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

Tracking Information

• First Submitted Date: November 12, 2008
• First Posted Date: November 13, 2008
• Results First Submitted Date: February 3, 2011
• Results First Posted Date: October 30, 2020
• Last Update Posted Date: October 30, 2020
• Study Start Date: May 2008
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 24, 2020)

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)

• Original Primary Outcome Measures (submitted: November 12, 2008): ALSFRS-R [ Time Frame: Baseline, Month 1,3,4.5,6,7.5,9,10.5,12,13 ]

Current Secondary Outcome Measures (submitted: October 24, 2020)

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.

Original Secondary Outcome Measures (submitted: November 12, 2008)

• Vital Capacity [ Time Frame: Screen, Baseline, Month 1,3,6,9,12 ]
• Safety Labs [ Time Frame: Screen, Baseline, Month 1,3,6,12 ]
• Adverse Events [ Time Frame: Month 1,3,6,9,12 ]
• Lithium Level (blood) [ Time Frame: Week 2, Month 1,6,12 and 2 weeks after a dose change ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Multi-Center Controlled Screening Trial of Safety and Efficacy of Lithium Carbonate in Subjects With Amyotrophic Lateral Sclerosis (ALS)
• Official Title: A Multi-Center Controlled Screening Trial of Safety and Efficacy of Lithium Carbonate in Subjects With Amyotrophic Lateral Sclerosis (ALS)
• 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis

Intervention

Drug: lithium carbonate

The dosage of lithium carbonate will be adjusted for each individual. The maximum dose is 450mg/day.

Study Arms

Experimental: lithium carbonate

Intervention: Drug: lithium carbonate

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 24, 2020): 109
• Original Estimated Enrollment (submitted: November 12, 2008): 100
• Actual Study Completion Date: March 2010
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00790582
• Other Study ID Numbers: 28.013
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Dr. Robert Miller, Forbes Norris MDA/ALS Research Center
• Study Sponsor: Forbes Norris MDA/ALS Research Center
• Collaborators: Muscular Dystrophy Association

Investigators

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

• PRS Account: Forbes Norris MDA/ALS Research Center
• Verification Date: October 2020