Methylphenidate to Improve Balance and Walking in MS

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Methylphenidate

Placebo

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Multiple sclerosis, postural balance, walking

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 20-65
Able to walk at least 100m without an aide or with unilateral assistance
Poor static balance, specifically prolonged APR latencies (≥ 1 standard deviation (SD) > mean for healthy people in this age range), OR
Reduced balance-related activity (ABC scores ≤ 85%)
Walking difficulties, specifically T25FW > 6 seconds, OR reduced self perceived walking (MSWS-12 scores ≥ 50/60)

Exclusion Criteria:

Currently taking methylphenidate, modafinil, or armodafinil.(any within the last 2 weeks)
Cause(s) of imbalance other than MS
Systolic pressure consistently greater than 150 mm Hg or diastolic pressure consistently greater than 90 mm Hg
Contraindications to methylphenidate (Anxiety, tension, agitation, thyrotoxicosis, tachyarrhythmias, severe angina pectoris or glaucoma, hypersensitivity to methylphenidate, motor tics or a family history or diagnosis of Tourette's syndrome, seizures, severe or poorly controlled hypertension, treatment with monoamine oxidase inhibitors currently or within the last 14 days, current use of guanethidine, pressors, coumarin anticoagulants, anticonvulsants, phenylbutazone, or tricyclic antidepressants, history of drug abuse or alcoholism)
Pregnancy or breastfeeding

Sites / Locations

Portland VA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Methylphenidate

Placebo

Arm Description

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

Placebo pill, bid for 6 weeks

Outcomes

Primary Outcome Measures

Change From Baseline in Timed Up and Go (TUG) Test Time at 6 Weeks

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.

Secondary Outcome Measures

Change From Baseline in Automatic Postural Response (APR) Latency at 6 Weeks

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

Change From Baseline in Timed 25 Foot Walk (T25FW) at 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.

Change From Baseline in Pittsburgh Sleep Quality Assessment Questionnaire Score at 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.

Change From Baseline in Modified Fatigue Index Scale Score at 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.

Change From Baseline in Vestibular-Ocular Reflex (VOR) Gain at 6 Weeks

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.

Change From Baseline in Vestibular Ocular Reflex (VOR) Asymmetry (Percentage Asymmetric) at 6 Weeks

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.

Change From Baseline in Vestibular Ocular Reflex (VOR) Phase (in Degrees) at 6 Weeks

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.

Full Information

NCT ID

NCT01896700

First Posted

July 8, 2013

Last Updated

March 8, 2018

Sponsor

Oregon Health and Science University

Collaborators

Portland VA Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01896700

Brief Title

Methylphenidate to Improve Balance and Walking in MS

Official Title

Methylphenidate to Improve Balance and Walking in MS

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

July 2013 (undefined)

Primary Completion Date

April 2016 (Actual)

Study Completion Date

April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Oregon Health and Science University

Collaborators

Portland VA Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Methylphenidate is an amphetamine-like psychomotor stimulant drug currently approved for the treatment of attention-deficit hyperactivity disorder (ADHD), postural orthostasis tachycardia syndrome and narcolepsy. It is also often prescribed off label to people with MS to improve fatigue. It is proposed that methylphenidate may also improve imbalance and walking deficits in MS by improving concentration and central integration, one of the primary mechanisms thought to underlie imbalance and walking deficits in MS.

Detailed Description

The proposed pilot study will examine the effects of methylphenidate on imbalance and walking in 24 subjects with MS and imbalance. The subjects will be randomly assigned to receive either an escalating does of methylphenidate, 20mg, 40mg or 60mg, divided into two doses each day, or matched placebo for 2 weeks at each dose. If a subject does not tolerate dose escalation they will be instructed to discontinue use of the drug. The maximum safely tolerated dose for each subject will be noted. Changes from baseline in subject's walking speed, balance, vestibular function, cognitive function, and fatigue will be assessed at each dose.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

Keywords

Multiple sclerosis, postural balance, walking

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Methylphenidate

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo pill, bid for 6 weeks

Intervention Type

Drug

Intervention Name(s)

Methylphenidate

Other Intervention Name(s)

Ritalin

Intervention Description

Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Escalating matched dose of placebo

Primary Outcome Measure Information:

Title

Change From Baseline in Timed Up and Go (TUG) Test Time at 6 Weeks

Description

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.

Time Frame

6 weeks

Secondary Outcome Measure Information:

Title

Change From Baseline in Automatic Postural Response (APR) Latency at 6 Weeks

Description

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

Time Frame

6 weeks

Title

Change From Baseline in Timed 25 Foot Walk (T25FW) at 6 Weeks

Description

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

Time Frame

6 weeks

Title

Change From Baseline in Pittsburgh Sleep Quality Assessment Questionnaire Score at 6 Weeks

Description

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.

Time Frame

6 weeks

Title

Change From Baseline in Modified Fatigue Index Scale Score at 6 Weeks

Description

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.

Time Frame

6 weeks

Title

Change From Baseline in Vestibular-Ocular Reflex (VOR) Gain at 6 Weeks

Description

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.

Time Frame

6 weeks

Title

Change From Baseline in Vestibular Ocular Reflex (VOR) Asymmetry (Percentage Asymmetric) at 6 Weeks

Description

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.

Time Frame

6 weeks

Title

Change From Baseline in Vestibular Ocular Reflex (VOR) Phase (in Degrees) at 6 Weeks

Description

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.

Time Frame

6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Age 20-65 Able to walk at least 100m without an aide or with unilateral assistance Poor static balance, specifically prolonged APR latencies (≥ 1 standard deviation (SD) > mean for healthy people in this age range), OR Reduced balance-related activity (ABC scores ≤ 85%) Walking difficulties, specifically T25FW > 6 seconds, OR reduced self perceived walking (MSWS-12 scores ≥ 50/60) Exclusion Criteria: Currently taking methylphenidate, modafinil, or armodafinil.(any within the last 2 weeks) Cause(s) of imbalance other than MS Systolic pressure consistently greater than 150 mm Hg or diastolic pressure consistently greater than 90 mm Hg Contraindications to methylphenidate (Anxiety, tension, agitation, thyrotoxicosis, tachyarrhythmias, severe angina pectoris or glaucoma, hypersensitivity to methylphenidate, motor tics or a family history or diagnosis of Tourette's syndrome, seizures, severe or poorly controlled hypertension, treatment with monoamine oxidase inhibitors currently or within the last 14 days, current use of guanethidine, pressors, coumarin anticoagulants, anticonvulsants, phenylbutazone, or tricyclic antidepressants, history of drug abuse or alcoholism) Pregnancy or breastfeeding

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michelle Cameron, PT, MD

Organizational Affiliation

Portland VA Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Portland VA Medical Center

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Multiple Sclerosis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial