Feasibility Testing of Transpelvic Magnetic Stimulation as a Novel Intervention toImprove Urogenital Function in Prostate Cancer Survivors

经盆腔磁刺激作为改善前列腺癌幸存者泌尿生殖功能的新型干预措施的可行性测试

• 批准号: 10249223
• 负责人: MAHADEVAN Raj RAJASEKARAN
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249223
• 关键词: Adherence; Affect; Anatomy; Architecture; Atrophic; Bladder Control; Blood; Blood flow; Cancer Survivor; Cicatrix; Clinic; Clinical Trials; Communication; Complex; Consent; Data; Development; Devices; Diagnostic Imaging; Early Diagnosis; Electronic Mail; Ensure; Erectile dysfunction; Evaluation; Feasibility Studies; Fibrosis; Foundations; Functional disorder; Future; Genitourinary system; Healthcare; Image; Imaging Techniques; Incidence; Inflammation; Injury; Institutional Review Boards; International; Intervention; Intervention Studies; Laser Speckle Imaging; Lasers; Lead; Magnetic Resonance Imaging; Magnetism; Male sexual dysfunction; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Methods; Microcirculation; Monitor; Morphology; Muscle; Muscle function; Muscular Atrophy; Nervous System Trauma; Oncology; Operative Surgical Procedures; Outcome; Outcome Measure; Pain-Free; Participant; Patient Recruitments; Patient Schedules; Patients; Pelvic Floor Muscle; Pelvis; Physiological; Pilot Projects; Placebos; Play; Population; Positioning Attribute; Process; Prostate Cancer therapy; Protocols documentation; Quality of life; Questionnaires; Radiology Specialty; Randomized; Randomized Clinical Trials; Recovery; Recovery of Function; Regulation; Rehabilitation therapy; Reporting; Research; Research Personnel; Retropubic Prostatectomy; Risk Factors; Role; Severities; Sex Functioning; Sexual Dysfunction; Smooth Muscle; Sphincter; Striated Muscles; Surgical Injuries; Symptoms; Techniques; Telephone; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Training; Translational trial; Urethra; Urethral sphincter; Urinary Incontinence; Urologist; Urology; Vascular blood supply; Veterans; Weight; acceptability and feasibility; age related; base; blood perfusion; cancer surgery; cancer type; clinical application; clinical translation; curative treatments; erection; feasibility testing; follow-up; functional disability; hemodynamics; improved; incontinence symptom; indexing; injury recovery; innovation; male; men; military veteran; muscle regeneration; muscle strength; nerve supply; neuroregulation; non-invasive imaging; novel; novel diagnostics; novel imaging technique; novel strategies; penis; pressure; prevent; primary outcome; programs; prostate cancer survivors; prostate surgery; randomized trial; recruit; regeneration function; relating to nervous system; retention rate; secondary outcome; tool; treatment arm; uptake; urinary

The overall purpose of this SPiRE project is to assess the feasibility and acceptability of a novel intervention approach and to collect preliminary data for a future randomized clinical trial to rehabilitate urogenital function in prostate cancer survivors. Prostate cancer is most common in men over 50 years and this cancer incidence is especially high (29%) in the VA patients. With early diagnosis, patients can pursue potentially curative interventions that include surgical procedures (radical retropubic prostatectomy). However, these surgical treatments lead to problems with continence (urinary incontinence: UI) and sexual function (erectile dysfunction- ED, a major form of sexual dysfunction) in as many as 30-70% of these cancer survivors. Although it is recognized that the continence and sexual functions are critical issues affecting quality of life, there has been only limited research into methods to prevent these forms of dysfunction. These derangements are further impacted by age-related atrophy and fibrosis of corpus cavernosum, urethral sphincters, and that of supporting pelvic floor muscles (ischiocavernosus-ICM and puborectalis-PRM). Hence, there is an urgent need for non-invasive innovative approaches for urinary continence and sexual function rehabilitation to prevent this problem in cancer survivors. This proposed feasibility study takes a novel interventional approach, using repetitive Transpelvic Magnetic Stimulation approach (rTPMS) to prevent fibrosis and strengthen the PFM. We propose to recruit VA patients that are scheduled to undergo prostate cancer surgery and perform a randomized interventional study to determine the feasibility of rehabilitation potential of rTPMS. We will estimate number of potentially eligible patients, rate of consent of eligible patients consent rate, overall uptake rate (in relation to the number potentially eligible), retention rate, follow-up rates for questionnaires and adherence to the interventions and imaging protocols. We will first evaluate all the baseline physiological as well as morphological parameters of penis, urethra and pelvic muscles. Primary outcome measures for assessment of UI will be the extent of reduction (%) in the number of UI symptom scores. For assessment of ED, improvement in erectile function as measured by the International Index of Erectile Function (IIEF-5), a validated, 5-item symptom score, will be used. Secondary outcome measures will be pad weight and PFM changes that will be measured by MRI (UTE for fibrosis). For ED, penile blood flow and PFM changes measured by Doppler blood flow, laser speckle contrast imaging and MRI (UTE for fibrosis), respectively. Besides these therapeutic interventions, we also propose to test novel diagnostic tools to monitor blood supply to the penile tissues (by Laser Doppler imaging) and scarring of these muscles (by a new MRI technique, called ultrashort echo time-UTE). Next, we will test if TPMS will enhance blood flow and increase pelvic muscle strength in these men for about 6 months. Patients will be further monitored for 3 more months and subjected to all the described evaluations to determine recovery of continence and sexual functions. Use of rTPMS to promote continence and sexual function rehabilitation remains unexplored. Thus, our future randomized clinical trials will have the potential to identify novel strategies for restoring continence and sexual function after the surgical treatment in prostate cancer survivors. All the proposed novel non-invasive imaging techniques such as MR-UTE (to monitor fibrosis) and the novel hemodynamic technique to monitor penile microvascular function have high potential for future clinical applications. In addition, the proposed rTPMS protocol has significant potential for clinical translation. If this intervention is proven to be efficacious in a future randomized trial, it will have important implications for rehabilitation in the future. Thus, establishing the foundation for a future translational trial is of utmost importance to VA healthcare users.

SPiRE 项目的总体目的是评估新型干预措施的可行性和可接受性 方法并为未来康复泌尿生殖系统的随机临床试验收集初步数据 在前列腺癌幸存者中发挥作用。前列腺癌在 50 岁以上的男性中最常见，这种癌症 VA 患者的发病率尤其高（29%）。通过早期诊断，患者可以寻求潜在的治疗 治疗性干预措施包括外科手术（根治性耻骨后前列腺切除术）。然而，这些 手术治疗会导致失禁（尿失禁：UI）和性功能（勃起）问题 多达 30-70% 的癌症幸存者出现功能障碍（ED，性功能障碍的一种主要形式）。 尽管人们认识到节制和性功能是影响生活质量的关键问题， 对于预防这些形式的功能障碍的方法的研究非常有限。这些乱象 进一步受到与年龄相关的海绵体、尿道括约肌和尿道括约肌萎缩和纤维化的影响 支持盆底肌肉（坐骨海绵体肌-ICM 和耻骨直肠肌-PRM）。因此，迫切需要 寻找尿失禁和性功能康复的非侵入性创新方法来预防这种情况 癌症幸存者的问题。这项拟议的可行性研究采用了一种新颖的干预方法，使用 重复经盆腔磁刺激方法 (rTPMS) 可预防纤维化并增强 PFM。 我们建议招募计划接受前列腺癌手术的 VA 患者并进行 随机介入研究以确定 rTPMS 康复潜力的可行性。我们将 估计潜在合格患者的数量、合格患者的同意率 同意率、总体接受率 率（与可能符合资格的人数有关）、保留率、问卷跟进率以及 遵守干预措施和成像协议。我们将首先评估所有基线生理学 以及阴茎、尿道和骨盆肌肉的形态参数。主要结果指标 UI 的评估将是 UI 症状评分数量的减少程度 (%)。用于评估 ED，根据国际勃起功能指数 (IIEF-5) 测量的勃起功能改善， 将使用经过验证的 5 项症状评分。次要结果指标是垫重量和 PFM 通过 MRI（纤维化 UTE）测量的变化。对于 ED、阴茎血流量和 PFM 变化 分别通过多普勒血流、激光散斑对比成像和 MRI（UTE 用于纤维化）测量。 除了这些治疗干预措施外，我们还建议测试新的诊断工具来监测血液供应 阴茎组织（通过激光多普勒成像）和这些肌肉的疤痕（通过新的 MRI 技术， 称为超短回波时间-UTE）。接下来我们来测试一下TPMS是否会增强血液流动，增加骨盆肌肉 这些人的力量持续了大约六个月。患者将进一步接受 3 个月的监测并接受治疗 进行所有描述的评估以确定节制和性功能的恢复。使用 rTPMS 促进节制和性功能康复仍有待探索。因此，我们未来的随机临床 试验将有可能确定在术后恢复节制和性功能的新策略。 前列腺癌幸存者的手术治疗。所有提出的新型非侵入性成像技术，例如 MR-UTE（监测纤维化）和监测阴茎微血管的新型血流动力学技术 功能在未来的临床应用中具有很大的潜力。此外，所提出的 rTPMS 协议还具有 临床转化的巨大潜力。如果这种干预措施在未来的随机试验中被证明是有效的 试验，对今后的康复具有重要意义。从而奠定了基础 未来的转化试验对于 VA 医疗保健用户至关重要。