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

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.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 65

Contacts and Locations

• Study Contact: Name: MARIA CHIARA SIGHINOLFI, DR; Phone Number: 0039 3921329216; Email: mariachiara.sighinolfi@policlinicogemelli.it

Study Locations

• Italy
  • Rome, Italy
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 100168 - Roma
    • Contact: Maria Chiara Sighinolfi, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with bladder cancer scheduled for elective resection surgery at the reference center, specifically the U.O.C. di Clinica Urologica at Fondazione Policlinico Universitario A. Gemelli in Rome, will be enrolled

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Time of in vitro organ bath pharmacological assessment (during the 30-month study period, post-tissue collection)

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Maria Chiara Sighinolfi, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: April 15, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: 8157

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No