Multiple Sclerosis, Chronic Progressive
Conditions
Keywords
Multiple Sclerosis, Multiple sclerosis, chronic progressive, Neuroprotective agents, Magnetic resonance imaging, Optical coherence tomography, Gait, Thioctic acid, Alpha-lipoic acid
Brief summary
The purpose of the study is to determine if lipoic acid can protect the brain and slow disability in secondary progressive multiple sclerosis.
Detailed description
There are no approved medications that are neuroprotective or able to slow disability accumulation in secondary progressive multiple sclerosis (SPMS). This two-year study will determine if daily oral intake of lipoic acid, a natural supplement, will prove superior to placebo in reducing injury to the brain and reducing disability progression in SPMS. Neuroprotection will be measured by the extent of brain volume loss seen on MRI, and disability will be measured by neurological status and quality of life.
Interventions
DRUGlipoic acid
1200 mg taken by mouth daily starting on day one of the study and ending on the last day of study participation.
DRUGPlacebo
The placebo comparator will be taken by mouth daily starting on day one of the study and ending on the last day of study participation
Sponsors
Oregon Health and Science University
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of SPMS * Age 40-70 years * Able to understand English and able to give informed consent
Exclusion criteria
* Unable to undergo MRI testing * For ambulatory subjects only, a self-reported medical or neurological condition other than MS that is a cause of progressive or fluctuating problems that affect walking(e.g. worsening neuropathy, uncontrolled lower extremity arthritis, uncontrolled heart or lung disease) * For ambulatory subjects only, fixed and/or stable conditions of less than 1 years duration that affect walking (e.g. joint replacement, lumbar stenosis, alcoholism, stroke, etc.) * Pregnant or breast-feeding. * Current major disease or disorder other than MS (such as cancer, kidney, heart or lung disease, post-traumatic stress disorder) that may interfere with study procedures * Natalizumab, mitoxantrone, azathioprine taken in the last 12 months * Other immunosuppressants or chemotherapies taken in the last 12 months * Scheduled (every 3 months or more frequently) IV steroids used in the last 12 months * IV or oral steroids taken in the past 60 days. * Lipoic acid taken in the past 60 days. * Subject has insulin-dependent diabetes or is not controlled on oral diabetes medications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Brain Atrophy by MRI | % change brain volume from baseline to year 2 |
Secondary
| Measure | Time frame |
|---|---|
| Disability Measures: Mobility | Change in Timed 25 Foot Walk from baseline to year 2 |
| Safety Measure: Adverse Events | adverse events recorded from baseline to year 2 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lipoic Acid 28 subjects receive oral lipoic acid 1200mg daily
lipoic acid: 1200 mg taken by mouth daily starting on day one of the study and ending on the last day of study participation. | 28 |
| Placebo 28 subjects receive placebo daily
Placebo: The placebo comparator will be taken by mouth daily starting on day one of the study and ending on the last day of study participation | 26 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Lipoic Acid | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 28 Participants | 54 Participants |
| Age, Continuous | 59.7 years STANDARD_DEVIATION 6.1 | 57.9 years STANDARD_DEVIATION 6.7 | 58.7 years STANDARD_DEVIATION 6.4 |
| Gender Female | 16 Participants | 16 Participants | 32 Participants |
| Gender Male | 10 Participants | 12 Participants | 22 Participants |
| Region of Enrollment United States | 26 participants | 28 participants | 54 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 28 | 22 / 26 |
| serious Total, serious adverse events | 9 / 28 | 6 / 26 |
Outcome results
Primary
Brain Atrophy by MRI
Time frame: % change brain volume from baseline to year 2
Population: 22 subjects in the lipoic acid group and 24 in the placebo group completed the MRI outcome. Two outliers in the lipoic acid group were not included in analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lipoic Acid | Brain Atrophy by MRI | -0.4 whole brain percent volume change | Standard Deviation 0.7 |
| Placebo | Brain Atrophy by MRI | -1.3 whole brain percent volume change | Standard Deviation 1.1 |
Secondary
Disability Measures: Mobility
Time frame: Change in Timed 25 Foot Walk from baseline to year 2
Population: Outliers were removed and intention-to-treat analysis was performed on data from 21 participants in the lipoic acid group and 17 in the placebo group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lipoic Acid | Disability Measures: Mobility | -1.0 seconds | Standard Deviation 2.8 |
| Placebo | Disability Measures: Mobility | 0.1 seconds | Standard Deviation 2 |
Secondary
Safety Measure: Adverse Events
Time frame: adverse events recorded from baseline to year 2
Population: Intention-to-treat analysis was performed on 27 participants in the lipoic acid group and 24 in the placebo group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lipoic Acid | Safety Measure: Adverse Events | Total number adverse events | 81 occurences |
| Lipoic Acid | Safety Measure: Adverse Events | Total number serious adverse events | 9 occurences |
| Placebo | Safety Measure: Adverse Events | Total number adverse events | 69 occurences |
| Placebo | Safety Measure: Adverse Events | Total number serious adverse events | 6 occurences |