跳至主要内容
临床试验/NCT07545694
NCT07545694招募中不适用

Study on the Effects of Drugs That Modulate the Endocannabinoid System on Spontaneous and Induced Contractility of the Human Detrusor Muscle

Fondazione Policlinico Universitario Agostino Gemelli IRCCS1 个研究点 分布在 1 个国家目标入组 65 人开始时间: 2025年11月12日最近更新:
适应症

试验速览

阶段
不适用
状态
招募中
发起方
入组人数
65
试验地点
1
主要终点
Effects of CB receptor agonists, antagonists and allosteric modulators, endocannabinoid synthesis/catabolism enzyme inhibitors, and EMT transporter inhibitors on EFS-induced submaximal contractions of detrusor preparations

研究概览

简要总结

The goal of this observational, in vitro study is to evaluate the effects of drugs that modulate the endocannabinoid system on spontaneous and neuronally induced contractility of the human detrusor. The study will include adult patients undergoing elective radical cystectomy for bladder cancer. The main questions it aims to answer are whether modulation of endocannabinoid receptors, enzymes involved in endocannabinoid synthesis and degradation, and endocannabinoid transport mechanisms alters basal detrusor contractility and modifies excitatory motor responses induced by neuronal activation.

Participants undergoing radical cystectomy will provide written informed consent for the collection of a small sample of macroscopically healthy bladder tissue from the surgical specimen. Detrusor muscle strips will be prepared and studied in vitro using organ bath techniques. Contractile activity will be recorded under baseline conditions and after electrical field stimulation, as well as following exposure to pharmacological modulators of the endocannabinoid system. Demographic, clinical, and pathological data will also be collected for descriptive analysis.

详细描述

This is a prospective, monocentric, observational in vitro study designed to investigate the role of the endocannabinoid system in the regulation of human detrusor contractility. The study evaluates the effects of pharmacological modulation of endocannabinoid receptors, enzymes involved in endocannabinoid synthesis and degradation, and endocannabinoid transport mechanisms on both spontaneous and neuronally induced contractile activity of human detrusor muscle.

The endocannabinoid system has been implicated in the regulation of lower urinary tract function, including sensory signaling and smooth muscle contractility. Experimental evidence suggests that cannabinoid receptor activation may modulate neurotransmitter release and detrusor muscle activity. However, most available data derive from animal models, and findings in human tissues remain limited and sometimes conflicting. A better characterization of the role of endocannabinoid signaling in human detrusor contractility may provide insight into potential therapeutic targets for disorders such as detrusor overactivity and overactive bladder syndrome.

Bladder tissue samples will be obtained from surgical specimens and processed for in vitro functional studies. Detrusor muscle strips will be prepared and mounted in organ baths to record contractile responses under controlled experimental conditions. Baseline motor activity and responses to neuronal stimulation will be assessed. Preparations will then be exposed to pharmacological agents acting on different components of the endocannabinoid system, including receptor agonists and antagonists, allosteric modulators, inhibitors of endocannabinoid biosynthesis and degradation, and inhibitors of endocannabinoid transport. Changes in contractile activity will be evaluated to characterize the functional contribution of these pathways.

The experimental procedures will be conducted in sequential phases to characterize baseline contractile responses, assess receptor-mediated effects, and evaluate the impact of modulation of endocannabinoid metabolism and transport. Clinical and demographic data will be recorded for descriptive purposes. The study is exploratory in nature and aims to generate mechanistic data on the role of the endocannabinoid system in human detrusor physiology.

研究设计

研究类型
Observational
观察模型
Other
时间视角
Prospective

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Age ≥ 18 years.
  • Patients with bladder carcinoma at any stage of disease, undergoing upfront surgery or neoadjuvant therapy for more than 6 weeks, scheduled for surgery with curative/demolitive intent.
  • Signed written informed consent to participate in the study.

排除标准

  • Age < 18 years.
  • Procedures performed on an urgent/emergency basis.
  • Patients treated with corticosteroid therapy for immunorheumatic diseases.
  • Patients treated with radio-chemotherapy and undergoing surgery less than 6 weeks prior.
  • Refusal to sign written informed consent to participate in the study.

结局指标

主要结局

Effects of CB receptor agonists, antagonists and allosteric modulators, endocannabinoid synthesis/catabolism enzyme inhibitors, and EMT transporter inhibitors on EFS-induced submaximal contractions of detrusor preparations

时间窗: Time of in vitro organ bath pharmacological assessment (during the 30-month study period, post-tissue collection)

Evaluate the change in amplitude on submaximal contractions induced by electrical field stimulation (EFS) in human detrusor tissue strips mounted in organ baths following exposure to specified drugs

次要结局

未报告次要终点

研究者

发起方
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
申办方类型
Other
责任方
Sponsor

研究点 (1)

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