Behavioral or Solifenacin Therapy for Urinary Symptoms in Parkinson Disease

行为疗法或索利那新疗法治疗帕金森病泌尿系统症状

• 批准号: 10623149
• 负责人: Elizabeth Camille Vaughan
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10623149
• 关键词: Address; Adult; Age; Anti-Cholinergics; Area; Behavior Therapy; Behavioral; Benchmarking; Bladder; Bladder Control; Bradykinesia; Brain; CNS processing; Caring; Central Nervous System; Cholinergic Agents; Clinical; Cognitive; Consultations; Diagnosis; Disease; Disease Progression; Equilibrium; Evaluation; Exercise; Exercise Therapy; Frequencies; Functional Imaging; Future; Gender; General Population; Goals; Healthcare; Impaired cognition; Impairment; Incontinence; Individual; Institutionalization; International; Intervention; Lead; Learning; Measures; Modeling; Motor Skills; Muscle Contraction; Nervous System control; Neurodegenerative Disorders; Neuronal Plasticity; Neuropsychology; Nocturia; Outcome; Outcome Measure; Overactive Bladder; Parkinson Disease; Parkinsonian Disorders; Participant; Patients; Pelvic Floor Muscle; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacotherapy; Physical Function; Physical Medicine; Population; Prevalence; Questionnaires; Randomized; Randomized, Controlled Trials; Recommendation; Rehabilitation therapy; Research; Risk Factors; Severities; Signal Transduction; Site; Spouses; Symptoms; Time; Training; Tremor; United States; United States Department of Veterans Affairs; Urinary Incontinence; Veterans; Voice Training; Woman; afferent nerve; associated symptom; behavioral study; burden of illness; caregiver stress; cognitive function; common symptom; comparative effectiveness; compare effectiveness; design; disability; efficacy outcomes; evidence base; executive function; falls; imaging study; improved; men; micturition urgency; military veteran; mortality; motor disorder; motor skill learning; motor symptom; neuromechanism; non-motor symptom; novel strategies; patient safety; primary outcome; reduce symptoms; research and development; response; sensory input; treatment guidelines; treatment optimization; treatment response; urinary

The number of persons with Parkinson Disease (PD) in the United States is expected to double by 2030 as the population ages. Importantly, this increase in the prevalence of PD will have greater impact within the Department of Veterans Affairs (VA) because the Veteran population is older than the general population and Veterans with PD are more likely than those without PD to rely solely on VA for their health care. While PD is often characterized by the motor symptoms of the disease (tremor, bradykinesia, rigidity), non-motor symptoms such as urinary symptoms correlate more closely with impaired well-being as the disease progresses. However, the impact of urinary symptoms in PD extends beyond worsened well-being. The urinary symptoms of overactive bladder (OAB), including urgency, frequency, and nocturia, with or without urinary incontinence, are the most common urinary symptoms of PD. OAB symptoms are associated with falls (a cause of increased mortality in PD), with spouse/caregiver stress, and, ultimately with institutionalization, thus it is critical that we optimize the care of urinary symptoms for Veterans with PD. Several studies suggest abnormal central nervous system processing of sensory input from bladder afferent nerves contributes to OAB symptoms in PD, possibly because of delayed recognition of bladder fullness. This mirrors findings in non-PD populations with OAB. In the non-PD OAB population, pelvic floor muscle contractions diminish bladder muscle contraction and recent evidence demonstrates that behavioral training with pelvic floor muscle exercises improves the cortical integration of bladder afferent signals. Pelvic floor muscle exercise-based behavioral therapy for OAB symptoms requires individuals to learn a motor skill and implement an adaptive behavioral strategy to delay the need to void. Because of its effectiveness compared to drug therapy, pelvic floor muscle exercise-based behavioral therapy is recommended first-line in men and women with OAB who do not have PD. However, the most recent clinical guidelines for the treatment of urinary symptoms in PD recommend treatment with anticholinergic drugs. While some anticholinergic drugs are effective in reducing symptoms of OAB, it is important to note that there is a glaring lack of an empirical evidence base to promote these drugs in the setting of PD given that they add to the anticholinergic burden of antiparkinsonian therapy, and may worsen the cognitive and autonomic burdens of the illness. Therefore, randomized controlled trials (RCTs) are needed to optimize treatment paradigms for urinary symptoms in PD. We propose a three-site, RCT conducted at the Atlanta (lead site), Birmingham and Richmond VA's to establish non-inferiority of pelvic floor muscle exercise-based behavioral therapy compared to drug therapy for OAB symptoms in adults with PD. Groups will be stratified by OAB symptom severity, PD motor symptom severity, gender, and site. We will randomize 90 participants in order to complete the study in 80 participants, assuming 85% power and a non-inferiority margin for the OAB symptom score of 15% at 12-weeks. The primary outcome measure will be urinary symptom severity as measured by the International Consultation on Incontinence Questionnaire(ICIQ)-OAB symptom score collected at 3 time points during the study: baseline, 6 weeks, and 12 weeks. Our benchmark for successful treatment will be a ≥ 2 point reduction in the ICIQ-OAB symptom score, which corresponds with perceived benefit in preliminary studies of behavioral therapy treatment for OAB symptoms in PD. To evaluate the primary efficacy outcome, we will utilize a random effects mixed model and adjust for baseline OAB symptom score severity. Additionally, in order to better understand central control mechanisms of bladder function, we will determine if domain-specific cognitive function impacts the response to exercise-based behavioral therapy or drug therapy for urinary symptoms. At baseline and 12 weeks, randomized participants will undergo a brief neuropsychological battery. Understanding how domain- specific cognitive function impacts response to treatment may inform new targets for rehabilitation therapy.

美国帕金森病（PD）患者的数量预计到2030年将翻一番， 人口老龄化。重要的是，PD患病率的增加将对患者产生更大的影响。 退伍军人事务部（VA），因为退伍军人人口比一般人口年龄大， 患有PD的退伍军人比没有PD的退伍军人更有可能完全依赖VA进行医疗保健。当PD 通常以疾病的运动症状（震颤、运动迟缓、僵硬）、非运动症状 例如泌尿系统症状随着疾病的进展与健康受损更密切相关。 然而，PD中泌尿系统症状的影响超出了健康状况的恶化。泌尿系统症状 膀胱过度活动症（OAB），包括尿急、尿频和尿失禁，伴或不伴尿失禁， 是PD最常见的泌尿系统症状。OAB症状与福尔斯有关（OAB的一个原因是 PD的死亡率增加），配偶/照顾者压力，并最终与制度化，因此，它是 关键是我们要优化对患有PD的退伍军人的泌尿系统症状的护理。 一些研究表明，中枢神经系统对膀胱感觉输入的处理异常 传入神经有助于PD患者的OAB症状，可能是因为膀胱识别延迟 丰满这反映了OAB非PD人群的结果。在非PD OAB人群中， 肌肉收缩减少膀胱肌肉收缩，最近的证据表明， 骨盆底肌肉锻炼的训练改善了膀胱传入信号的皮质整合。盆腔 针对OAB症状的基于地板肌肉运动的行为疗法需要个体学习运动技能 并实施适应性行为策略来延迟排尿的需要。因为它的有效性 与药物治疗相比，骨盆底肌肉运动为基础的行为治疗是推荐的一线治疗。 没有PD的OAB男性和女性。然而，最新的治疗临床指南 的PD泌尿系统症状建议抗胆碱能药物治疗。一些抗胆碱能药物 有效地减少OAB的症状，重要的是要注意到， 在PD背景下推广这些药物的证据基础，因为它们增加了PD患者的抗胆碱能负担。 抗帕金森病治疗，并可能恶化的认知和自主负担的疾病。因此，我们认为， 需要随机对照试验（RCT）来优化PD泌尿系统症状的治疗范式。 我们建议在亚特兰大（牵头研究中心）、伯明翰和里士满VA开展一项三中心RCT， 建立骨盆底肌肉运动为基础的行为治疗与药物治疗相比的非劣效性， 成人PD患者的OAB症状。将按OAB症状严重程度、PD运动症状、 严重程度、性别和部位。我们将随机分配90名参与者，以便在80名参与者中完成研究， 假设12周时OAB症状评分的把握度为85%，非劣效性界值为15%。的 主要的结果指标是泌尿系统症状的严重程度， 抑郁问卷（ICIQ）-在研究期间的3个时间点收集的OAB症状评分：基线，6 周，12周。我们成功治疗的基准是ICIQ-OAB降低≥ 2分 症状评分，这与行为疗法初步研究中的感知益处相对应 治疗PD中的OAB症状。为了评价主要疗效结局，我们将使用随机效应 混合模型并针对基线OAB症状评分严重程度进行调整。此外，为了更好地理解 膀胱功能的中枢控制机制，我们将确定特定领域的认知功能是否影响 对基于运动的行为治疗或药物治疗泌尿系统症状的反应。在基线和12个 周，随机参与者将接受简短的神经心理电池。了解域- 特定的认知功能影响对治疗的反应可能为康复治疗提供新的目标。