Impact of Switching to Continuous Release Dopamine Agonists

The Impact of Switching to Continuous Release Dopamine Agonists on Non-Motor Side Effects

The purpose of this proposal is to determine if switching PD patients treated with pramipexole to ropinirole CR reduces the non-motor side effects frequently experienced by these patients. Side effects that we will monitor in particular include somnolence, peripheral edema, cognitive decline with and without hallucinations. PD patients followed in the MUO Neurology Clinic who are being treated with pramipexole and have evidence of at least one of the following symptoms: somnolence, cognitive impairment with or without hallucinations, or peripheral edema will be offered the opportunity to participate in this study.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Continuous Release Dopamine Agonists

Detailed Description

The purpose of this proposal is to determine if switching PD patients treated with pramipexole to ropinirole CR reduces the non-motor side effects frequently experienced by these patients. Side effects that we will monitor in particular include somnolence, peripheral edema, cognitive decline with and without hallucinations. PD patients followed in the MUO Neurology Clinic who are being treated with pramipexole and have evidence of at least one of the following symptoms: somnolence, cognitive impairment with or without hallucinations, or peripheral edema will be offered the opportunity to participate in this study.

Fifteen subjects who are currently receiving pramipexole therapy (monotherapy or adjunctive therapy) who are experiencing one or more of the following symptoms: somnolence, cognitive decline with/without hallucinations, and peripheral edema will be asked if they are willing to participate at the time of their clinic visit at the PDMDP.

The crossover from pramipexole to ropinirole CR will be performed over a 2 week interval. During the first week, the initial drug dose will substitute ½ of the pramipexole with ½ of the target dose of ropinirole CR. If subjects are tolerating the drug change, then 100% of the target dose of ropinirole CR (and no pramipexole) will be started in the second week.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Each subject must meet all of the following inclusion criteria to qualify for entrance into the study:

• Subjects who are male or female and are aged 55 and older.
• Subjects and/or their legal guardians must be able and willing to give informed consent.
• Subjects must be on stable doses of pramipexole for greater than 4 weeks duration prior to screening.
• Subjects who are female must be non-pregnant and non-nursing. Women of Child-Bearing Potential (WOCBP) must use a reliable method of contraception (e.g., oral contraceptive or long-term injectable or implantable hormonal contraceptive, double-barrier methods, such as condom and diaphragm, condom and foam, condom and sponge or intra-uterine devices) and have a negative serum pregnancy test at screening. Women are considered to not be of child-bearing potential if they have been surgically sterilized (physician-documented hysterectomy or tubal ligation) or if they are post-menopausal.
• Subjects must have a clinical diagnosis of Parkinson's based on the presence of at least 2 of the 3 cardinal criteria - rest tremor, bradykinesia, rigidity - and no obvious history of head trauma, stroke, infectious, structural, or metabolic abnormality consistent with an alternative diagnosis to Parkinson's disease.
• Evidence of one or more of the following symptoms: somnolence (ESS score ≥ 9), cognitive decline (MMSE < 24 ± presence of hallucinations (NPI-Q), peripheral edema (present by objective physical exam with baseline ankle and calf circumference measured in centimeters).

Exclusion Criteria:

A subject who meets any of the following criteria will NOT qualify for the study:

• Subjects must not be receiving any treatments for excess somnolence such as amphetamine derivatives, other stimulants or Provigil.
• Subjects with actively treated malignancies, clinically significant heart disease, kidney, liver, or pulmonary disorders will be excluded.
• Subjects with clinical depression who are not receiving stable doses of antidepressant therapy in excess of 4 weeks duration.
• Subjects with history of orthostatic hypotension (>30mm drop in systolic pressure and/or >20mm drop in diastolic pressure) associated with syncope.
• Subjects started within the last 14 days on any drug known to substantially inhibit CYP1A2 (e.g., cimetidine, fluvoxamine) or induce CYP1A2 (e.g.omeprazole) (Note: Subjects already on these agents may be enrolled but must remain on the stable doses of the agents from 14 days prior to the beginning of the study).
• Subjects who have other medical conditions that are considered clinically unstable or that may compromise the safety of the patient during this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Equal or improved motor scores as measured by the Unified Parkinson's Disease Rating Scale (UPDRS), parts 3 (motor performance) and 4 (disability).	initial visit and repeated at 4, 12, and 24 weeks
A significant improvement in somnolence as measured by the Epworth Sleepiness Scale (ESS).	initial visit and repeated at 4, 12, and 24 weeks
A significant stabilization or improvement in the cognitive/mood battery of the Mini-Mental Status Exam (MMSE), the Clock Drawing Test (CDT), the Patient Health Questionnaire (PHQ-9) and the Neuropsychiatric Inventory Questionnaire (NPI-Q).	initial visit and repeated at 4, 12, and 24 weeks
An improvement in peripheral edema, as measured by quantitative assessment of ankle and calf edema.	initial visit and repeated at 4, 12, and 24 weeks
Increased patient satisfaction/preference (Patient Satisfaction Questionnaire - PS) scores.	initial visit and repeated at 4, 12, and 24 weeks
Improvement in quality of life (Parkinson's Disease Questionnaire - PDQ-39).	initial visit and repeated at 4, 12, and 24 weeks

Collaborators and Investigators

• Sponsor: University of Toledo Health Science Campus
• Investigators: Principal Investigator: Lawrence Elmer, MD, PhD, Medical University of Ohio

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: April 24, 2007
• First Submitted That Met QC Criteria: April 24, 2007
• First Posted (Estimate): April 25, 2007

Study Record Updates

• Last Update Posted (Estimate): March 19, 2009
• Last Update Submitted That Met QC Criteria: March 18, 2009
• Last Verified: March 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Cardiotonic Agents; Dopamine Agents; Sympathomimetics; Dopamine; Dopamine Agonists
• Other Study ID Numbers: MUO-04