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Completed

NCT Number: NCT01896700

Methylphenidate to Improve Balance and Walking in MS

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.

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Key information

Age range

20 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Portland VA Medical Center

Portland, Oregon, 97239, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Methylphenidate

Drug

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

Other names: Ritalin

Placebo

Drug

Escalating matched dose of placebo

Primary outcomes

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

    Time frame: 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 outcomes

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

    Time frame: 6 weeks

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

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Oregon Health and Science University

Other

Collaborators

  • Portland VA Medical Center

Registry information

Important dates

Study start
2013
Primary completion
2016
Study completion
2016
First posted
Jul 11, 2013
Registry last updated
Apr 5, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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