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）：便秘影响多达20％的美国人口，主要是妇女和老年人。受影响的人经历了生活质量受损，大多数人对当前疗法不满意。我们的长期目标是开发疗法来纠正基本多因素功能障碍，并阐明其神经生物学和机械基础。通过以前的应用，我们表明生物反馈改善了患者的排便，并提高了患者的满意度。在这里，我们旨在测试其他功能障碍的新行为处理，并通过将其与机械研究整合在一起，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。我们提出了四个具体目标：1）目前，生物反馈疗法要求熟练的治疗师在生理实验室中使用复杂的设备培训患者。我们开发并测试了电池供电的设备，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。我们将调查和比较100例患有障碍障碍的患者的疗效，成本和结果，并随机分为家庭治疗或基于办公室的治疗。 2）我们的初步研究表明，与对照组相比，患者患者的肠道功能在患者患者中被扰乱，并且生物反馈恢复了正常功能。我们将研究50个失调受试者（生物反馈之前和之后）中肛门直肠脑相互作用的完整性，并通过测量对厌食（传入）和运动诱发的电位（MEP）后的皮质诱发电位（CEP）来比较25个健康对照。 3）目前，不敏直肠的感觉调节涉及用手持注射器重复填充气球。这种尴尬的方法降低了其有效性。我们将在一项随机研究中测试，如果Barostat（压力驱动的计算机系统）训练优于注射器辅助的感觉训练，则在70位具有直肠性不敏的便秘受试者中。此外，我们将通过研究感觉训练之前和之后的肛门直肠感觉运动函数以及CEPS和MEP，检查直肠性低敏的神经脑性低敏敏度机制，并在感觉训练前和之后，并阐明了神经元调节的基因座（中心与外围）。 4）伴有腹痛的便秘通常与直肠超敏反应有关，这种病没有有效的治疗。我们开发并测试了一种新的行为疗法，包括使用Barostat的感觉适应训练（SAT）。在RCT中，我们将与SSRI的SAT进行比较，在60位便秘的IBS患者中，并测试了其减轻疼痛和改善过敏性的功效。这些研究旨在定义并评估障碍性，直肠性低敏性和直肠超敏反应的新疗法的机制，并可能显着影响便秘治疗。