ECTRIMS Online Library

Results of a pilot trial of lithium in progressive multiple sclerosis
Author(s): ,
J.R Rinker
Affiliations:
Neurology, University of Alabama at Birmingham;Neurology, Birmingham VA Medical Center
,
W Meador
Affiliations:
Neurology, University of Alabama at Birmingham
,
V Sung
Affiliations:
Neurology, University of Alabama at Birmingham;Neurology, Birmingham VA Medical Center
,
A Nicholas
Affiliations:
Neurology, University of Alabama at Birmingham;Neurology, Birmingham VA Medical Center
G Cutter
Affiliations:
Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United States
ECTRIMS Online Library. Rinker J. 09/16/16; 145965; P1282
Dr. John R. Rinker
Dr. John R. Rinker
Contributions
Abstract

Abstract: P1282

Type: Poster

Abstract Category: Therapy - disease modifying - Treatment of progressive MS

Background: Progression in multiple sclerosis (MS) denotes the insidious accumulation of disability over time, driven by inflammatory demyelination and neurodegeneration. Current immune modulating drugs have shown little effect in progressive MS, so novel pharmacologic approaches to treat progression are needed.

Lithium carbonate (Li) is a pharmacologically active cation which distributes widely throughout the brain and has been shown to impart neuroprotective effects in several models of degenerative diseases. Li also ameliorates inflammatory demyelination in murine models of MS. Presented here are the results of a pilot trial designed to test the safety, feasibility, and efficacy of Li in a progressive MS cohort.

Methods: Subjects consented to a 2-year, open-label crossover trial of adjunct Li vs. standard care. Subjects were randomly assigned to take up to 300 mg Li daily in year 1 or 2. Annual clinical, radiological, and laboratory assessments were used to assess the primary outcomes of safety/tolerability and change in brain parenchymal fraction (BPF). Secondary outcome measures included relapse rates, changes in expanded disability status scale (EDSS) and MS functional composite, and scales of depression, fatigue, and quality of life.

Results: Of 23 consented subjects, 17 completed the 2-year study. Two of 6 subjects discontinued due to Li-intolerance (worsening gait), while 4 discontinued for personal or medical reasons unrelated to the study. Mean age at enrollment was 51 ± 7.8 years, and mean duration of disease was 14 ± 10.5 years. Median baseline EDSS was 4.

The most commonly reported side effects included increased thirst (n=11), polyuria (n=9), and fatigue (n=7). Myoclonic jerks or tremor affected 5 subjects but did not limit treatment. Two subjects experienced asymptomatic increases in thyroid stimulating hormone which resolved upon Li cessation. Relapse rates and change in EDSS did not significantly differ between on- and off-Li time periods.

Twenty three of 34 MRI pairs were available for change in BPF comparison at the time of publication. During Li treatment, BPF increased by a mean of 0.560 ± 0.379%, compared to 0.139 ± 0.304% during standard care (p=0.399).

Conclusions: In a progressive MS cohort, low-dose Li was well-tolerated and preliminary analysis does not rule out a benefit on brain volume compared to standard care. Future studies designed around efficacy should better clarify Li"s role as a treatment for progressive MS.

Disclosure: Funding for the trial was provided through the Department of Veterans Affairs, CDA2-003-10S.

Dr. Rinker reports no conflicts of interest related to the conduct of the study.

Dr. Meador reports no conflicts of interest related to the conduct of the study.

Dr. Sung reports no conflicts of interest related to the conduct of the study.

Dr. Nicholas reports no conflicts of interest related to the conduct of the study.

Dr. Cutter reports no conflicts of interest related to the conduct of the study.



Abstract: P1282

Type: Poster

Abstract Category: Therapy - disease modifying - Treatment of progressive MS

Background: Progression in multiple sclerosis (MS) denotes the insidious accumulation of disability over time, driven by inflammatory demyelination and neurodegeneration. Current immune modulating drugs have shown little effect in progressive MS, so novel pharmacologic approaches to treat progression are needed.

Lithium carbonate (Li) is a pharmacologically active cation which distributes widely throughout the brain and has been shown to impart neuroprotective effects in several models of degenerative diseases. Li also ameliorates inflammatory demyelination in murine models of MS. Presented here are the results of a pilot trial designed to test the safety, feasibility, and efficacy of Li in a progressive MS cohort.

Methods: Subjects consented to a 2-year, open-label crossover trial of adjunct Li vs. standard care. Subjects were randomly assigned to take up to 300 mg Li daily in year 1 or 2. Annual clinical, radiological, and laboratory assessments were used to assess the primary outcomes of safety/tolerability and change in brain parenchymal fraction (BPF). Secondary outcome measures included relapse rates, changes in expanded disability status scale (EDSS) and MS functional composite, and scales of depression, fatigue, and quality of life.

Results: Of 23 consented subjects, 17 completed the 2-year study. Two of 6 subjects discontinued due to Li-intolerance (worsening gait), while 4 discontinued for personal or medical reasons unrelated to the study. Mean age at enrollment was 51 ± 7.8 years, and mean duration of disease was 14 ± 10.5 years. Median baseline EDSS was 4.

The most commonly reported side effects included increased thirst (n=11), polyuria (n=9), and fatigue (n=7). Myoclonic jerks or tremor affected 5 subjects but did not limit treatment. Two subjects experienced asymptomatic increases in thyroid stimulating hormone which resolved upon Li cessation. Relapse rates and change in EDSS did not significantly differ between on- and off-Li time periods.

Twenty three of 34 MRI pairs were available for change in BPF comparison at the time of publication. During Li treatment, BPF increased by a mean of 0.560 ± 0.379%, compared to 0.139 ± 0.304% during standard care (p=0.399).

Conclusions: In a progressive MS cohort, low-dose Li was well-tolerated and preliminary analysis does not rule out a benefit on brain volume compared to standard care. Future studies designed around efficacy should better clarify Li"s role as a treatment for progressive MS.

Disclosure: Funding for the trial was provided through the Department of Veterans Affairs, CDA2-003-10S.

Dr. Rinker reports no conflicts of interest related to the conduct of the study.

Dr. Meador reports no conflicts of interest related to the conduct of the study.

Dr. Sung reports no conflicts of interest related to the conduct of the study.

Dr. Nicholas reports no conflicts of interest related to the conduct of the study.

Dr. Cutter reports no conflicts of interest related to the conduct of the study.



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