Impact of Switching to Continuous Release Dopamine Agonists

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00465452

Enrollment

Registered

2007-04-25

Start date

2007-01-31

Completion date

2011-12-31

Last updated

2025-05-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson Disease

Brief summary

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.

Interventions

DRUGContinuous Release Dopamine Agonists

Continuous Release Dopamine Agonists

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

55 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Unified Parkinson's Disease Rating Scale (UPDRS), Parts 3 (Motor Performance) and 4 (Disability).	initial visit and at end of study 24 weeks	The Unified Parkinson's Disease Rating Scale (UPDRS), parts 3 (motor performance) and 4 (disability) are standardized and validated measures of various symptoms of Parkinson's disease - total scores range from 0 to 148 with lower scores representing better Parkinson symptom control and higher scores representing worse symptoms of Parkinson's.
Mini-Mental Status Exam (MMSE), the Clock Drawing Test (CDT), the Patient Health Questionnaire (PHQ-9).	initial visit and at end of study 24 weeks	The Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) are standardized and validated measures of cognitive function. The Patient Health Questionnaire (PHQ-9) is a standardized and validated measure of quality of life. The Mini-Mental Status Exam (MMSE) scale is 0-30 with higher numbers indicating improvement. The Clock Drawing Test (CDT) range is 0-10 with higher numbers indicating improvement. the PHQ scale is 0-27 with lower numbers indicating improved outcome.
Peripheral Edema, as Measured by Quantitative Assessment of Ankle Edema	initial visit and at end of study 24 weeks	The assessment of ankle edema was considered to be a marker of improvement possibly seen in patients who switched from regular pramipexole to extended release ropinirole. .
Patient Satisfaction Questionnaire	initial visit and at end of study 24 weeks	The patient satisfaction/preference (Patient Satisfaction Questionnaire - PS) scores vary from 0-10 with higher scores indicating greater satisfaction with the med change.
Parkinson's Disease Questionnaire (PDQ-39)	initial visit and at end of study 24 weeks	The Improvement in quality of life (Parkinson's Disease Questionnaire - PDQ-39 - is a standardized and validated measure of patient quality of life ranging in score from 0-100 with lower scores indicating improvement versus higher scores indicating worsening of QOL.

Other

Measure	Time frame	Description
Epworth Sleepiness Scale (ESS).	initial visit and at end of study 24 weeks	Epworth sleepiness scale is a standardized and validated measure of patient's daytime sleepiness. The range of scores is from 0-24 with lower scores representing minimal to no sleepiness and higher scores indicating excessive daytime somnolence.

Countries

United States

Participant flow

Recruitment details

Patients from our outpatient clinic with Parkinson's disease receiving regular pramipexole as one of their treatments and experiencing one or more of the side effects measured in this study.

Participants by arm

Arm	Count
Continuous Release Dopamine Agonist Patients were switched from regular pramipexole to extended release ropinirole	11
Total	11

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1

Baseline characteristics

Characteristic	Continuous Release Dopamine Agonist
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	7 Participants
Age, Categorical Between 18 and 65 years	4 Participants
Age, Continuous	58 years STANDARD_DEVIATION 8.55
Region of Enrollment United States	11 participants
Sex: Female, Male Female	2 Participants
Sex: Female, Male Male	9 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	11 / 11
serious Total, serious adverse events	0 / 11

Outcome results

Primary

Mini-Mental Status Exam (MMSE), the Clock Drawing Test (CDT), the Patient Health Questionnaire (PHQ-9).

The Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) are standardized and validated measures of cognitive function. The Patient Health Questionnaire (PHQ-9) is a standardized and validated measure of quality of life. The Mini-Mental Status Exam (MMSE) scale is 0-30 with higher numbers indicating improvement. The Clock Drawing Test (CDT) range is 0-10 with higher numbers indicating improvement. the PHQ scale is 0-27 with lower numbers indicating improved outcome.