Trial Outcomes & Findings for A Pilot Study of Lithium in Progressive Multiple Sclerosis (NCT NCT01259388)
NCT ID: NCT01259388
Last Updated: 2019-09-10
Results Overview
Paired comparison of change in brain parenchymal fraction during Lithium treatment and during observation period
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
23 participants
Primary outcome timeframe
2 years
Results posted on
2019-09-10
Participant Flow
Participant milestones
| Measure |
Lithium First (One Year), Then Observation (One Year)
Subjects randomized to this group took lithium carbonate dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time, followed by a year of observation (standard care). No washout period occurred between the treatment periods.
|
Observation First (One Year), Then Lithium (One Year)
Subjects randomized to this group were observed for a year of observation (standard care), followed by a year of lithium carbonate dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time. No washout period occurred between the treatment periods.
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
12
|
|
Overall Study
COMPLETED
|
6
|
11
|
|
Overall Study
NOT COMPLETED
|
5
|
1
|
Reasons for withdrawal
| Measure |
Lithium First (One Year), Then Observation (One Year)
Subjects randomized to this group took lithium carbonate dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time, followed by a year of observation (standard care). No washout period occurred between the treatment periods.
|
Observation First (One Year), Then Lithium (One Year)
Subjects randomized to this group were observed for a year of observation (standard care), followed by a year of lithium carbonate dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time. No washout period occurred between the treatment periods.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
A Pilot Study of Lithium in Progressive Multiple Sclerosis
Baseline characteristics by cohort
| Measure |
Lithium Then Observation
n=11 Participants
Lithium carbonate was dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time.
During observation subjects continued on their standard of care disease modifying agent (or no agent at all if judged not appropriate by the treating physician).
|
Observation Then Lithium
n=12 Participants
During observation subjects continued on their standard of care disease modifying agent (or no agent at all if judged not appropriate by the treating physician).
Lithium carbonate was dosed at 150 or 300 mg daily, as tolerated by study subjects, for one year's time.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55.4 years
STANDARD_DEVIATION 4.6 • n=5 Participants
|
47.1 years
STANDARD_DEVIATION 8.1 • n=7 Participants
|
51.0 years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: 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.
Paired comparison of change in brain parenchymal fraction during Lithium treatment and during observation period
Outcome measures
| Measure |
Lithium
n=17 Participants
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.
|
Observation
n=17 Participants
During observation subjects continued on their standard of care disease modifying agent (or no agent at all if judged not appropriate by the treating physician).
|
|---|---|---|
|
Rate of Change in Brain Parenchymal Fraction
|
0.107 percentage of change in brain volume
Standard Error 0.38
|
-0.355 percentage of change in brain volume
Standard Error 0.22
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: 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.
Total number of relapses which occurred during the Li-treatment and observation study phases.
Outcome measures
| Measure |
Lithium
n=17 Participants
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.
|
Observation
n=17 Participants
During observation subjects continued on their standard of care disease modifying agent (or no agent at all if judged not appropriate by the treating physician).
|
|---|---|---|
|
Total Relapses
|
2 relapses
|
5 relapses
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: 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.
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.
Outcome measures
| Measure |
Lithium
n=17 Participants
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.
|
Observation
n=17 Participants
During observation subjects continued on their standard of care disease modifying agent (or no agent at all if judged not appropriate by the treating physician).
|
|---|---|---|
|
Change in Expanded Disability Status Scale Score
|
0 Units on a scale
Interval 0.0 to 0.0
|
0.5 Units on a scale
Interval 0.0 to 1.0
|
Adverse Events
Lithium
Serious events: 1 serious events
Other events: 22 other events
Deaths: 0 deaths
Observation
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lithium
n=23 participants at risk
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.
|
Observation
n=18 participants at risk
During observation subjects continued on their standard of care disease modifying agent (or no agent at all if judged not appropriate by the treating physician).
|
|---|---|---|
|
Renal and urinary disorders
Hospitalization to place suprapubic catheter
|
0.00%
0/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
5.6%
1/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma
|
4.3%
1/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
Other adverse events
| Measure |
Lithium
n=23 participants at risk
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.
|
Observation
n=18 participants at risk
During observation subjects continued on their standard of care disease modifying agent (or no agent at all if judged not appropriate by the treating physician).
|
|---|---|---|
|
General disorders
Excess thirst
|
78.3%
18/23 • Number of events 112 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
General disorders
Fatigue
|
65.2%
15/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
Renal and urinary disorders
Polyuria
|
65.2%
15/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
General disorders
Weight gain
|
56.5%
13/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
General disorders
Weight loss
|
43.5%
10/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
Nervous system disorders
Tremor
|
43.5%
10/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
Nervous system disorders
Cognitive change
|
30.4%
7/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
26.1%
6/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
Nervous system disorders
Gait impairment
|
21.7%
5/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
Skin and subcutaneous tissue disorders
Acne
|
13.0%
3/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
Endocrine disorders
Increased TSH
|
8.7%
2/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
Gastrointestinal disorders
Nausea
|
4.3%
1/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
|
Nervous system disorders
Unusual dreams
|
4.3%
1/23 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
0.00%
0/18 • 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.
Serious and unexpected adverse events were collected for both lithium and observation years. However, since this was an open-label study, subjects were only asked about medication side effects during the lithium-treatment portion of the study. For this reason the Observation period does not list non-serious adverse events.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place