Methylphenidate for the Treatment of Gait Impairment in Parkinson's Disease
Condition: Parkinson's Disease; Gait Impairment
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this research study is to examine whether Methylphenidate (MPD) can result in
      improvement of gait (walking) in a population of Parkinson's Disease (PD) patients whose main
      disability is freezing of gait. MPD (Ritalin®) is a drug which can excite or stimulate
      certain systems of the body that control motor function. This drug is FDA approved for the
      treatment of attention hyperactivity disorder, a condition unrelated to PD.

      The researchers hypothesize that daily treatment with a tolerable daily oral dose of MPD will
      improve gait velocity, stride length, cadence, and decrease freezing of gait, 3 months from
      treatment initiation in patients with moderately advanced PD, whose gait impairment is an
      important source of disability despite optimized antiparkinsonian treatment.
    

Detailed description: 
      There are a total of six clinic visits involved in this study. All study-related assessments
      will take place first during the practically defined off period, that is, in the morning
      after at least 12 hours from the last dose of any antiparkinsonian medication, followed by a
      repeat assessment once the "on" state is clearly identified by the patient and examiner
      (approximately 30 to 60 minutes after taking your Parkinson's medication). This "practically
      defined off period" state is considered the desired state on which to report motor changes
      for any currently available or experimental intervention in PD. Patients will be off his or
      her Parkinson's medication for no more than 14 hours for each of the assessments. Studying
      patients in the off-period is the most widely used manner in which the value of new therapies
      can be fully measured.

      During the first visit, patients will be "randomized" into one of the study groups described
      below. Neither the participant nor the researcher conducting this study will choose what
      group he or she will be in.

      Participants will receive either placebo or a dose of 1 mg/kg of Methylphenidate capsules
      divided into three doses (at 8 am, 12 noon, and 4 pm). An increase in medication over a four
      week period will be used until a target dosage is reached, which may range from 5 to 8 10-mg
      capsules per day.

      A measure of balance will be taken during both patient's "off" and "on" motor states during
      each of the study visits. Patients will be asked to stand on a force plate (a piece of
      equipment that measures your balance and is located in the floor) for thirty seconds in a
      total of four conditions. The four sessions will be carried out as follows: (1) with eyes
      open while standing on firm surface, (2) with eyes closed while standing on firm surface, (3)
      with eyes open while standing on foam surface, and (4) with eyes closed while standing on
      foam surface. These sessions will be in random order and will be repeated up to 4 times.

      During all the study visits, the physician will ask patients to perform some physical tests
      during which the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr
      (H&Y) will be used to assess the severity of the patient's Parkinson's disease. Each
      assessment will take place during both patient's "off" and "on" motor states. Instruments
      that will also be used are the self-administered Freezing of Gait Questionnaire (FOGQ), to
      evaluate walking difficulties, and the Gait-Falls diary, to document all indoor and outdoor
      freezing, tripping, and falls. To assess changes in mood, patients will also complete the
      following instruments: the Montgomery-Asberg Depression scale (MADRS), the 15-item Geriatric
      Depression Scale (GDS-15) and the 20-item Zung Self-Rating Depression scale (Zung). To assess
      quality of life and activities of daily living, patients will complete the EQ-5D Health
      Questionnaire. Finally, patients will be asked to complete the Epworth Sleepiness Scale (ESS)
      to document any changes in sleep patterns.

      After the first visit, patients will begin a four week increase in medication in order to
      reach a target dose. At the fourth visit, patients will receive the opposite treatment of
      what was received the first time and another four-week increase in medication will take
      place. If Methylphenidate was given at the first visit, patients will receive placebo on the
      third visit and vice versa. There will be a three week period where patients will not take
      the study medication (either Methylphenidate or placebo), between the third and fourth visit.
      At all study visits, during both patient's "off" and "on" motor states, patients will have
      balance testing. The physician will evaluate the severity of patient's disease using the
      UPDRS and the H&Y. Patients will be asked to complete the FOGQ and the Gait-Falls diary.
    

Intervention name(s): Methylphenidate (MPD); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Participants will be given 1 mg/kg of MPD divided in three doses (at 8 am, 12 noon, and 4 pm). A four-week titration period will be used, using 0.25-mg/kg increments per week until achieving the weight-adjusted target dosage, which may range from five to eight 10-mg tablets per day. The maximum daily dose will be 80 mg/day.; Participants will be given placebo instead of active MPD.
Other intervention name(s): Ritalin
Intervention MeSH terms: Methylphenidate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: freezing; gait; festination; shuffling; balance