Trial Outcomes & Findings for Methylphenidate to Improve Balance and Walking in MS (NCT NCT01896700)

Last Updated: 2018-04-05

Results Overview

The primary outcome of this study will be the difference between mean change in TUG time between methylphenidate and placebo treated subjects at 6 weeks. Mean changes will be compared for active and placebo treated subjects using Bayesian analysis.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

24 participants

Primary outcome timeframe

6 weeks

Results posted on

2018-04-05

Participant Flow

24 people with MS and imbalance from the MS clinics in the Portland, OR metropolitan area were enrolled into this study between September 2013 and March 2016 .

Participant milestones

Participant milestones
Measure	Methylphenidate Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Overall Study STARTED	12	12
Overall Study COMPLETED	8	6
Overall Study NOT COMPLETED	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Methylphenidate Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Overall Study Adverse Event	4	5
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Methylphenidate to Improve Balance and Walking in MS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methylphenidate n=12 Participants Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo n=12 Participants Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo	Total n=24 Participants Total of all reporting groups
Age, Continuous	46.4 years STANDARD_DEVIATION 7.9 • n=5 Participants	51.7 years STANDARD_DEVIATION 8.7 • n=7 Participants	49.0 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	5 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	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	11 Participants n=7 Participants	21 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	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks

Outcome measures

Outcome measures
Measure	Methylphenidate n=8 Participants Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo n=6 Participants Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Change From Baseline in Timed Up and Go (TUG) Test Time at 6 Weeks	-0.7 change in seconds from basline Standard Error 0.5	-1.3 change in seconds from basline Standard Error 0.2

SECONDARY outcome

Timeframe: 6 weeks

Population: Population discrepancy: One participant in the intervention group and two participants in the placebo group contributed unusable APR data; due to their balance deficits, the machine could not get an accurate reading for this test. One participant in the intervention group declined this test. These four participants were not included in analysis.

Mean changes in APR latency at 6 weeks will be compared for active and placebo treated subjects using Bayesian analysis.

Outcome measures

Outcome measures
Measure	Methylphenidate n=6 Participants Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo n=4 Participants Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Change From Baseline in Automatic Postural Response (APR) Latency at 6 Weeks	-9.2 change in milliseconds from baseline Standard Error 2.2	-5.3 change in milliseconds from baseline Standard Error 1.8

SECONDARY outcome

Timeframe: 6 weeks

Mean changes in Timed 25 Foot Walk (T25FW) at 6 weeks will be compared for active and placebo treated subjects using Bayesian analysis.

Outcome measures

Outcome measures
Measure	Methylphenidate n=8 Participants Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo n=6 Participants Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Change From Baseline in Timed 25 Foot Walk (T25FW) at 6 Weeks	-0.3 change in seconds from baseline Standard Error 0.7	-0.6 change in seconds from baseline Standard Error 0.2

SECONDARY outcome

Timeframe: 6 weeks

Mean changes in the score attained on the Pittsburgh Sleep Quality Assessment Questionnaire at 6 weeks will be compared for active and placebo treated subjects using Bayesian analysis. Scale ranges from 0-21 points, with higher numbers indicating poorer sleep quality.

Outcome measures

Outcome measures
Measure	Methylphenidate n=8 Participants Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo n=6 Participants Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Change From Baseline in Pittsburgh Sleep Quality Assessment Questionnaire Score at 6 Weeks	0.3 change in score from baseline Standard Error 0.9	-0.3 change in score from baseline Standard Error 0.7

SECONDARY outcome

Timeframe: 6 weeks

Mean changes in the score attached on the Modified Fatigue Index Scale at 6 weeks will be compared for active and placebo treated subjects using Bayesian analysis. Scale ranges from 0-84 points, with higher scores indicating greater fatigue.

Outcome measures

Outcome measures
Measure	Methylphenidate n=8 Participants Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo n=6 Participants Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Change From Baseline in Modified Fatigue Index Scale Score at 6 Weeks	-3.8 change in score from baseline Standard Error 3.5	-9.8 change in score from baseline Standard Error 4.4

SECONDARY outcome

Timeframe: 6 weeks

Population: Explanation of population discrepancy: One participant in the active group declined this test, so was not analyzed.

The most common rotary chair testing is a battery of subtests, each at a specific rate (Hz) of chair rotation from side to side. The participant is secured in the chair in total darkness while the eyes are monitored by infrared cameras. We completed tests from 0.04 to 0.64 Hz to assess the vestibular system across a range of head movements. The chair and participant's head move together while the cameras track the velocity of the eyes; eye velocity reveals how the vestibular system responds to head velocity. VOR gain is the ratio of average chair (i.e. head) velocity to average eye velocity, and is represented on a unitless scale from 0 to 1. VOR gain close to 1 indicates that eye velocity is nearly equal and opposite to head velocity. While there are normative ranges for VOR gain, we are most interested in is change in mean gain (6-week tests minus baseline tests) for the active and placebo groups.

Outcome measures

Outcome measures
Measure	Methylphenidate n=7 Participants Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo n=6 Participants Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Change From Baseline in Vestibular-Ocular Reflex (VOR) Gain at 6 Weeks VOR Gain at 0.08 Hz	-0.0061 ratio Standard Deviation 0.0759	-0.283 ratio Standard Deviation 0.0340
Change From Baseline in Vestibular-Ocular Reflex (VOR) Gain at 6 Weeks VOR Gain at 0.04 Hz	-0.0107 ratio Standard Deviation 0.0868	-0.0229 ratio Standard Deviation 0.0521
Change From Baseline in Vestibular-Ocular Reflex (VOR) Gain at 6 Weeks VOR Gain at 0.16 Hz	-0.0151 ratio Standard Deviation 0.0949	0.0871 ratio Standard Deviation 0.0702
Change From Baseline in Vestibular-Ocular Reflex (VOR) Gain at 6 Weeks VOR Gain at 0.32 Hz	-0.0422 ratio Standard Deviation 0.1154	0.0322 ratio Standard Deviation 0.0680
Change From Baseline in Vestibular-Ocular Reflex (VOR) Gain at 6 Weeks VOR Gain at 0.64 Hz	0.0221 ratio Standard Deviation 0.0894	0.0151 ratio Standard Deviation 0.0614

SECONDARY outcome

Timeframe: 6 weeks

Population: Explanation of population discrepancy: One participant in the active group declined this test, so was not analyzed.

Mean changes in VOR asymmetry, which is a measure of the strength of the eye responses in one direction compared with the other as measured by rotary chair testing at 6 weeks, will be compared for active and placebo treated subjects using t-tests, or other appropriate statistical analyses. A range of frequencies was tested from 0.04 Hz to 0.64 Hz, as is standard for rotary chair testing. The range of frequencies (i.e. chair speeds) assesses the vestibular system across a range of head movements. This helps to identify abnormality, which may manifest at different frequencies of movement. The measurement outcomes for rotary chair testing are gain, phase and asymmetry of the eye movements.

Outcome measures

Outcome measures
Measure	Methylphenidate n=7 Participants Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo n=6 Participants Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Change From Baseline in Vestibular Ocular Reflex (VOR) Asymmetry (Percentage Asymmetric) at 6 Weeks VOR Asymmetry at 0.04 Hz	0.9927 change in % of asymmetry from baseline Standard Deviation 5.6664	-1.7291 change in % of asymmetry from baseline Standard Deviation 2.3367
Change From Baseline in Vestibular Ocular Reflex (VOR) Asymmetry (Percentage Asymmetric) at 6 Weeks VOR Asymmetry at 0.08 Hz	-0.0572 change in % of asymmetry from baseline Standard Deviation 5.6678	-6.5209 change in % of asymmetry from baseline Standard Deviation 1.9883
Change From Baseline in Vestibular Ocular Reflex (VOR) Asymmetry (Percentage Asymmetric) at 6 Weeks VOR Asymmetry at 0.16 Hz	2.5833 change in % of asymmetry from baseline Standard Deviation 3.1565	-5.2852 change in % of asymmetry from baseline Standard Deviation 4.9239
Change From Baseline in Vestibular Ocular Reflex (VOR) Asymmetry (Percentage Asymmetric) at 6 Weeks VOR Asymmetry at 0.32 Hz	1.9157 change in % of asymmetry from baseline Standard Deviation 5.1153	-4.1203 change in % of asymmetry from baseline Standard Deviation 5.4695
Change From Baseline in Vestibular Ocular Reflex (VOR) Asymmetry (Percentage Asymmetric) at 6 Weeks VOR Asymmetry at 0.64 Hz	0.3104 change in % of asymmetry from baseline Standard Deviation 4.0893	-1.5111 change in % of asymmetry from baseline Standard Deviation 3.7015

SECONDARY outcome

Timeframe: 6 weeks

Population: Explanation of population discrepancy: One participant in the active group declined this test, so was not analyzed.

Mean changes in VOR phase, which is a measure of the timing (in degrees) of the eye movements relative to the chair movement, as measured by rotary chair testing at 6 weeks, will be compared for active and placebo treated subjects using t-tests, or other appropriate statistical analyses. A range of frequencies was tested from 0.04 Hz to 0.64 Hz, as is standard for rotary chair testing. The range of frequencies (i.e. chair speeds) assesses the vestibular system across a range of head movements. This helps to identify abnormality, which may manifest at different frequencies of movement. The measurement outcomes for rotary chair testing are gain, phase and asymmetry of the eye movements.

Outcome measures

Outcome measures
Measure	Methylphenidate n=7 Participants Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo n=6 Participants Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Change From Baseline in Vestibular Ocular Reflex (VOR) Phase (in Degrees) at 6 Weeks VOR Phase at 0.04 Hz	2.2790 change in degrees from baseline Standard Deviation 5.2622	1.9535 change in degrees from baseline Standard Deviation 4.2274
Change From Baseline in Vestibular Ocular Reflex (VOR) Phase (in Degrees) at 6 Weeks VOR Phase at 0.08 Hz	1.8914 change in degrees from baseline Standard Deviation 4.2548	-1.4716 change in degrees from baseline Standard Deviation 2.5754
Change From Baseline in Vestibular Ocular Reflex (VOR) Phase (in Degrees) at 6 Weeks VOR Phase at 0.16 Hz	0.9449 change in degrees from baseline Standard Deviation 2.2400	-0.3342 change in degrees from baseline Standard Deviation 3.6845
Change From Baseline in Vestibular Ocular Reflex (VOR) Phase (in Degrees) at 6 Weeks VOR Phase at 0.32 Hz	-1.3564 change in degrees from baseline Standard Deviation 7.0617	0.5981 change in degrees from baseline Standard Deviation 3.6808
Change From Baseline in Vestibular Ocular Reflex (VOR) Phase (in Degrees) at 6 Weeks VOR Phase at 0.64 Hz	-2.7082 change in degrees from baseline Standard Deviation 3.6010	0.2833 change in degrees from baseline Standard Deviation 1.7800

Adverse Events

Methylphenidate

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Andrea Hildebrand

Portland VA Health Care System

Phone: 503-220-8262

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Methylphenidate n=12 participants at risk Intervention: An escalating dose of methylphenidate taken by mouth: 20mg for 2 weeks, 40mg for 2 weeks, 60mg for 2 weeks. All doses divided twice/day. Other name: Ritalin Methylphenidate: Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each	Placebo n=12 participants at risk Placebo pill, bid for 6 weeks Placebo: Escalating matched dose of placebo
Vascular disorders Elevated blood pressure	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	25.0% 3/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Cardiac disorders Elevated heart rate	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Chest pain/tightness	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Headache	16.7% 2/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	16.7% 2/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Insomnia	50.0% 6/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	33.3% 4/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Nightmares	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Fatigue	16.7% 2/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Gastrointestinal disorders Stomach ache/indigestion	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Gastrointestinal disorders Constipation	25.0% 3/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	16.7% 2/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Gastrointestinal disorders Nausea	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Abdominal cramping	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Metabolism and nutrition disorders Reduced appetite	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Agitation	16.7% 2/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Irritation	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Emotional detachment	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Musculoskeletal and connective tissue disorders Spasms of limbs	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Musculoskeletal and connective tissue disorders Back pain	25.0% 3/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Musculoskeletal and connective tissue disorders Muscle weakness	16.7% 2/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Musculoskeletal and connective tissue disorders Muscle pain	25.0% 3/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Skin and subcutaneous tissue disorders Itchiness	25.0% 3/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Skin and subcutaneous tissue disorders Rash	16.7% 2/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Tingling sensation	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Increased body heat	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Respiratory, thoracic and mediastinal disorders Coughing/sneezing/respiratory effects	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	33.3% 4/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Dry mouth	16.7% 2/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Dizziness	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	16.7% 2/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Respiratory, thoracic and mediastinal disorders Shortness of breath	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Infections and infestations Throat/ear infection	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
General disorders Reduced balance	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Injury, poisoning and procedural complications Fall	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	25.0% 3/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Injury, poisoning and procedural complications Car accident	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Nervous system disorders MS relapse	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.
Social circumstances Family emergency	0.00% 0/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.	8.3% 1/12 • Each participant was monitored for adverse events during the 6 weeks of their participation in the study.