Novel Treatment Strategies for Constipation and Role of Brain-Gut axis

便秘的新治疗策略和脑肠轴的作用

• 批准号: 7884281
• 负责人: Satish SC Rao
• 金额: $ 29.83万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7884281
• 关键词: Abdomen; Abdominal Pain; Address; Advocate; Affect; Antidepressive Agents; Anus; Ataxia; Attention; Behavior; Behavior Therapy; Biofeedback; Biological; Brain; Client satisfaction; Communities; Conflict (Psychology); Constipation; Data; Defecation; Devices; Dietary Factors; Digestive System Disorders; Effectiveness; Elderly woman; Electric Stimulation; Equipment; Escitalopram; Esthesia; Evoked Potentials; Feces; Feedback; Functional disorder; Goals; Grant; Hand; Home environment; Hypersensitivity; Individual; Intestines; Irritable Bowel Syndrome; Laboratories; Learning; Measures; Methods; Motor; Motor Evoked Potentials; Nature; Neurons; Outcome; Pain; Patients; Perception; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Physiology; Population; Quality of life; Randomized; Randomized Controlled Trials; Rectum; Reflex action; Refractory; Research Personnel; Role; Selective Serotonin Reuptake Inhibitor; Self-Administered; Sensory; Sensory Thresholds; Signal Transduction; Simulate; Surveys; Symptoms; Syringes; System; Testing; Therapeutic; Training; Training Programs; Transcranial magnetic stimulation; base; comparative efficacy; computerized; conditioning; coping; cost; design; effective therapy; efficacy testing; experience; functional improvement; functional restoration; improved; indexing; instrumentation; multidisciplinary; neuromuscular; novel; pressure; programs; psychologic; rectal; rectum/anus; response; satisfaction; therapy development; treatment strategy

DESCRIPTION (provided by applicant): Constipation affects up to 20% of the US population, mainly women and the elderly. Affected individuals experience impaired quality of life and most are dissatisfied with current therapy. Our long-term goals are to develop therapies that remedy the underlying multifactorial dysfunction(s), and elucidate their neurobiologic and mechanistic bases. Through the previous application, we showed that biofeedback improved dyssynergic defecation and led to superior patient satisfaction. Here we aim to test new behavioral treatments for other dysfunctions and by integrating this with mechanistic studies we can reveal how the brain and the gut (gut- brain axis) interact, and how biofeedback modulates cortico-rectal function. We propose four specific aims: 1) Currently, biofeedback therapy requires a skilled therapist to train a patient using sophisticated equipment in a physiologic laboratory. We developed and tested a battery powered device for patients to use in their own home. We will determine if a community-based biofeedback therapy is as effective as laboratory- based biofeedback therapy. We will investigate and compare the efficacy, costs and outcomes of 100 patients with dyssynergic defecation, randomized to either home therapy or office-based therapy. 2) Our preliminary studies revealed that gut-brain function is deranged in dyssynergic patients, compared to controls and that biofeedback restores normal function. We will investigate the integrity of anorectal-brain interactions in 50 dyssynergic subjects (before and after biofeedback) and compare this with 25 healthy controls by measuring the cortical evoked potentials (CEP) after electrical stimulation of the anorectum (afferent) and the motor evoked potentials (MEP) following transcranial magnetic stimulation (efferent). 3) Currently, sensory conditioning of a hyposensitive rectum involves repetetive filling of a balloon with a hand-held syringe; this awkward approach reduces its effectiveness. We will test, in a randomized study, if barostat (pressure-driven computerized system) training is superior to syringe-assisted sensory training, in 70 constipated subjects with rectal hyposensitivity. Also, we will examine the neuroenteric mechanism(s) of rectal hyposensitivity by investigating anorectal sensori-motor function as well as CEPs and MEPs, before and after sensory training, and elucidate the locus (central versus peripheral) for neuronal modulation. 4) Constipation accompanied by abdominal pain is commonly associated with rectal hypersensitivity, a condition with no effective therapy. We developed and tested a new behavioral therapy, comprising of sensory adaptation training (SAT) using a barostat. In a RCT, we will compare SAT with escitalopram, a SSRI, in 60 constipated IBS patients and test its efficacy in reducing pain and improving hypersensitivity. These studies aim to define the mechanisms of, and evaluate new therapies for dyssynergia, rectal hyposensitivity and rectal hypersensitivity, and could significantly impact constipation treatments.

描述（由申请人提供）： 多达 20% 的美国人口受到便秘的影响，主要是女性和老年人。受影响的个体生活质量受损，大多数人对当前的治疗不满意。我们的长期目标是开发治疗潜在的多因素功能障碍的疗法，并阐明其神经生物学和机制基础。通过之前的应用，我们表明生物反馈改善了排便失调并带来了较高的患者满意度。在这里，我们的目标是测试针对其他功能障碍的新行为疗法，通过将其与机制研究相结合，我们可以揭示大脑和肠道（肠脑轴）如何相互作用，以及生物反馈如何调节皮质直肠功能。我们提出四个具体目标：1）目前，生物反馈疗法需要熟练的治疗师在生理实验室使用先进的设备来训练患者。我们开发并测试了一种电池供电的设备，供患者在自己的家中使用。我们将确定基于社区的生物反馈疗法是否与基于实验室的生物反馈疗法一样有效。我们将调查并比较 100 名排便失调患者的疗效、费用和结果，这些患者随机接受家庭治疗或办公室治疗。 2）我们的初步研究表明，与对照组相比，协同失调患者的肠脑功能紊乱，而生物反馈可以恢复正常功能。我们将研究 50 名协同失调受试者（生物反馈前后）的肛门直肠-大脑相互作用的完整性，并通过测量电刺激肛门直肠（传入）后的皮质诱发电位 (CEP) 和运动诱发电位，将其与 25 名健康对照进行比较(MEP) 经颅磁刺激（传出）后。 3) 目前，对低敏感直肠的感觉调节涉及用手持式注射器重复填充气球；这种笨拙的方法降低了其有效性。我们将在一项随机研究中测试恒压器（压力驱动计算机系统）训练是否优于注射器辅助感觉训练，测试对象为 70 名患有直肠敏感性低下的便秘受试者。此外，我们将通过研究感觉训练前后的肛门直肠感觉运动功能以及 CEP 和 MEP 来检查直肠敏感性低下的神经肠机制，并阐明神经元调节的部位（中枢与外周）。 4) 伴有腹痛的便秘通常与直肠过敏有关，这种情况没有有效的治疗方法。我们开发并测试了一种新的行为疗法，包括使用恒压器的感觉适应训练（SAT）。在一项 RCT 中，我们将在 60 名便秘 IBS 患者中比较 SAT 与艾司西酞普兰（一种 SSRI），并测试其在减轻疼痛和改善过敏方面的功效。这些研究旨在确定协同失调、直肠敏感性低下和直肠过敏的机制并评估新疗法，并可能显着影响便秘治疗。