Effects of Single Dose Citalopram and Reboxetine on Urethral and Anal Closure Function on Healthy Female Subjects

NCT04097288 | Completed Phase 1 DMC

• 2 other identifiers: SSRI-UPR-012019-000059-14
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate if citalopram, a selective serotonin reuptake inhibitor, is reducing the opening pressure of the urethra and possibly causing or worsening stress urinary incontinence. Reboxetine, a norepinephrine reuptake inhibitor, is known to increase urethral opening pressure through actions on adrenoceptors in Onuf´s nucleus and will act as an active control. Furthermore, this study is performed to explore the effects of reboxetine and citalopram on the opening pressure of the anal canal.

Conditions

Stress Urinary Incontinence; Fecal Incontinence

Keywords

stress urinary incontinence; pharmacologic treatment; fecal incontinence

Outcome Measures

Primary Outcomes (2)

• Difference in average UOP-placebo and average UOP-citalopram (during relaxation)

  Difference in urethral opening pressure

  UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine

• Difference in average AOP-placebo and average AOP-citalopram or average AOP-reboxetine (during relaxation)

  Difference in urethral opening pressure

  UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine

Secondary Outcomes (3)

• Difference in average UOP-placebo and average UOP-reboxetine (during relaxation)

  UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine

• Difference in average UOP-placebo and average UOP-citalopram or UOP-reboxetine (during voluntary contraction)

  UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine

• Difference in average AOP-placebo and average AOP-citalopram or AOP-reboxetine (during voluntary contraction).

  UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine

Study Arms (4)

Single dose citalopram

EXPERIMENTAL

A blinded single dose 40 mg citalopram is administered three hours before urethral pressure reflectometry and anal acoustic reflectometry measurements

Drug: Citalopram 40mg

Single dose reboxetine

ACTIVE COMPARATOR

A blinded single dose 8 mg reboxetine is administered two hours before urethral pressure reflectometry and anal acoustic reflectometry measurements

Drug: Reboxetine 8 mg

Single dose placebo citalopram

PLACEBO COMPARATOR

A blinded single dose visually identical placebo pill to citalopram is administered three hours before urethral pressure reflectometry and anal acoustic reflectometry measurements

Drug: Placebo oral tablet

Single dose placebo reboxetine

PLACEBO COMPARATOR

A blinded single dose visually identical placebo pill to reboxetine is administered two hours before urethral pressure reflectometry and anal acoustic reflectometry measurements

Drug: Placebo oral tablet

Interventions

Citalopram 40mg DRUG

Single dose

Single dose citalopram

Reboxetine 8 mg DRUG

Single dose

Single dose reboxetine

Placebo oral tablet DRUG

Single dose

Also known as: Placebo to citalopram

Single dose placebo citalopram

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed written consent of participation
• Female
• Age between 18 and 55 years (both included)
• Normal weight (BMI 18,5 to 30,0 kg/m2).
• Regular use of safe contraceptive products ie. Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long acting injections) through the entire trial and until eight days after the study has ended for the subject (registered at trial day one, two and three). Subjects who are postmenopausal (defined as no menses for 12 months or more prior enrolment) can be included without use of contraceptive products.

You may not qualify if:

• Known hypersensitivity of Citalopram.
• Known hypersensitivity of Edronax.
• A history of significant cardiovascular, gastrointestinal, endocrine, hematologic, immunologic, metabolic or genitourologic disease (including pelvic surgery because of trauma, pelvic trauma, lower urinary tract surgery, irradiation to the pelvis, history or evidence of an anatomical anomaly of the lower urinary tract, urinary outlet obstruction, urinary retention, urethral hypermobility , prolapse of pelvic organs, hematuria or urinary tract infection at screening) or lung disease, neurologic, dermatologic, psychiatric disease, kidney disease, malign diseases or other major diseases assessed by the investigator.
• Known QT-interval prolongation or congenital long QT syndrome
• History or objective symptoms of urinary incontinence
• Current infectious disease (fever and symptoms associated with viral or bacterial disease (including respiratory tract infections) or fungal disease (excluding cutaneous infection).
• Pulse under 40 beats pr. minute or above 100 beats pr. minute. Average systolic blood pressure above 140 mmHg or average diastolic blood pressure over 90 mmHg (average of three measurements performed on screening). In case blood pressure or pulse should deviate from these criteria allowance of three additional measurements are accepted.
• Current participation in other clinical trials that might affect the results of this trial (judged by the investigators).
• Use of prescription drugs, over the-counter drugs or herbalism drugs. Exceptions from these criteria are use of paracetamol (4 g a day) and safe contraception as stated above.
• Current consumption of alcohol above 14 units of alcohol a week.
• Smoking within three months.
• Drug abuse within three months.
• Present pregnancy, at screening or during the trial, including a positive pregnancy test (presented at trial day one, two or three).
• Breastfeeding at screening or during the study (registered at trial day one, two and three).

Sponsors & Collaborators

• University Hospital Bispebjerg and Frederiksberg: lead

Study Sites (1)

Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital

Copenhagen, 2400, Denmark

Location

MeSH Terms

Conditions

Urinary Incontinence, Stress; Fecal Incontinence

Interventions

Citalopram; Reboxetine

Condition Hierarchy (Ancestors)

Urinary Incontinence; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Rectal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring

Study Officials

• Jesper Sonne, DMSc

  University Hospital Frederiksberg and Bispebjerg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Model Details: Single center, randomized, double-blind, placebo controlled, three period cross over phase I study

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: September 20, 2019
• Study Start: September 17, 2019
• Primary Completion: February 1, 2020
• Study Completion: May 1, 2020
• Last Updated: June 9, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)