A Pilot Study of Lithium in Progressive Multiple Sclerosis

A Pilot Trial of Lithium in Progressive Multiple Sclerosis

The purpose of this study is to determine whether lithium carbonate is safe, well-tolerated, and effective at treating progressive forms of multiple sclerosis.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Lithium Carbonate

Detailed Description

In progressive multiple sclerosis (MS), patients experience worsening disability through a combination of inflammatory and neuro-degenerative processes. To test whether low-dose lithium carbonate ameliorates disability accumulation in progressive MS, patients with progressive MS were randomly assigned to take lithium in either the first or second year of a two-year trial. The trial was designed as a cross-over study to maximize exposure to lithium to for two reasons: 1) To increase the number of persons with MS exposed to lithium for purposes of assessing safety and tolerance; and 2) To increase the power to detect changes in the primary radiological outcome (change in brain volume) and also in secondary clinical outcomes (disability, mood, fatigue, cognition).

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Birmingham VA Medical Center, Birmingham, AL
    • Birmingham, Alabama, United States, 35233
      • Kirklin Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of a progressive subtype of multiple sclerosis by revised 2005 McDonald Criteria.
• EDSS of 3.0-6.5
• Ages 30-65
• Must be mentally capable of providing informed consent and following study guidelines.

Exclusion Criteria:

• Relapse or steroid treatment within 1 month of trial entry.
• Any current or previous treatment with mitoxantrone, azathioprine, methotrexate, mycophenolate, cyclophosphamide, or any experimental therapy.
• Women who are pregnant, wishing to become pregnant in the coming 30 months, or are breastfeeding.
• Sexually active women unwilling to use reliable contraception (oral contraceptives, condom, IUD).
• Patients with known kidney dysfunction or creatinine >1.4; known cardiac arrhythmia or significant conduction abnormality on EKG; uncontrolled thyroid disease or TSH >20% above the upper limit of normal; uncontrolled psoriasis, HIV, or any other severe medical condition.
• Patients with a history of unstable psychiatric illness or active severe depression.
• Patients with a history of seizure.
• Concurrent use of any of the following medications: Antipsychotics, diuretics, digoxin, or iodide salts.
• Use of non-steroidal anti-inflammatory drugs (NSAIDs) 5 or more days a week.
• Patients with a history of substance abuse in the past year.
• Patients sensitive to gadolinium, or who are unable to undergo the required number of MRI scans.
• Unable to speak or understand sufficient English to consent or complete study procedures.
• Patients unable or unwilling to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lithium; Lithium-treatment phase Lithium Carbonate: Lithium carbonate is dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time.	Drug: Lithium Carbonate; Lithium carbonate is dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time.; Other Names: Standard care (observation)
No Intervention: Observation; During observation subjects continue on their standard of care disease modifying agent (or no agent at all if judged not appropriate by the treating physician).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Change in Brain Parenchymal Fraction	Paired comparison of change in brain parenchymal fraction during Lithium treatment and during observation period	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Relapses	Total number of relapses which occurred during the Li-treatment and observation study phases.	2 years
Change in Expanded Disability Status Scale Score	The Expanded Disability Status Scale (EDSS) is an ordinal scale ranging from 0 to 10 used to assess disability in multiple sclerosis (MS). A score of 0 denotes no neurological impairments and no neurological exam abnormalities, while a score of 10 denotes death due to MS. The EDSS is derived from subscales called Functional System Scales at the lower range of the EDSS, and from ambulatory impairments and overall functional impairment at higher ranges of the scale. The Functional System scores (Vision, Brainstem, Pyramidal, Sensory, Cerebellar, Cognitive, Bladder and Bowel) are used to generate the EDSS based on pre-specified rules that determine the overall EDSS score.	2 years

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: John R Rinker, MD, Birmingham VA Medical Center, Birmingham, AL

Publications and helpful links

General Publications

• Rinker JR 2nd, Meador WR, King P. Randomized feasibility trial to assess tolerance and clinical effects of lithium in progressive multiple sclerosis. Heliyon. 2020 Jul 28;6(7):e04528. doi: 10.1016/j.heliyon.2020.e04528. eCollection 2020 Jul.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 10, 2010
• First Submitted That Met QC Criteria: December 10, 2010
• First Posted (Estimate): December 14, 2010

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Lithium
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; 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: CDA2-003-10S

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No