Methylphenidate for the Treatment of Gait Impairment in Parkinson's Disease
Methylphenidate for the Treatment of Gait Impairment in Parkinson's Disease
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.
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.
Inclusion Criteria:

 -  Patients with a definite diagnosis of Parkinson's disease for at least 5 years.

 -  Patients with mild to severe gait disturbance.

 -  Patients on a stable dose of anti-parkinsonian medications that will not be expected
 to require medication adjustments.

 -  Mini-Mental State Examination (MMSE) score of 25 or greater.

 Exclusion Criteria:

 -  Patients with musculoskeletal disorders such as severe arthritis, post knee surgery,
 hip surgery, or any other condition that the investigators determine may impair
 assessment of gait.

 -  Previous treatment with DBS (deep brain stimulation).

 -  Those with history of stroke.

 -  Those with cerebellar, vestibular, or sensory ataxia.

 -  Concurrent use of, or within two weeks from discontinuing, MAO inhibitor drugs
 (selegiline, rasagiline).

 -  Women of childbearing potential.