Parkinson Disease (PD)
Conditions
Keywords
Parkinson disease, overactive bladder, antimuscarinic, deprescribing, cognitive function, quality of life
Brief summary
This is an unblinded, non-randomized National Institute of Health (NIH) Stage I of Behavioral Intervention Development trial. The investigators will enroll 20 subjects with Parkinson disease (PD) for a series of 20 of N-of-1 trials. The investigators will use a single-arm crossover titration/reversal design ("ON" \[A\] vs. "OFF" \[B\]) with up to 4 periods. All participants will follow the sequence ABAB. Each period will last up to 10 weeks, allowing for sufficient time for up-titration and onset of drug action, and down-titration and washout. Each participant will have the option to participate in less (2-3) or more (3-4) periods depending on whether additional information is needed to make an informed decision about continuing or discontinuing the overactive bladder (OAB) antimuscarinic at the end of the study. The intervention drug will be an OAB antimuscarinic, previously prescribed to the participants by their physician. The investigators will reduce the dose of each OAB antimuscarinic by 25-50% every 1-2 weeks during the "OFF" \[B\] period, with the goal to completely discontinue the medication.
Interventions
DRUGOveractive bladder antimuscarinic deprescribing
During the "ON" \[A\] period (up to 10 weeks), the participant will continue taking their overactive bladder antimuscarinic at their maintenance dose. During the "OFF" \[B\] period (i.e., deprescribing), which will last up to 10 weeks, the antimuscarinic dose will be gradually tapered by 25%-50% every 1-2 weeks until the lowest effective dose or complete discontinuation is achieved. Alternative treatment with mirabegron (pharmacologic) may be initiated, as clinically indicated, if the participant experiences intolerable recurrence of overactive bladder symptoms after discontinuation of the antimuscarinic.
Sponsors
Corporal Michael J. Crescenz VA Medical Center
National Institute on Aging (NIA)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
All participants will follow the AB(AB) sequence.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 60+ years old at time of enrollment 2. Have a diagnosis of Parkinson disease (PD) made by a movement disorders specialist 3. Life expectancy of at least six months 4. Are on an antimuscarinic for overactive bladder (OAB) symptoms (without concurrent use of a beta-3 agonist) for at least 3 months 5. Are able to provide informed consent 6. Are able to complete online surveys/questionnaires 7. Are able to receive telephone calls and Zoom calls/telehealth meeting
Exclusion criteria
1. Have untreated or uncontrolled hypertension (blood pressure \[BP\] ≥180/110 mmHg), 2. Have active urinary tract infection (UTI) or chronic/recurrent UTI (≥2 UTIs in six months or ≥3 in one year) 3. Have moderate or severe hepatic impairment (Child-Pugh Score Class B or C) 4. Have severe renal impairment (Estimated Glomerular Filtration Rate \[eGFR\] \<30 mL/min/1.72 m2) or end-stage renal disease (on dialysis or renal replacement therapy) 5. Have prior history of hypersensitivity or intolerance to mirabegron or vibegron 6. Have existing cognitive impairment (Montreal Cognitive Assessment \[MoCA\] score \<22/30) or psychiatric disorder that preclude informed consent 7. Have any other condition that, in Principal Investigator (PI) and Co-PI's opinion, makes the individual unsuitable for study participation 8. On non-oral form of OAB antimuscarinics, the oral solution formulation of oxybutynin chloride or the oral suspension formulation of solifenacin succinate (due to complicated tapering process)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of deprescribing overactive bladder antimuscarinics on cognitive function | MoCA scores will be assessed at baseline (Visit 0) and at the completion of the study (Visit 41 or up to 46 weeks from baseline). | The investigators will evaluate the effects of deprescribing overactive bladder (OAB) antimuscarinics in individuals with Parkinson disease (PD) on their cognitive function, as measured by the change in participant's cognitive function using the Montreal Cognitive Assessment (MoCA) when they are "ON" vs. "OFF" antimuscarinics. The MoCA score ranges from 0 to 30, with higher scores indicating better cognitive function and lower scores indicating greater cognitive impairment. |
| Effects of deprescribing overactive bladder antimuscarinics on autonomic symptom burden | SCOPA-AUT scores will be assessed at baseline (Visit 0) and at the completion of the study (Visit 41 or up to 46 weeks after baseline). | The investigators will evaluate the effects of deprescribing overactive bladder (OAB) antimuscarinics in individuals with Parkinson disease (PD) on autonomic symptom burden, as measured by the change in participant's Scales for Outcomes in Parkinson's - autonomic (SCOPA-AUT) when they are "ON" vs. "OFF" antimuscarinics. SCOPA-AUT total score ranges from 0 to 69, with higher scores indicating greater autonomic symptom burden and worse autonomic dysfunction. |
| Effects of deprescribing overactive bladder antimuscarinics on quality of life | QOL will be assessed at will be made at baseline (visit 0) and at the completion of the study (Visit 41 or up to 46 weeks from baseline). | The investigators will evaluate the effects of deprescribing overactive bladder (OAB) antimuscarinics in individuals with Parkinson disease (PD) on participant's quality of life (QOL), as measured by the change in participant's global impression of change using participant's QOL questionnaires when they are "ON" vs. "OFF" antimuscarinics. The baseline and end-of-study QOL questionnaires include questions about participant's current overall QOL (0=very poor, 1=poor, 2=fair, 3=good, 4=very good), current bladder-related QOL (0=very poor, 1=poor, 2=fair, 3=good, 4=very good), and current overall well-being affected by side effects of antimuscarinics (0=extremely, 1=quite a bit, 2=moderately, 3=a little, 4=not at all, 5=not applicable). The end-of-study QOL questionnaire include a question about overall state of health since the start of the study (0=very much worse, 1=minimally worse, 2=no change, 3=minimally improved, 4=very much improved). Higher scores indicate better QOL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Features of a feasible and pragmatic protocol for deprescribing N-of-1 trials | These elements will be estimated at the conclusion of the study, once all participants have completed study participation (after Visit 41 or after week 46 from baseline). | Feasibility and pragmatic features of a deprescribing N-of-1 trial protocol for older adults with Parkinson disease (PD) receiving chronic overactive bladder (OAB) antimuscarinics in a neurology specialty center will be evaluated using measures including, but not limited to, enrollment rate (participants enrolled/participants approached), retention rate (participants retained through study completion/participants enrolled), study adherence (participants attending 100% of scheduled visits and completing at least 90% of required assessments during the study period/participants enrolled), and time to study completion (weeks from enrollment to trial completion). |
| Associations between participant and health system characteristics and attitudes toward deprescribing (i.e., satisfaction with current medications) | At baseline (Visit 0) and at the completion of the study (Visit 41 or up to week 46 after baseline) | The investigators will explore the association between participant and health system characteristics and their satisfaction with current medication as measured by the Revised Patient Attitudes toward Deprescribing (rPATD) Questionnaire, when possible. The rPATD reports attitudes across 4 domains (burden, appropriateness, concerns about stopping, and involvement), and 2 global questions evaluating satisfaction with current medications and willingness to stop medication(s) if recommended by a physician. Scores range from 0-4, and higher scores indicate stronger agreement with the construct (e.g., greater perceived medication burden, stronger belief in medication inappropriateness, greater concerns about stopping, or greater desire for involvement, greater satisfaction with current medications and greater willingness to stop). The investigators will use participant's answer on satisfaction with current medications for this association. |
| Associations between participant and health system characteristics and attitudes toward deprescribing (i.e., willingness to deprescribe) | At baseline (Visit 0) and at the completion of the study (Visit 41 or up to week 46 after baseline) | The investigators will explore the association between participant and health system characteristics and their willingness to deprescribe as measured by the Revised Patient Attitudes toward Deprescribing (rPATD) Questionnaire, when possible. The rPATD reports attitudes across 4 domains (burden, appropriateness, concerns about stopping, and involvement), and 2 global questions evaluating satisfaction with current medications and willingness to stop medication(s) if recommended by a physician. Scores range from 0-4, and higher scores indicate stronger agreement with the construct (e.g., greater perceived medication burden, stronger belief in medication inappropriateness, greater concerns about stopping, or greater desire for involvement, greater satisfaction with current medications and greater willingness to stop). The investigators will use participant's answer on willingness to deprescribe for this association. |
Countries
United States
Contacts
CONTACTAllison Willis, MD, MS
CONTACTThanh Phuong Pham Nguyen, PharmD, MBA, MSCE
Outcome results
None listed