search
Back to results

A Pilot Study of Lithium in Progressive Multiple Sclerosis

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lithium Carbonate
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Multiple sclerosis, Lithium

Eligibility Criteria

30 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Birmingham VA Medical Center, Birmingham, AL
  • Kirklin Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Lithium

Observation

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

Rate of Change in Brain Parenchymal Fraction
Paired comparison of change in brain parenchymal fraction during Lithium treatment and during observation period

Secondary Outcome Measures

Total Relapses
Total number of relapses which occurred during the Li-treatment and observation study phases.
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.

Full Information

First Posted
December 10, 2010
Last Updated
August 21, 2019
Sponsor
VA Office of Research and Development
search

1. Study Identification

Unique Protocol Identification Number
NCT01259388
Brief Title
A Pilot Study of Lithium in Progressive Multiple Sclerosis
Official Title
A Pilot Trial of Lithium in Progressive Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Multiple sclerosis, Lithium

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
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
Outcomes Assessor
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lithium
Arm Type
Experimental
Arm Description
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.
Arm Title
Observation
Arm Type
No Intervention
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Lithium Carbonate
Other Intervention Name(s)
Standard care (observation)
Intervention Description
Lithium carbonate is dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time.
Primary Outcome Measure Information:
Title
Rate of Change in Brain Parenchymal Fraction
Description
Paired comparison of change in brain parenchymal fraction during Lithium treatment and during observation period
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Total Relapses
Description
Total number of relapses which occurred during the Li-treatment and observation study phases.
Time Frame
2 years
Title
Change in Expanded Disability Status Scale Score
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John R Rinker, MD
Organizational Affiliation
Birmingham VA Medical Center, Birmingham, AL
Official's Role
Principal Investigator
Facility Information:
Facility Name
Birmingham VA Medical Center, Birmingham, AL
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Kirklin Clinic
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32760832
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.
Results Reference
derived

Learn more about this trial

A Pilot Study of Lithium in Progressive Multiple Sclerosis

We'll reach out to this number within 24 hrs