Trial Outcomes & Findings for Methylphenidate for the Treatment of Gait Impairment in Parkinson's Disease (NCT NCT00526630)

Last Updated: 2015-04-22

Results Overview

Gait stride length is the distance between two consecutive steps in the "on" state. This will be measured by the GAITRite System, which is an electronic walkway utilized to measure the temporal (timing) and spatial (two dimension geometric position) parameters of its pressure activated sensors.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

23 participants

Primary outcome timeframe

Week 12 and 27

Results posted on

2015-04-22

Participant Flow

Twenty-three subjects with PD and moderate gait impairment were enrolled for this 6-month placebo-controlled, double-blind study.

Participant milestones

Participant milestones
Measure	MPD Then Placebo First group treated with MPD then placebo	Placebo Then MPD First group treated with placebo then MPD
First Intervention Period - 12 Weeks STARTED	12	11
First Intervention Period - 12 Weeks COMPLETED	12	8
First Intervention Period - 12 Weeks NOT COMPLETED	0	3
Second Intervention Period - 12 Weeks STARTED	12	8
Second Intervention Period - 12 Weeks COMPLETED	10	7
Second Intervention Period - 12 Weeks NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	MPD Then Placebo First group treated with MPD then placebo	Placebo Then MPD First group treated with placebo then MPD
First Intervention Period - 12 Weeks Withdrawn	0	3
Second Intervention Period - 12 Weeks Withdrawn	2	1

Baseline Characteristics

Methylphenidate for the Treatment of Gait Impairment in Parkinson's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=23 Participants Participants were randomized to receive both MPD and placebo.
Age, Continuous	67.6 years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12 and 27

Outcome measures

Outcome measures
Measure	1. MPD n=20 Participants Randomized to receive active Methylphenidate first. At cross-over, participants will receive placebo.	2. Placebo n=23 Participants Randomized to receive placebo first. At cross-over, participants will receive the active Methylphenidate.	Baseline n=23 Participants Baseline gait composite scores
The Primary Outcome Measure Was Change in a Gait Stride Length Between Groups at 12 and 27 Weeks.	107.66 centimeters Standard Deviation 26.03	112.29 centimeters Standard Deviation 21.85	103.35 centimeters Standard Deviation 24.24

PRIMARY outcome

Timeframe: Week 12 and 27

Gait velocity is a measure of distance over time in the "on" state. This will be measured by the GAITRite System, which is an electronic walkway utilized to measure the temporal (timing) and spatial (two dimension geometric position) parameters of its pressure activated sensors.

Outcome measures

Outcome measures
Measure	1. MPD n=20 Participants Randomized to receive active Methylphenidate first. At cross-over, participants will receive placebo.	2. Placebo n=23 Participants Randomized to receive placebo first. At cross-over, participants will receive the active Methylphenidate.	Baseline n=23 Participants Baseline gait composite scores
The Primary Outcome Measure Was Change in Gait Velocity Between Groups at 12 and 27 Weeks.	96.96 centimeters/second Standard Deviation 22.38	99.24 centimeters/second Standard Deviation 15.16	95.76 centimeters/second Standard Deviation 25.38

SECONDARY outcome

Timeframe: At week 12 and 27

Patients will have a mild to severe gait disturbance with score \>1 on the motor subscale of the Unified Parkinson's disease rating scale (UPDRS) but without need for a continuous ambulatory aid such as walker or wheelchair (Hoehn \& Yahr 2-3). The highest score possible for the UPDRS is 108 which indicates severe motor impairment. The lowest score for the UPDRS is 0 which indicates no motor impairment.

Outcome measures

Outcome measures
Measure	1. MPD n=20 Participants Randomized to receive active Methylphenidate first. At cross-over, participants will receive placebo.	2. Placebo n=23 Participants Randomized to receive placebo first. At cross-over, participants will receive the active Methylphenidate.	Baseline n=23 Participants Baseline gait composite scores
The Unified Parkinson Disease Rating Scale (UPDRS) Between Groups at 12 and 27 Weeks	21.18 units on a scale Standard Deviation 12.73	20.33 units on a scale Standard Deviation 10.48	18.39 units on a scale Standard Deviation 8.21

SECONDARY outcome

Timeframe: Week 12 and 27

Freezing and shuffling are measures of ambulatory impairment.

Outcome measures

Outcome measures
Measure	1. MPD n=20 Participants Randomized to receive active Methylphenidate first. At cross-over, participants will receive placebo.	2. Placebo n=23 Participants Randomized to receive placebo first. At cross-over, participants will receive the active Methylphenidate.	Baseline n=23 Participants Baseline gait composite scores
Duration of Freezing and Shuffling Episodes Between Groups at 12 and 27 Weeks. Shuffling	7.67 hours Standard Deviation 5.02	6.15 hours Standard Deviation 4.05	9.1 hours Standard Deviation 3.7
Duration of Freezing and Shuffling Episodes Between Groups at 12 and 27 Weeks. Freezing	3.07 hours Standard Deviation 2.99	3.25 hours Standard Deviation 3.02	5.4 hours Standard Deviation 4.11

SECONDARY outcome

Timeframe: Week 12 and 27

FOGQ is a questionnaire that quantifies severity of gait and falls. It contains 16 items with a 0-4 severity scale for each, for a range of 0 (normal) to 64 (most severe impairment).

Outcome measures

Outcome measures
Measure	1. MPD n=20 Participants Randomized to receive active Methylphenidate first. At cross-over, participants will receive placebo.	2. Placebo n=23 Participants Randomized to receive placebo first. At cross-over, participants will receive the active Methylphenidate.	Baseline n=23 Participants Baseline gait composite scores
Freezing of Gait Questionnaire (FOGQ) Scores Between Groups at 12 and 27 Weeks.	12.31 units on a scale Standard Deviation 2.73	12.56 units on a scale Standard Deviation 4.11	12.71 units on a scale Standard Deviation 3.87

SECONDARY outcome

Timeframe: Week 12 and 27

MADRS is a questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60

Outcome measures

Outcome measures
Measure	1. MPD n=20 Participants Randomized to receive active Methylphenidate first. At cross-over, participants will receive placebo.	2. Placebo n=23 Participants Randomized to receive placebo first. At cross-over, participants will receive the active Methylphenidate.	Baseline n=23 Participants Baseline gait composite scores
Montgomery-Åsberg Depression Rating Scale (MADRS) Between Groups at 12 and 27 Weeks.	5.79 units on a scale Standard Deviation 5.24	6.71 units on a scale Standard Deviation 6.2	9.44 units on a scale Standard Deviation 5.93

SECONDARY outcome

Timeframe: Week 12 and 27

The Epworth Sleepiness Scale (ESS) is a scale intended to measure daytime sleepiness that is measured by use of a very short questionnaire. The questionnaire asks the subject to rate his or her probability of falling asleep on a scale of increasing probability from 0 to 3 for eight different situations that most people engage in during their daily lives, though not necessarily every day. The scores for the eight questions are added together to obtain a single number. A number in the 0-9 range is considered to be normal while a number in the 10-24 range indicates excessive daytime sleepiness. Higher scores imply worse sleepiness.

Outcome measures

Outcome measures
Measure	1. MPD n=20 Participants Randomized to receive active Methylphenidate first. At cross-over, participants will receive placebo.	2. Placebo n=23 Participants Randomized to receive placebo first. At cross-over, participants will receive the active Methylphenidate.	Baseline n=23 Participants Baseline gait composite scores
The Epworth Sleepiness Scale (ESS) Between Groups at 12 and 27 Weeks	11.05 units on a scale Standard Deviation 4.55	10.71 units on a scale Standard Deviation 3.7	11.24 units on a scale Standard Deviation 3.53

SECONDARY outcome

Timeframe: Week 12 and 27

The EQ-5D comprises five questions on mobility, self care, pain, usual activities, and psychological status with three possible answers for each item (1=no problem, 2=moderate problem, 3=severe problem; see appendix). A summary index with a maximum score of 1 can be derived from these five dimensions by conversion with a table of scores. The range is from 0 to 100, with 100 indicating the best health status.

Outcome measures

Outcome measures
Measure	1. MPD n=20 Participants Randomized to receive active Methylphenidate first. At cross-over, participants will receive placebo.	2. Placebo n=23 Participants Randomized to receive placebo first. At cross-over, participants will receive the active Methylphenidate.	Baseline n=23 Participants Baseline gait composite scores
The 5-item EuroQoL (EQ-5D) Quality of Life Generic Instrument Between Groups at 12 and 27 Weeks.	65 units on a scale Standard Deviation 25.7	63.94 units on a scale Standard Deviation 20.71	68.67 units on a scale Standard Deviation 13.56

Adverse Events

1. MPD

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

2. Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Alberto Espay, MD

University of Cincinnati

Phone: 513-403-4600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	1. MPD n=20 participants at risk Randomized to receive active Methylphenidate first. At cross-over, participants will receive placebo. Methylphenidate (MPD): 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.	2. Placebo n=23 participants at risk Randomized to receive placebo first. At cross-over, participants will receive the active Methylphenidate. Placebo: Participants will be given placebo instead of active MPD.
Psychiatric disorders irritability	25.0% 5/20 • Number of events 5 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	0.00% 0/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Renal and urinary disorders Loss of bladder control	5.0% 1/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	0.00% 0/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Eye disorders Double vision	5.0% 1/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	0.00% 0/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders Bad nightmares, transient	5.0% 1/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	0.00% 0/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders Less dyskinesia	5.0% 1/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	4.3% 1/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders More dyskinesia	15.0% 3/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	4.3% 1/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders Sleep improved	10.0% 2/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	4.3% 1/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders Sleep deteriorated	10.0% 2/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	0.00% 0/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders No strength or energy	25.0% 5/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	4.3% 1/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders Stiffness, soreness, cramps	10.0% 2/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	8.7% 2/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders Visual hallucinations	10.0% 2/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	4.3% 1/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
General disorders Crying	5.0% 1/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	0.00% 0/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Gastrointestinal disorders Suppressed appetite	10.0% 2/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	4.3% 1/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders Lightheadedness	5.0% 1/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	0.00% 0/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders Increased wakefulness	5.0% 1/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	0.00% 0/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders Decreased soreness	5.0% 1/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	0.00% 0/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Psychiatric disorders Anxiety	10.0% 2/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	4.3% 1/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
Nervous system disorders Confusion, forgetfulness	0.00% 0/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	17.4% 4/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.
General disorders Flushing	0.00% 0/20 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.	4.3% 1/23 • Adverse event data was captured during the course of the study either by phone interview or at the study visit.