Multiple Sclerosis
Conditions
Keywords
multiple sclerosis
Brief summary
Participants (n=20) will be identified at routine care visits performed at the Rochester Multiple Sclerosis Center. Eligible participants will have MS by McDonald Criteria,7 and will have a modified Ashworth spasticity rating8 of two or higher in at least one lower extremity muscle group. Participants will be seen at screening, one, and three months, and will be evaluated using the modified Ashworth scale,8 pendulum test,9 toe tapping test,10 manual muscle testing,11 timed 25 foot walk,12 and Multiple Sclerosis Functional Composite.13 The type and severity of any adverse events will be recorded using standard definitions. Participants will be instructed to call between visits to inform the investigators regarding any adverse events they experience. Follow-up will continue until all adverse events resolve or stabilize.
Detailed description
This is a randomized, placebo controlled, double-blind, parallel group trial of memantine in patients with MS and spasticity. Participants will be identified at routine care visits at the Rochester Multiple Sclerosis Center. After obtaining informed consent, patients will undergo screening, which will include a physical/neurologic exam and an assessment of the Expanded Disability Status Scale, spasticity, and functional abilities. Eligible patients will return for a baseline evaluation, will initiate their randomly assigned study medication, and will return after one and three months for re-evaluation. The type and severity of any adverse events will be recorded using standard definitions. Participants will be instructed to call between visits to inform the investigators regarding any adverse events they experience. Follow-up will continue until all adverse events resolve or stabilize.
Interventions
DRUGplacebo
matched tablets bid
DRUGmemantine
10 mg bid
Sponsors
Forest Laboratories
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Multiple sclerosis by McDonald Criteria. 2. Spasticity. A minimum score of two on the Ashworth spasticity scale in at least one lower extremity muscle group and a total score of at least four in the lower extremity muscles tested. 3. Age 18-70. 4. Normal renal function (estimated CrCl \> 50 ml/min). 5. Women of childbearing potential (i.e., those not postmenopausal or surgically sterile) may participate provided that they are using adequate birth control methods (including barrier methods, IUD, and oral contraceptives) for the duration of the study. 6. Willing and able to perform all procedures related to the clinical trial and to provide informed consent.
Exclusion criteria
1. Evidence of clinically significant thyroid, gastrointestinal, cardiovascular, hepatic, renal, hematologic, respiratory, neoplastic, endocrine (including diabetes mellitus), neurologic (other than MS), or other medical or psychiatric disorder at screening. 2. Women must not be pregnant or lactating. Serum or urine pregnancy tests will be required prior to randomization for women of childbearing potential unless the last menstrual period started less than 28 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Ashworth Spasticity Scale Score Between Baseline and 12 Weeks | Baseline and 12 weeks | spasticity scale score: the most common used tool to measure the degree of spasticity of the lower extremities. Score: Degree of Muscle Tone 0: no increase in tone 1. slight increase in tone 1+: slight increase in tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the range of motion. 2. more marked increase in muscle tone through most of the range of movement, but affected part(s) easily moved. 3. considerable increase in muscle tone, passive movement difficult. 4. affected part(s) rigid in flexion or extension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in the Multiple Sclerosis Spacticy Scale (MSSS-88) Between Baseline and 12 Weeks | baseline, 12 weeks | Multiple Sclerosis Spacticy Scale (MSSS-88) is a patient reported questionnaire rating scale to quantify the perspectives of the impact of spasticity on people with multiple sclerosis. Scoring: Individual items are scored on a 4 point Likert scale: 1 (Not bothered at all), 2 (a little bothered), 3 (moderately bothered), 4 (extremely bothered).This questionnaire asks how bothered you have been by your spasticity in the past two weeks. By spasticity we mean muscle stiffness and spasms.The MSSS-88 is a reliable and valid, patient-based, interval-level measure of the impact of spasticity in multiple sclerosis. Scores were summed, without weighting or standardization, to generate ordinal-level total scores just as any other Likert-type scale. Missing responses to items can be replaced with the mean score of the items completed (person-specific item mean score) provided that 50% or more of the items in a scale have been completed. The range is 8-32 and higher scores mean poorer outcome. |
| Change in Multiple Sclerosis Functional Composite (MSFC) Score Between Baseline and Week 12 | Baseline, Week 12 | 9-Hole Peg Test (9-HPT) is a quantitative measure of upper extremity function. Timed 25-Foot Walk (T 25 FW) is a quantitative measure of lower extremity function. The patient is instructed to walk 25 feet as quickly as possible, but safely. Paced Auditory Serial Addition Test-3 seconds (PASAT-3) is a measure of cognitive function that assesses auditory information processing speed and flexibility, as well as calculation ability. The MSFC is based on the concept that scores for these 3 dimensions-arm, leg, and cognitive function are combined to create a single score that can be used to detect change over time in a group of MS patients. This is done by creating Z-scores for each component of the MSFC. Implicit in this approach is the idea that patients who deteriorate or improve on all 3 component measures will have an overall larger change than patients who change on only 1 of the 3 measures. The MSFC score was transformed to z-scores, with higher scores indicating better outcome. |
Countries
United States
Participant flow
Recruitment details
Recruitment for the trial began in June 2006 and ended in June 2008. The last subject formally completed the trial in September 2008
Participants by arm
| Arm | Count |
|---|---|
| Memantine Memantine 10 mg bid | 11 |
| Placebo Placebo arm | 10 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Memantine | 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 | 10 Participants | 11 Participants | 21 Participants |
| Age, Continuous | 52.1 years STANDARD_DEVIATION 12.2 | 52.9 years STANDARD_DEVIATION 7.5 | 52.5 years STANDARD_DEVIATION 9.8 |
| Region of Enrollment United States | 10 participants | 11 participants | 21 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 5 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 |
Outcome results
Primary
Difference in Ashworth Spasticity Scale Score Between Baseline and 12 Weeks
spasticity scale score: the most common used tool to measure the degree of spasticity of the lower extremities. Score: Degree of Muscle Tone 0: no increase in tone 1. slight increase in tone 1+: slight increase in tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the range of motion. 2. more marked increase in muscle tone through most of the range of movement, but affected part(s) easily moved. 3. considerable increase in muscle tone, passive movement difficult. 4. affected part(s) rigid in flexion or extension.
Time frame: Baseline and 12 weeks
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Difference in Ashworth Spasticity Scale Score Between Baseline and 12 Weeks | -1.55 units on a scale | Standard Deviation 2.81 |
| Placebo | Difference in Ashworth Spasticity Scale Score Between Baseline and 12 Weeks | -1.00 units on a scale | Standard Deviation 2.67 |
Secondary
Change in Multiple Sclerosis Functional Composite (MSFC) Score Between Baseline and Week 12
9-Hole Peg Test (9-HPT) is a quantitative measure of upper extremity function. Timed 25-Foot Walk (T 25 FW) is a quantitative measure of lower extremity function. The patient is instructed to walk 25 feet as quickly as possible, but safely. Paced Auditory Serial Addition Test-3 seconds (PASAT-3) is a measure of cognitive function that assesses auditory information processing speed and flexibility, as well as calculation ability. The MSFC is based on the concept that scores for these 3 dimensions-arm, leg, and cognitive function are combined to create a single score that can be used to detect change over time in a group of MS patients. This is done by creating Z-scores for each component of the MSFC. Implicit in this approach is the idea that patients who deteriorate or improve on all 3 component measures will have an overall larger change than patients who change on only 1 of the 3 measures. The MSFC score was transformed to z-scores, with higher scores indicating better outcome.
Time frame: Baseline, Week 12
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Multiple Sclerosis Functional Composite (MSFC) Score Between Baseline and Week 12 | 0.02 Z score | Standard Deviation 0.26 |
| Placebo | Change in Multiple Sclerosis Functional Composite (MSFC) Score Between Baseline and Week 12 | -0.04 Z score | Standard Deviation 0.2 |
Secondary
Difference in the Multiple Sclerosis Spacticy Scale (MSSS-88) Between Baseline and 12 Weeks
Multiple Sclerosis Spacticy Scale (MSSS-88) is a patient reported questionnaire rating scale to quantify the perspectives of the impact of spasticity on people with multiple sclerosis. Scoring: Individual items are scored on a 4 point Likert scale: 1 (Not bothered at all), 2 (a little bothered), 3 (moderately bothered), 4 (extremely bothered).This questionnaire asks how bothered you have been by your spasticity in the past two weeks. By spasticity we mean muscle stiffness and spasms.The MSSS-88 is a reliable and valid, patient-based, interval-level measure of the impact of spasticity in multiple sclerosis. Scores were summed, without weighting or standardization, to generate ordinal-level total scores just as any other Likert-type scale. Missing responses to items can be replaced with the mean score of the items completed (person-specific item mean score) provided that 50% or more of the items in a scale have been completed. The range is 8-32 and higher scores mean poorer outcome.
Time frame: baseline, 12 weeks
Population: per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Difference in the Multiple Sclerosis Spacticy Scale (MSSS-88) Between Baseline and 12 Weeks | -5.55 units on a scale | Standard Deviation 7.89 |
| Placebo | Difference in the Multiple Sclerosis Spacticy Scale (MSSS-88) Between Baseline and 12 Weeks | -3.33 units on a scale | Standard Deviation 7.07 |