Mebeverine For 1st Year Daytime And Nocturnal Incontinence After Orthotopic W-Ileal Neobladders

Mebeverine For Daytime And Nocturnal Incontinence and After Orthotopic W-Ileal Neobladders - Assessment Of Efficacy And Quality Of Life Effect Within 1 Year Post-Surgery: A Randomized Controlled Study

A randomized controlled trial to assess clinically the efficacy of the selective ileum spasmolytic mebeverine on daytime incontinence and nocturnal enuresis of orthotopic w-ileal neobladders and quality of life effect within 1 year post-surgery.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer; Oncology; Incontinence; Incontinence, Daytime Urinary; Incontinence, Nighttime Urinary; Orthotopic Neobladder
• Intervention / Treatment: Drug: Placebo; Drug: Coloverin

Detailed Description

In appropriately selected patients an orthotopic neobladder (ONB) permits the elimination of an external stoma and preservation of body image without compromising cancer control after radical cystectomy. Voiding dysfunction (VD) following ONB can be divided into failure to empty bladder or failure to store urine. Failure to empty bladder by angulation of urethra is the most common cause. Failure to store urine can occur during daytime, night-time or both. VD that persists beyond 6 to 12 months warrants urodynamics evaluation to determine the cause and suggest plane of therapy. Voiding dysfunction has a detrimental impact on quality of life.

Among the various bowel segments studied, the ileum is ideal for ONB creation. A spherical reservoir, reconfigured from a de-tubularized ileal segment, offers the most desirable attributes like, adequate capacity, low intraluminal pressure, and good compliance. The patient of ONB reported 4-25% rate of clean intermittent self-catheterisation (CISC) for incomplete emptying. Daytime incontinence was present in 13% of patients. The rate of nocturnal incontinence is usually higher in the range of 15-40% in recent metanalysis. The success of ONB rely on detubularization of intestinal segment, sufficient capacity and proper configuration and position in the pelvis. Adequate capacity is achieved by using sufficient length, folding, and creation an ellipsoid or spherical configuration. The ONB should hold approximately 500 cc of urine at low pressure (at < 15 cm H2O), empty completely (< 100 cc urine), four to five times daily and allow the patient to sleep without awakening, while maintain normal body image

loss of the vesico-urethral reflex 'guarding reflex' in which increased urethral sphincter tone parallel to bladder distension, decreased patient vigilance during sleep resulting in reduced muscle tone and urethral closing pressure, decreased sensitivity of the membranous urethra after radical cystectomy, involuntary high-amplitude contractions of the reservoir secondary to bowel peristalsis and shifting of free water from the reservoir wall into the hyperosmolar urine are the main factor causing global and nocturnal polyuria in patient with ONB. Final, there is also evidence suggesting an increase in bowel activity during sleep. Maximum urethral closing pressure (MUCP) is the primary component responsible for daytime continence in patients with an ONB. However, Koraitim et al. suggest that nocturnal incontinence depends on three reservoir parameters: maximal contraction amplitude, baseline reservoir pressure at mid capacity, and MUCP.

Mebeverine is a derivative of reserpine, which has relatively specific effects on smooth muscle cells without atropine-like side effects in humans. It directly blocks voltage-operated sodium channels and inhibits intracellular calcium accumulation. It is three times more potent than papaverine in inhibiting the peristaltic reflex of the ileum.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Aldakahlia
    • Mansoura, Aldakahlia, Egypt, 35516
      • Urology and nephrology center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men 18 years or older
2. ONB within 1 year post-surgery.

Exclusion Criteria:

1. Upper urinary tract deterioration
2. Uncontrolled diabetes mellitus
3. Evident local or pelvic recurrence
4. Adjuvant chemotherapy
5. Chronic retention
6. Pouch stones
7. Urethral stricture or urethro-ileal maldirection
8. Sensitivity to Mebeverine
9. Untreated chronic constipation
10. Active symptomatic urinary infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Active Comparator: Mebeverine; Coloverin (Mebeverine hydrochloride 135 mg)	Drug: Coloverin; Mebeverine hydrochloride 135 mg; Other Names: Mebeverine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of mebeverine on daytime and nocturnal incontinence by assessing continence status measured by standardized continence questionnaire	Outcome Measure by standardized continence questionnaire	10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of mebeverine on patient quality of life by assessing patient quality of life measured by quality of life questionnaire	Outcome Measure by quality of life questionnaire	10 months
Effect of mebeverine on orthotopic w-ileal neobladders urodynamics by assessing simple urodynamic parameter	Outcome Measure by pressure change measurement in centimetre of water.	10 months

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Study Director: Ahmed Mosbah, MD, Urology and nephrology center; Principal Investigator: Ahmed Elhussein, MBBCH, Urology and nephrology center; Principal Investigator: Ahmed Elkarta, MBBCH, Urology and nephrology center; Study Chair: Hassan Abol-Enein, MD, Urology and nephrology center; Principal Investigator: Mohamed Soltan, MBBCH, Urology and nephrology center

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2017
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: March 15, 2017
• First Submitted That Met QC Criteria: May 8, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 28, 2020
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Incontinence; Mebeverine; Orthotopic Neobladder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Urologic Diseases; Urination Disorders; Elimination Disorders; Enuresis; Nocturnal Enuresis; Diurnal Enuresis; Physiological Effects of Drugs; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Anticonvulsants; Mebeverine
• Other Study ID Numbers: R/17.02.32

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: meta-analyses by contact the Prof. Hassan Abol-Enein, MD, Phd (Study Chair)

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