

• Study Director: Robert G Miller, MD; California Pacific Medical Center

More Information

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.

• Responsible Party: Dr. Robert Miller, Director, Forbes Norris MDA/ALS Research Center
• ClinicalTrials.gov Identifier: NCT00790582
• Other Study ID Numbers: 28.013
• First Posted: November 13, 2008
• Results First Posted: October 30, 2020
• Last Update Posted: October 30, 2020
• Last Verified: October 2020

Keywords provided by Dr. Robert Miller, Forbes Norris MDA/ALS Research Center:

ALS; Amyotrophic Lateral Sclerosis; Lou Gehrig's Disease; Lithium; Lithium Carbonate

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Lithium Carbonate; Antidepressive Agents; Psychotropic Drugs; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antimanic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs