Pilot Deprescribing of Antimuscarinic Overactive Bladder Medications in Parkinson Disease

Официальное название

Evaluating the Effect of Deprescribing Antimuscarinic Overactive Bladder Medications on Cognitive Function and Quality of Life of Individuals With Parkinson Disease: A Pharmacist-led Series of N-of-1 Trials

Обзор

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.

Вмешательства

• Препарат Overactive 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 participan

Первичные конечные точки

• Effects of deprescribing overactive bladder antimuscarinics on cognitive function [Срок оценки: 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).]
• Effects of deprescribing overactive bladder antimuscarinics on autonomic symptom burden [Срок оценки: 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).]
• Effects of deprescribing overactive bladder antimuscarinics on quality of life [Срок оценки: 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).]

Вторичные конечные точки (3)

• Features of a feasible and pragmatic protocol for deprescribing N-of-1 trials [Срок оценки: 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).]
• Associations between participant and health system characteristics and attitudes toward deprescribing (i.e., satisfaction with current medications) [Срок оценки: At baseline (Visit 0) and at the completion of the study (Visit 41 or up to week 46 after baseline)]
• Associations between participant and health system characteristics and attitudes toward deprescribing (i.e., willingness to deprescribe) [Срок оценки: At baseline (Visit 0) and at the completion of the study (Visit 41 or up to week 46 after baseline)]

Критерии участия

Критерии включения

• 60+ years old at time of enrollment
• Have a diagnosis of Parkinson disease (PD) made by a movement disorders specialist
• Life expectancy of at least six months
• Are on an antimuscarinic for overactive bladder (OAB) symptoms (without concurrent use of a beta-3 agonist) for at least 3 months
• Are able to provide informed consent
• Are able to complete online surveys/questionnaires
• Are able to receive telephone calls and Zoom calls/telehealth meeting

Критерии исключения

• Have untreated or uncontrolled hypertension (blood pressure \[BP\] ≥180/110 mmHg),
• Have active urinary tract infection (UTI) or chronic/recurrent UTI (≥2 UTIs in six months or ≥3 in one year)
• Have moderate or severe hepatic impairment (Child-Pugh Score Class B or C)
• 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)
• Have prior history of hypersensitivity or intolerance to mirabegron or vibegron
• Have existing cognitive impairment (Montreal Cognitive Assessment \[MoCA\] score <22/30) or psychiatric disorder that preclude informed consent
• Have any other condition that, in Principal Investigator (PI) and Co-PI's opinion, makes the individual unsuitable for study participation
• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 1 центр

• Corporal Michael J. Crescenz VA Medical Center — Philadelphia

Публикации

• Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015 Mar;175(3):401-7. doi: 10.1001/jamainternmed.2014.7663. PMID 25621434
• Abraham DS, Pham Nguyen TP, Newcomb CW, Gray SL, Hennessy S, Leonard CE, Liu Q, Weintraub D, Willis AW. Comparative safety of antimuscarinics versus mirabegron for overactive bladder in Parkinson disease. Parkinsonism Relat Disord. 2023 Oct;115:105822. doi: 10.1016/j.parkreldis.2023.105822. Epub 2023 Sep 4. PMID 37713748
• Abraham DS, Pham Nguyen TP, Hennessy S, Weintraub D, Gray SL, Xie D, Willis AW. Frequency of and risk factors for potentially inappropriate medication use in Parkinson's disease. Age Ageing. 2020 Aug 24;49(5):786-792. doi: 10.1093/ageing/afaa033. PMID 32255485
• Goyal P, Safford MM, Hilmer SN, Steinman MA, Matlock DD, Maurer MS, Lachs MS, Kronish IM. N-of-1 trials to facilitate evidence-based deprescribing: Rationale and case study. Br J Clin Pharmacol. 2022 Oct;88(10):4460-4473. doi: 10.1111/bcp.15442. Epub 2022 Jul 13. PMID 35705532

Идентификаторы

NCT: NCT07627529 · 1889946-4 · R33AG086944

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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