Cannabis for Spasticity in Multiple Sclerosis

A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 3 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; only 25 total subjects had Lido assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 3 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; only 25 total subjects had Lido assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 7 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 26 subjects had Lido assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 7 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 26 subjects had Lido assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The Timed 25 Foot Walk is a quantitative measure of lower extremity function. The patient is instructed to walk on a marked 25-foot course, as quickly and as safely as possible. The patient is allowed to use his/her typical walking aid, if applicable. The task is completed twice and the average time of the two trials was used for this outcome measure. The change was calculated by taking the Week 3 time and subtracting the Week 0 time. A negative result indicates an improvement in walking ability and correlates to a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 22 total subjects had 25 Foot Walk tests performed at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The 9 hold peg test is a quantitative measure of upper extremity (arm and hand function). Patients are instructed to fill an 9 hole peg board with 1 peg at a time and then immediately remove the pegs, 1 at a time. The dominant hand is tested twice and the average time was used for this outcome measure. The change was calculated by taking the Week 3 time and subtracting the Week 0 time. A negative result indicates an improvement in arm and hand function and correlates with a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 26 total subjects had 9 Hole Peg tests (dominant hand) at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The 9 hold peg test is a quantitative measure of upper extremity (arm and hand function). Patients are instructed to fill an 9 hole peg board with 1 peg at a time and then immediately remove the pegs, 1 at a time. The non-dominant hand is tested twice and the average time was used for this outcome measure. The change was calculated by taking the Week 3 time and subtracting the Week 0 time. A negative result indicates an improvement in arm and hand function and correlates with a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 26 total subjects had 9 Hole peg tests (non-dom. hand) at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The AI is a 9-point rating scale used to assess mobility by evaluating the time and degree of assistance required to walk 25 feet. Scores range from 0 (asymptomatic, fully active) to 9 (restricted to wheelchair, unable to transfer self independently). Lower scores represent a better outcome for MS patients. For this study, the AI score was based on the results of the 25 Foot Walk test, also performed at the study visit. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result for this outcome indicates an improvement in ambulation and correlates to a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 27 total subjects had Ambulation Index assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The total EDSS score ranges from 0 to 10, in 0.5 unit increments. A score of 0 is the lowest (normal neurological exam) and 10 is the highest (death due to MS). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 28 total subjects had completed \& scored EDSS assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Bowel and Bladder score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (loss of bowel and bladder function). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 28 total subjects had FS Bowel \& Bladder assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Brainstem score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (inability to swallow or speak). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 28 total subjects had FS Brainstem assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Cerebellar score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (unable to perform coordinated movements due to ataxia). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 27 total subjects had FS Cerebellar assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Cerebral score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (dementia). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome. Fatigue did not contribute to this FS score or the EDSS total score.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 28 total subjects had FS Cerebral assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Pyramidal score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (tetraplegia (grade 0 or 1 in all muscle groups of upper and lower limbs). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 28 total subjects had FS Pyramidal assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Sensory score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (sensation essentially lost below the head). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 28 total subjects had FS Sensory assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Vision score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (grade 5 plus maximal visual acuity of better eye of 20/60 (0.3) or less). Higher values indicate more impaired vision. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in vision and correlates to a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 27 total subjects had FS Vision assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The Modified Ashworth scale measures resistance during passive soft-tissue stretching. Spasticity is graded on a scale of 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). The highest score (flexion or extension), for the lower extremities only, was used for each subject. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates a decrease in spasticity and correlates to a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 28 total subjects had Ashworth assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The Bladder Control Scale is a 4-item scale developed to assess the impact of multiple sclerosis on bladder function. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-22. The scale is set up so that a higher score indicates greater bladder control problems. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in bladder control and correlates to a better outcome. A positive result indicates a decrease in bladder control and correlates to a worse outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE \& withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 27 total subjects completed all Bladder Control scale questions at both the Wk 0 and Wk 3 study visits and were analyzed for this outcome measure.

The Bowel Control Scale is a 5-item scale developed to assess the impact of multiple sclerosis on bowel function. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-26. The scale is set up so that a higher score indicates greater bowel control problems. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in bowel control and correlates to a better outcome. A positive result indicates a decrease in bowel control and correlates to a worse outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE \& withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 26 total subjects completed all Bowel Control scale questions at both the Wk 0 and Wk 3 study visits and were analyzed for this outcome measure.

The Impact of Visual Impairment Scale is a 5-item scale developed to assess the extent to which activities dependent on vision are affected by MS-related visual problems. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-15. The scale is set up so that a higher score indicates greater impact of visual problems on daily activities. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of visual problems on daily activities and correlates to a better outcome. A positive result indicates an increase in the impact of visual problems on daily activities and correlates to a worse outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE \& withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 27 total subjects completed all Impact of Visual Impairment scale questions at both the Wk 0 and Wk 3 study visits and were analyzed for this outcome measure.

The Mental Health Inventory (MHI) is an 18-item scale developed as a measure of overall emotional functioning. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-100. The scale is set up so that a higher score indicates better mental health. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A positive result indicates an improvement in mental health and correlates to a better outcome. A negative result indicates decrease in mental health and correlates to a worse outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through Wk 7; 2 subjects who discontinued early (AE \& withdraw by subject) were active at Wk 3 and were included in the Wk 3 analysis; 14 subjects completed all MHI questions at both the Wk 0 and Wk 3 and were analyzed for this outcome measure. The MHI was added late to the study beginning with subject 22 of 42

The Modified Fatigue Index is a 21-item scale developed to assess the perceived impact of fatigue on daily activities. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-84. The scale is set up so that a higher score indicates a greater impact of fatigue on a patient's daily activities. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of fatigue on daily activities and correlates to a better outcome. A positive result indicates an increase in the impact of fatigue on daily activities and correlates to a worse outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE \& withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 26 total subjects completed all Modified Fatigue Index questions at both the Wk 0 and Wk 3 study visits and were analyzed for this outcome measure.

The Modified Social Support Scale is an 18-item scale developed as a measure of perceived social support. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-100. The scale is set up so that a higher score indicates greater perceived support. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A positive result indicates an improvement in perceived support and correlates to a better outcome. A negative result indicates a decrease in perceived support and correlates to a worse outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE \& withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 26 total subjects completed all Modified Social Support scale questions at both the Wk 0 and Wk 3 study visits and were analyzed for this outcome measure.

The Pain Effects Scale is a 6-item scale developed to assess the effects of pain on behavior and mood. It is a part of the MS Quality of Life Inventory. The scale is measured from 6-30. The scale is set up so that a higher score indicates a greater impact of pain on a patient's mood and behavior. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of pain on mood and behavior and correlates to a better outcome. A positive result indicates an increase in the impact of pain on mood and behavior and correlates to a worse outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE \& withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 28 total subjects completed all Pain Effects scale questions at both the Wk 0 and Wk 3 study visits and were analyzed for this outcome measure.

The Perceived Deficits Scale is a 20-item scale developed to assess the patient's perceived cognitive deficits. It is composed of four 5-item subscales: Attention/Concentration, Retrospective Memory, Prospective Memory, and Planning/Organization. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-80. The scale is set up so that a higher score indicates greater perceived cognitive impairment. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates a decrease in the perception of cognitive impairment. A positive result indicates an increase in the perception of cognitive impairment. Since patient perceptions of cognitive impairment may not correlate with objective measures of cognitive impairment, the results should be interpreted with caution.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE \& withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 27 total subjects completed all Perceived Deficits scale questions at both the Wk 0 and Wk 3 study visits and were analyzed for this outcome measure.

The Sexual Satisfaction Scale is a 4-item scale developed to assess the impact of multiple sclerosis on sexual function and satisfaction. It is a part of the MS Quality of Life Inventory. The scale is measured from 4-24. The scale is set up so that a higher score indicates greater problems with sexual satisfaction. Subjects that answered No to the question, Do you have a relationship with one primary partner, did not complete the scale. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in sexual satisfaction and correlates to a better outcome. A positive result indicates a decrease in sexual satisfaction and correlates to a worse outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE \& withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 19 total subjects completed all Sexual Satisfaction scale questions at both the Wk 0 and Wk 3 study visits and were analyzed for this outcome measure.

The SF-36 is a 36-item scale developed as a generic health status measure. It is a part of the MS Quality of Life Inventory. It can be reported as 2 summary scales - the Physical and Mental components. The scale is measured from 0 -100. The scale is set up so that a higher score indicates better health. The change was calculated by taking the Week 3 score and subtracting the Week 0. A positive result indicates an improvement in mental health status and correlates to a better outcome. A negative result indicates a decline in mental health and correlates to a worse outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE \& withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 21 total subjects completed all SF-36 mental component questions at both the Wk 0 and Wk 3 study visits and were analyzed for this outcome measure.

The SF-36 is a 36-item scale developed as a generic health status measure. It is a part of the MS Quality of Life Inventory. It can be reported as 2 summary scales - the Physical and Mental components. The scale is measured from 0 -100. The scale is set up so that a higher score indicates better health. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A positive result indicates an improvement in health status and correlates to a better outcome. A negative result indicates a decline in health and correlates to a worse outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE \& withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 21 total subjects completed all SF-36 physical component questions at both the Wk 0 and Wk 3 study visits and were analyzed for this outcome measure.

The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability; The test is presented via recording on a CD to control the rate of stimulus presentation. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. The test score is the number of correct sums given (out of a possible 60) in each trial. There are 2 test forms, A and B. The forms were alternated and at least 1 practice test (10 sums) was performed prior to each trial. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in performance and correlates with a better outcome.

Time frame: Week 0, Week 3

Population: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; 29 total subjects had PASAT assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

The Timed 25 Foot Walk is a quantitative measure of lower extremity function. The patient is instructed to walk on a marked 25-foot course, as quickly and as safely as possible. The patient is allowed to use his/her typical walking aid, if applicable. The task is completed twice and the average time of the two trials was used for this outcome measure. The change was calculated by taking the Week 7 time and subtracting the Week 0 time. A negative result indicates an improvement in walking ability and correlates to a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 26 subjects had 25 Foot Walk tests performed at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The 9 hold peg test is a quantitative measure of upper extremity (arm and hand function). Patients are instructed to fill an 9 hole peg board with 1 peg at a time and then immediately remove the pegs, 1 at a time. The dominant hand is tested twice and the average time was used for this outcome measure. The change was calculated by taking the Week 7 time and subtracting the Week 0 time. A negative result indicates an improvement in arm and hand function and correlates with a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects had 9 Hole Peg tests (dominant hand) performed at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The 9 hold peg test is a quantitative measure of upper extremity (arm and hand function). Patients are instructed to fill an 9 hole peg board with 1 peg at a time and then immediately remove the pegs, 1 at a time. The dominant hand is tested twice and the average time was used for this outcome measure. The change was calculated by taking the Week 7 time and subtracting the Week 0 time. A negative result indicates an improvement in arm and hand function and correlates with a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 25 subjects had 9 Hole Peg tests (non-dom. hand) performed at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The AI is a 9-point rating scale used to assess mobility by evaluating the time and degree of assistance required to walk 25 feet. Scores range from 0 (asymptomatic, fully active) to 9 (restricted to wheelchair, unable to transfer self independently). Lower scores represent a better outcome for MS patients. For this study, the AI score was based on the results of the 25 Foot Walk test, also performed at the study visit. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result for this outcome indicates an improvement in ambulation and correlates to a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, all 28 subjects had Ambulation Index assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The total EDSS score ranges from 0 to 10, in 0.5 unit increments. A score of 0 is the lowest (normal neurological exam) and 10 is the highest (death due to MS). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects had completed \& scored EDSS assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Bowel and Bladder score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (loss of bowel and bladder function). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects had FS Bowel \& Bladder assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Brainstem score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (inability to swallow or speak). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects had FS Brainstem assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Cerebellar score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (unable to perform coordinated movements due to ataxia). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects had FS Cerebellar assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Cerebral score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (dementia). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome. Fatigue did not contribute to this FS score or the EDSS total score.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects had FS Cerebral assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Pyramidal score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (tetraplegia (grade 0 or 1 in all muscle groups of upper and lower limbs). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects had FS Pyramidal assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Sensory score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (sensation essentially lost below the head). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects had FS Sensory assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Vision score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (grade 5 plus maximal visual acuity of better eye of 20/60 (0.3) or less). Higher values indicate more impaired vision. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in vision and correlates to a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects had FS Vision assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The Modified Ashworth scale measures resistance during passive soft-tissue stretching. Spasticity is graded on a scale of 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). The highest score (flexion or extension), for the lower extremities only, was used for each subject. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates a decrease in spasticity and correlates to a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects had Ashworth assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The Bladder Control Scale is a 4-item scale developed to assess the impact of multiple sclerosis on bladder function. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-22. The scale is set up so that a higher score indicates greater bladder control problems. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in bladder control and correlates to a better outcome. A positive result indicates a decrease in bladder control and correlates to a worse outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, all 28 subjects completed all Bladder Control scale questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The Bowel Control Scale is a 5-item scale developed to assess the impact of multiple sclerosis on bowel function. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-26. The scale is set up so that a higher score indicates greater bowel control problems. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in bowel control and correlates to a better outcome. A positive result indicates a decrease in bowel control and correlates to a worse outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects completed all Bowel Control scale questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The Impact of Visual Impairment Scale is a 5-item scale developed to assess the extent to which activities dependent on vision are affected by MS-related visual problems. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-15. The scale is set up so that a higher score indicates greater impact of visual problems on daily activities. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of visual problems on daily activities and correlates to a better outcome. A positive result indicates an increase in the impact of visual problems on daily activities and correlates to a worse outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 27 subjects completed all Impact of Visual Impairment scale questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The Mental Health Inventory (MHI) is an 18-item scale developed as a measure of overall emotional functioning. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-100. The scale is set up so that a higher score indicates better mental health. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A positive result indicates an improvement in mental health and correlates to a better outcome. A negative result indicates decrease in mental health and correlates to a worse outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 14 subjects completed all Mental Health Inventory questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure. The Mental Health Inventory was added late to the study beginning with subject 22 of 42

The Modified Fatigue Index is a 21-item scale developed to assess the perceived impact of fatigue on daily activities. It is a part of the MS Quality of Life Inventory. The scale is measured from 0 - 84. The scale is set up so that a higher score indicates a greater impact of fatigue on a patient's daily activities. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of fatigue on daily activities and correlates to a better outcome. A positive result indicates an increase in the impact of fatigue on daily activities and correlates to a worse outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 26 subjects completed all Modified Fatigue Index questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The Modified Social Support Scale is an 18-item scale developed as a measure of perceived social support. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-100. The scale is set up so that a higher score indicates greater perceived support. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A positive result indicates an improvement in perceived support and correlates to a better outcome. A negative result indicates a decrease in perceived support and correlates to a worse outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 26 subjects completed all Modified Social Support scale questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The Pain Effects Scale is a 6-item scale developed to assess the effects of pain on behavior and mood. It is a part of the MS Quality of Life Inventory. The scale is measured from 6-30. The scale is set up so that a higher score indicates a greater impact of pain on a patient's mood and behavior. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of pain on mood and behavior and correlates to a better outcome. A positive result indicates an increase in the impact of pain on mood and behavior and correlates to a worse outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, all 28 subjects completed all Pain Effects scale questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The Perceived Deficits Scale is a 20-item scale developed to assess the patient's perceived cognitive deficits. It is composed of four 5-item subscales: Attention/Concentration, Retrospective Memory, Prospective Memory, and Planning/Organization. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-80. The scale is set up so that a higher score indicates greater perceived cognitive impairment. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates a decrease in the perception of cognitive impairment. A positive result indicates an increase in the perception of cognitive impairment. Since patient perceptions of cognitive impairment may not correlate with objective measures of cognitive impairment, the results should be interpreted with caution.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 26 subjects completed all Perceived Deficits scale questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The Sexual Satisfaction Scale is a 4-item scale developed to assess the impact of multiple sclerosis on sexual function and satisfaction. It is a part of the MS Quality of Life Inventory. The scale is measured from 4-24. The scale is set up so that a higher score indicates greater problems with sexual satisfaction. Subjects that answered No to the question, Do you have a relationship with one primary partner, did not complete the scale. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in sexual satisfaction and correlates to a better outcome. A positive result indicates a decrease in sexual satisfaction and correlates to a worse outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 19 subjects completed all Sexual Satisfaction scale questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The SF-36 is a 36-item scale developed as a generic health status measure. It is a part of the MS Quality of Life Inventory. It can be reported as 2 summary scales - the Physical and Mental components. The scale is measured from 0 -100. The scale is set up so that a higher score indicates better health. The change was calculated by taking the Week 3 score and subtracting the Week 0. A positive result indicates an improvement in mental health status and correlates to a better outcome. A negative result indicates a decline in mental health and correlates to a worse outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 23 subjects completed all SF-36 mental component questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The SF-36 is a 36-item scale developed as a generic health status measure. It is a part of the MS Quality of Life Inventory. It can be reported as 2 summary scales - the Physical and Mental components. The scale is measured from 0 -100. The scale is set up so that a higher score indicates better health. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A positive result indicates an improvement in health status and correlates to a better outcome. A negative result indicates a decline in health and correlates to a worse outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, only 23 subjects completed all SF-36 physical component questions at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.

The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability; The test is presented via recording on a CD to control the rate of stimulus presentation. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. The test score is the number of correct sums given (out of a possible 60) in each trial. There are 2 test forms, A and B. The forms were alternated and at least 1 practice test (10 sums) was performed prior to each trial. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in performance and correlates with a better outcome.

Time frame: Week 0, Week 7

Population: Only 28 subjects completed the study through the Wk 7 visit; Of these 28 subjects, all 28 subjects had PASAT assessments at both the Week 0 and Week 7 study visits and were able to be analyzed for this outcome measure.