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: 9648034
• 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 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9648034
• 关键词: Address; Adult; Age; Anti-Cholinergics; Antiparkinson Agents; Area; Behavior Therapy; Behavioral; Benchmarking; Bladder; Bladder Control; Bradykinesia; Brain; CNS processing; Caregiver Burden; Caring; Clinical; Cognitive; Consultations; Disease; Equilibrium; Evaluation; Exercise; Exercise Therapy; Frequencies; Functional Imaging; Future; Gender; General Population; Glare; Goals; Health; Healthcare; Impaired cognition; Impairment; Incontinence; Individual; Institutionalization; International; Intervention; Lead; Learning; Measures; Modeling; Motor Skills; Muscle Contraction; Nervous System control; Neuraxis; Neurodegenerative Disorders; Neuronal Plasticity; Neuropsychology; Nocturia; Outcome; Outcome Measure; Overactive Bladder; Parkinson Disease; Participant; Patients; Pelvic Floor Muscle; Personal Satisfaction; Persons; Pharmaceutical Preparations; Pharmacotherapy; Physical Function; Physical Medicine; Population; Prevalence; Questionnaires; Randomized; Randomized Controlled Trials; Rehabilitation therapy; Research; Risk Factors; Severities; Signal Transduction; Site; Spouse Caregiver; Structure; Symptoms; Time; Training; Tremor; United States; Urge Incontinence; Urinary Incontinence; Veterans; Voice; Woman; afferent nerve; associated symptom; base; behavioral study; burden of illness; cognitive function; common symptom; comparative effectiveness; compare effectiveness; design; disability; evidence base; executive function; falls; improved; men; micturition urgency; 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.

预计到 2030 年，美国帕金森病 (PD) 患者数量将增加一倍 人口年龄。重要的是，帕金森病患病率的增加将在以下领域产生更大的影响： 退伍军人事务部 (VA)，因为退伍军人人口比一般人口年龄大，并且 患有帕金森病的退伍军人比没有患帕金森病的退伍军人更有可能完全依赖退伍军人管理局提供医疗保健。虽然PD是 通常以疾病的运动症状（震颤、运动迟缓、强直）、非运动症状为特征 随着疾病的进展，泌尿系统症状与健康受损的关系更加密切。 然而，帕金森病泌尿系统症状的影响不仅仅限于健康状况恶化。泌尿系统症状 膀胱过度活动症 (OAB)，包括尿急、尿频和夜尿，伴或不伴尿失禁， 是 PD 最常见的泌尿系统症状。 OAB 症状与跌倒有关（跌倒是导致 PD 死亡率增加）、配偶/照顾者压力，以及最终收容机构，因此 至关重要的是，我们要优化患有帕金森病的退伍军人的泌尿系统症状护理。 多项研究表明中枢神经系统对膀胱感觉输入的处理异常 传入神经导致 PD 的 OAB 症状，可能是因为膀胱识别延迟 丰满度。这反映了患有 OAB 的非 PD 人群的发现。在非 PD OAB 人群中，盆底 肌肉收缩会减弱膀胱肌肉的收缩，最近的证据表明行为 盆底肌肉锻炼训练可改善膀胱传入信号的皮质整合。骨盆 针对 OAB 症状的基于地板肌肉运动的行为疗法需要个人学习运动技能 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，基于盆底肌肉锻炼的行为疗法被推荐为一线治疗 患有 OAB 但没有 PD 的男性和女性。然而，最新的临床治疗指南 PD 泌尿系统症状建议使用抗胆碱能药物治疗。虽然有些抗胆碱能药物 虽然可以有效减轻 OAB 症状，但值得注意的是，目前明显缺乏实证研究。 鉴于这些药物增加了抗胆碱能负担，因此在 PD 治疗中推广这些药物的证据基础 抗帕金森病治疗，可能会加重该疾病的认知和自主神经负担。所以， 需要随机对照试验 (RCT) 来优化 PD 泌尿系统症状的治疗范例。 我们建议在亚特兰大（主要地点）、伯明翰和弗吉尼亚州里士满进行三点随机对照试验，以 与药物治疗相比，建立基于盆底肌肉运动的行为疗法的非劣效性 成人 PD 患者的 OAB 症状。将根据 OAB 症状严重程度、PD 运动症状对各组进行分层 严重程度、性别和地点。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 症状评分的功效为 85%，非劣效裕度为 15%。这 主要结果指标是泌尿系统症状的严重程度，由国际咨询会衡量 失禁问卷 (ICIQ) - 在研究期间的 3 个时间点收集的 OAB 症状评分：基线、6 周和 12 周。我们成功治疗的基准是 ICIQ-OAB 降低 ≥ 2 分 症状评分，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。为了评估主要疗效结果，我们将利用随机效应 混合模型并调整基线 OAB 症状评分严重程度。另外，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会产生影响 对基于运动的行为疗法或泌尿系统症状药物疗法的反应。在基线和 12 几周后，随机参与者将接受短暂的神经心理学训练。了解如何域- 特定的认知功能影响对治疗的反应可能会为康复治疗提供新的目标。