A Pilot Study of Lithium in Progressive Multiple Sclerosis

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

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).

Official Title
-----------------
A Pilot Trial of Lithium in Progressive Multiple Sclerosis

Conditions
-----------------
Multiple Sclerosis

Intervention / Treatment
-----------------
* Drug: Lithium Carbonate


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each study participant agreed to a two-year enrollment commitment. Each subject was asked to take lithium for one year and to be observed for one year. Randomization was used to determine the sequence of lithium vs. observation (year 1 or year 2).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lithium<br>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<br>* Lithium carbonate is dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time.<br>* Other names: Standard care (observation);|
| No Intervention: Observation<br>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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Multiple sclerosis, Lithium