Multiple SclerosisPhase 1/2NCT01259388

A Pilot Study of Lithium in Progressive Multiple Sclerosis

A Phase 1/2 study testing Lithium Carbonate in people with Multiple Sclerosis, run by VA Office of Research and Development at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 30 to 65 years
Conditions the study is for: Multiple Sclerosis
What is being tested?: Lithium Carbonate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 23 participants
Where: 2 sitesUnited States
Study dates: May 2011to Dec 2015
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 30 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 13Show fewer

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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Birmingham VA Medical Center, Birmingham, AL
Birmingham, Alabama, 35233
Kirklin Clinic
Birmingham, Alabama, 35233

Other trials in United States

About this study

Official title: 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.

Read the 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).

Conditions: Multiple Sclerosis
Being tested: Lithium Carbonate
Keywords: Multiple sclerosis, Lithium
Medical subject headings: Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Lithium CarbonateDrug
Also called Standard care (observation)
Lithium carbonate is dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time.

Study groups in NCT01259388
Study group	Role	What they receive
Lithium	Experimental	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. Receives: Drug: Lithium Carbonate
Observation	No intervention	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 being measured

The primary outcome is the main question the study is designed to answer.

Rate of Change in Brain Parenchymal Fraction
Paired comparison of change in brain parenchymal fraction during Lithium treatment and during observation period
Measured: 2 years

Secondary outcomes (2)

Total Relapses
Total number of relapses which occurred during the Li-treatment and observation study phases.
Measured: 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.
Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2011Dec 2015

First posted14 Dec 2010 (estimated)
Study startMay 2011
Primary completionAug 2015
Study completionDec 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Multiple SclerosisStudies of the same condition, open and under way.
More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
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 blind
Who is masked: Outcomes assessor
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01259388
Sponsor's protocol ID: CDA2-003-10S
Status last verified: Aug 2019
First submitted: 10 Dec 2010
Last updated: 10 Sep 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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.
PubMed 32760832

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Multiple Sclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Trial of Lithium in Progressive Multiple Sclerosis
ClinicalTrials.gov ID: NCT01259388
Acronym / sponsor ID: CDA2-003-10S
Conditions: Multiple Sclerosis
Keywords: Multiple sclerosis, Lithium
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: VA Office of Research and DevelopmentUS federal agency
Study start: May 2011
Primary completion: Aug 2015 (actual)
Study completion: Dec 2015 (actual)
First posted: 14 Dec 2010 (estimated)
Results: Posted 10 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Single blind (outcomes assessor)
Number of arms: 2
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).

Arm	Type	Receives
Lithium	Experimental	Drug: Lithium CarbonateLithium-treatment phase Lithium Carbonate: Lithium carbonate is dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time.
Observation	No intervention	–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).

Who may qualify

Ages: 30 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (13 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Lithium CarbonateAlso: Standard care (observation)Lithium carbonate is dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time.	Drug	Lithium

Primary outcome

Rate of Change in Brain Parenchymal Fraction
Time frame: 2 years
Paired comparison of change in brain parenchymal fraction during Lithium treatment and during observation period

2 secondary outcomes

Total Relapses
Time frame: 2 years
Change in Expanded Disability Status Scale Score
Time frame: 2 years

Results and safety

Results posted to the registry on 10 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lithium First (One Year), Then Observation (One Year)	11	6
Observation First (One Year), Then Lithium (One Year)	12	11

Primary outcome: Rate of Change in Brain Parenchymal Fraction

Time frame: 2 years. Mean (Standard Error). Unit: percentage of change in brain volume

Measure	Lithium n = 17	Observation n = 17
Value	0.107 (0.38)	-0.355 (0.22)

Lithium vs Observation: p = 0.346, t-test, 2 sided

Population analysed: Due to this being a crossover study design, each participant's data was evaluated for each phase of the trial (Li treatment and observation). Only subjects who completed both years (and thus both phases) of the study were included.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected over the entire period of study involvement (2 years). For each subject, 1 year was observation and the other year subjects were taking the study medication, lithium carbonate.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lithium	1 of 23 (4.3%)	22 of 23 (95.7%)	Not reported
Observation	1 of 18 (5.6%)	0 of 18 (0%)	Not reported

Limitations and caveats (from the sponsor): This was a pilot study and thus by design was not powered to detect therapeutic differences. The primary purpose of the study was feasibility with the specified outcomes intended to generate preliminary data for subsequent research.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32760832Rinker 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

John R Rinker, MD principal investigator

Birmingham VA Medical Center, Birmingham, AL

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lithium Carbonate in people with Multiple Sclerosis, run by VA Office of Research and Development at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Change in Brain Parenchymal Fraction (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01259388, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019.