Clinical trial NCT00465452: Impact of Switching to Continuous Release Dopamine Agonists
Official title: The Impact of Switching to Continuous Release Dopamine Agonists on Non-Motor Side Effects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease
Lead sponsor: University of Toledo
Sponsor class: OTHER
First posted: 2007-04-25
Enrollment: 11
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Unified Parkinson's Disease Rating Scale (UPDRS), Parts 3 (Motor Performance) and 4 (Disability).
timeFrame: initial visit and at end of study 24 weeks
measure: Mini-Mental Status Exam (MMSE), the Clock Drawing Test (CDT), the Patient Health Questionnaire (PHQ-9).
timeFrame: initial visit and at end of study 24 weeks
measure: Peripheral Edema, as Measured by Quantitative Assessment of Ankle Edema
timeFrame: initial visit and at end of study 24 weeks
measure: Patient Satisfaction Questionnaire
timeFrame: initial visit and at end of study 24 weeks
measure: Parkinson's Disease Questionnaire (PDQ-39)
timeFrame: initial visit and at end of study 24 weeks
Secondary outcomes:
Other outcomes:
measure: Epworth Sleepiness Scale (ESS).
timeFrame: initial visit and at end of study 24 weeks
Locations:
city: Toledo
country: United States
facility: Medical University of Ohio
state: Ohio
Study officials:
affiliation: Medical University of Ohio
name: Lawrence Elmer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: