Clinical trial NCT03147599: Mebeverine For 1st Year Daytime And Nocturnal Incontinence After Orthotopic W-Ileal Neobladders
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Oncology
Incontinence
Incontinence, Daytime Urinary
Incontinence, Nighttime Urinary
Bladder Cancer
Orthotopic Neobladder
Keywords: Mebeverine
Incontinence
Orthotopic Neobladder
Lead sponsor: Mansoura University
Sponsor class: OTHER
First posted: 2017-05-10
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Effect of mebeverine on daytime and nocturnal incontinence by assessing continence status measured by standardized continence questionnaire
timeFrame: 10 months
Secondary outcomes:
measure: Effect of mebeverine on patient quality of life by assessing patient quality of life measured by quality of life questionnaire
timeFrame: 10 months
measure: Effect of mebeverine on orthotopic w-ileal neobladders urodynamics by assessing simple urodynamic parameter
timeFrame: 10 months
Other outcomes:
Locations:
city: Mansoura
country: Egypt
facility: Urology and Nephrology Center
state: Aldakahlia
Study officials:
affiliation: Urology and Nephrology Center
name: Hassan Abol-Enein, MD
role: STUDY_CHAIR
affiliation: Urology and Nephrology Center
name: Ahmed Mosbah, MD
role: STUDY_DIRECTOR
affiliation: Urology and Nephrology Center
name: Ahmed Elhussein, MBBCH
role: PRINCIPAL_INVESTIGATOR
affiliation: Urology and Nephrology Center
name: Ahmed Elkarta, MBBCH
role: PRINCIPAL_INVESTIGATOR
affiliation: Urology and Nephrology Center
name: Mohamed Soltan, MBBCH
role: PRINCIPAL_INVESTIGATOR
References: