The Effect of Methylphenidate on Non-motor Symptoms and Postural Control in Parkinson's Disease.

This study has been terminated.
(Inadequate enrolment, protocol too challenging for participants, lack of observable benefit after analysis of 6 patients.)
Sponsor:
Collaborators:
Fonds de la Recherche en Santé du Québec
Quebec Memory and Motor Skills Disorders Research Center
Information provided by (Responsible Party):
Jaime McDonald, Laval University
ClinicalTrials.gov Identifier:
NCT01244269
First received: November 18, 2010
Last updated: October 19, 2012
Last verified: October 2012
  Purpose

This project aims to determine if methylphenidate can improve deficits in attention and symptoms of orthostatic hypotension, two common non-motor symptoms, in patients with Parkinson's Disease. This project also seeks to evaluate the effect of methylphenidate on postural control in these patients, a debilitating motor symptom that places patients at an increased risk of falling. This study will build on existing data to support a new indication for the use of methylphenidate in Parkinson's Disease. Using standard and objective evaluations, this study will quantify the effect of methylphenidate at two doses on attention levels, orthostatic hypotension, and measures of postural control. Phase I of the study will compare methylphenidate 10mg three times daily to placebo and Phase II of the study, for those tolerating the lower dose in Phase I, will compare methylphenidate 20mg three times daily to placebo. By incorporating two different doses, the study also seeks to determine if any improvements are dose-related. Secondary endpoints will include safety assessments (adverse event monitoring and vital signs) performed every 30 minutes following supervised drug administration. Visual analog scales will be presented to each participant before treatment and following the final dose of each treatment to assess changes in fatigue. A secondary task will be added to postural tests to assess the influence of cognitive processes. It is hypothesized that methylphenidate will demonstrate a significant beneficial effect on all outcomes. It is projected that objective improvements will be observed following treatment with methylphenidate at both doses (10 and 20mg three time daily) when compared to placebo. It is further hypothesized that the effects will be dose-related and therefore more profound with higher doses.


Condition Intervention Phase
Parkinson's Disease
Drug: Methylphenidate
Drug: Placebo 10
Drug: Placebo 20
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Two-phase Randomized Controlled Trial of Low and Moderate Dose Methylphenidate for Non-motor and Postural Symptoms in Parkinson's Disease.

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • Conners' Continuous Performance Test-II score [ Time Frame: Baseline, 2 hours following first dose, 2 hours following last dose ] [ Designated as safety issue: No ]
  • Orthostatic drop - blood pressure in mmHg [ Time Frame: Baseline, 2 hours following first dose, 2 hours following last dose ] [ Designated as safety issue: No ]
    Blood pressure will be measured following 5 minutes of rest in a lying position and again 1, 3, and 5 minutes after rising to a standing position. The orthostatic drop will be calculated by subtracting the blood pressures recorded at each time interval(1, 3, and 5 minutes after standing) from the blood pressure recorded in a lying position.

  • Average speed of center of pressure oscillations [ Time Frame: Baseline, 2 hours following first dose, 2 hours following last dose ] [ Designated as safety issue: No ]
    As recorded using dynamic posturography (Sensory Organization Test).

  • Total area of center of pressure oscillations [ Time Frame: Baseline, 2 hours following first dose, 2 hours following last dose ] [ Designated as safety issue: No ]
    As recorded using dynamic posturography (Sensory Organization Test).


Secondary Outcome Measures:
  • Visual analog fatigue scale scores [ Time Frame: Baseline, 2 hours following last dose ] [ Designated as safety issue: No ]
  • Blood pressure (mmHg) [ Time Frame: Baseline, 30, 60, and 90 minutes following first and final dose of study medication ] [ Designated as safety issue: Yes ]
  • Heart rate [ Time Frame: Basesline, 30, 60, and 90 minutes following first and final dose of study medication ] [ Designated as safety issue: Yes ]
  • Number of errors recorded for 'Backward Digit Span' task [ Time Frame: Baseline, 2 hours following first dose, 2 hours following final dose ] [ Designated as safety issue: No ]
    Following administration of the Backward Digit Span assessment of the Wechsler Adult Intelligence Scale to control for individual capacities, each subject will be provided with a string of digits before the onset of 50% of the trials in the postural test. Subjects will be required to memorize the string of digits in reverse and repeat them at the end of the trial. Errors will be quantified as either errors of insertion, deletion, or order.


Enrollment: 6
Study Start Date: December 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methylphenidate 10
Methylphenidate 10mg three times daily for a total of 7 doses.
Drug: Methylphenidate
Methylphenidate 10mg tablets will be overencapsulated in gelatin capsules for blinding. Subjects will take 1 capsule three times daily for a total of 7 doses.
Other Name: Ritalin
Placebo Comparator: Placebo 10
Placebo capsule three times daily for a total of 7 doses.
Drug: Placebo 10
Blind gelatin capsule three times daily for a total of 7 doses.
Experimental: Methylpheindate 20
Methylphenidate 20mg three times daily for a total of 7 doses.
Drug: Methylphenidate
Methylphenidate 20mg three times daily for a total of 7 doses.
Other Name: Ritalin
Placebo Comparator: Placebo 20
Placebo capsule three times daily for a total of 7 doses.
Drug: Placebo 20
Blind gelatin capsule three times daily for a total of 7 doses

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with stages 2-3 Parkinson's disease as defined by the Hoehn &Yahr staging system (Hoehn &Yahr, 1967).
  • Age less than or equal to 75 years.
  • Subjects who are willing and able to provide, in writing, informed consent.
  • Subjects who are willing and able to be confined to the clinical research unit as required by the protocol and to complete all procedures required on an outpatient basis.

Exclusion Criteria:

  • Subjects with evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies and excluding seasonal allergies).
  • Subjects with a history of substance abuse or dependence or a positive urine screen for drugs of abuse.
  • A history of regular alcohol consumption exceeding 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening.
  • Subjects with a documented allergy to methylphenidate or one of the product excipients.
  • Subjects with any medical condition affecting drug absorption (e.g. gastrectomy).
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
  • Use of a monoamine oxidase inhibitor or other interacting medication within the preceding 14 days or 5 half-lives (whichever is longer).
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01244269

Locations
Canada, Quebec
Laval University
Québec, Quebec, Canada, G1V 0A6
Québec Memory and Motor Skills Disorders Research Center
Québec, Quebec, Canada, G1S 2M2
Sponsors and Collaborators
Laval University
Fonds de la Recherche en Santé du Québec
Quebec Memory and Motor Skills Disorders Research Center
Investigators
Study Director: Philippe Corbeil, PhD Laval University
Study Director: Jaime McDonald, BScPhm Laval University
Principal Investigator: Emmanuelle Pourcher, MD Québec Memory and Motor Skills Disorders Research Center
  More Information

No publications provided

Responsible Party: Jaime McDonald, Professeur, Laval University
ClinicalTrials.gov Identifier: NCT01244269     History of Changes
Other Study ID Numbers: MPH.NMS.2011
Study First Received: November 18, 2010
Last Updated: October 19, 2012
Health Authority: Canada: Health Canada

Keywords provided by Laval University:
Parkinson's disease
Methylphenidate
Non motor symptoms
Postural control

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders
Methylphenidate
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014