Clinical trial NCT00526630: Methylphenidate for the Treatment of Gait Impairment in Parkinson's Disease
Official title: Methylphenidate for the Treatment of Gain Impairment in Parkinson's Disease: a Randomized Double-Blind, Placebo-Controlled, Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson's Disease
Gait Impairment
Keywords: freezing
gait
festination
shuffling
balance
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
First posted: 2007-09-10
Enrollment: 23
Sex: ALL
Minimum age (years): 35
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Primary Outcome Measure Was Change in a Gait Stride Length Between Groups at 12 and 27 Weeks.
timeFrame: Week 12 and 27
measure: The Primary Outcome Measure Was Change in Gait Velocity Between Groups at 12 and 27 Weeks.
timeFrame: Week 12 and 27
Secondary outcomes:
measure: The Unified Parkinson Disease Rating Scale (UPDRS) Between Groups at 12 and 27 Weeks
timeFrame: At week 12 and 27
measure: Duration of Freezing and Shuffling Episodes Between Groups at 12 and 27 Weeks.
timeFrame: Week 12 and 27
measure: Freezing of Gait Questionnaire (FOGQ) Scores Between Groups at 12 and 27 Weeks.
timeFrame: Week 12 and 27
measure: Montgomery-Åsberg Depression Rating Scale (MADRS) Between Groups at 12 and 27 Weeks.
timeFrame: Week 12 and 27
measure: The Epworth Sleepiness Scale (ESS) Between Groups at 12 and 27 Weeks
timeFrame: Week 12 and 27
measure: The 5-item EuroQoL (EQ-5D) Quality of Life Generic Instrument Between Groups at 12 and 27 Weeks.
timeFrame: Week 12 and 27
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University Neurology-Movement Disorders Clinic
state: Ohio
Study officials:
affiliation: University of Cincinnati-Neurology
name: Alberto Espay, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Espay AJ, Dwivedi AK, Payne M, Gaines L, Vaughan JE, Maddux BN, Slevin JT, Gartner M, Sahay A, Revilla FJ, Duker AP, Shukla R. Methylphenidate for gait impairment in Parkinson disease: a randomized clinical trial. Neurology. 2011 Apr 5;76(14):1256-62. doi: 10.1212/WNL.0b013e3182143537.