Clinical trial NCT01259388: A Pilot Study of Lithium in Progressive Multiple Sclerosis
Official title: A Pilot Trial of Lithium in Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis
Keywords: Multiple sclerosis
Lithium
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2010-12-14
Enrollment: 23
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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).
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Rate of Change in Brain Parenchymal Fraction
timeFrame: 2 years
Secondary outcomes:
measure: Total Relapses
timeFrame: 2 years
measure: Change in Expanded Disability Status Scale Score
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham VA Medical Center, Birmingham, AL
state: Alabama
city: Birmingham
country: United States
facility: Kirklin Clinic
state: Alabama
Study officials:
affiliation: Birmingham VA Medical Center, Birmingham, AL
name: John R Rinker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.