Clinical trial NCT03102645: Does Single Dose Imipramine Affect the Opening Pressure of the Urethral and Anal Sphincter?
Official title: Effect of Single Dose Imipramine on the Urethral and Anal Sphincter in Healthy Women Measured With Urethral Pressure Reflectometry (UPR) and Anal Acoustic Reflectometry (AAR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Urinary Incontinence, Stress
Fecal Incontinence
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
First posted: 2017-04-06
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 16 healthy female subjects. Double-blinded, crossover study on two days with 1 week washout. Either placebo or imipramine 50 mg single dose before and after measurement of UOP and AOP.
Primary purpose: BASIC_SCIENCE

Brief summary: A double-blinded, randomized, crossover study in healthy females with placebo and single dose imipramine 50 mg.

Primary objective: Does imipramine increase the tone of the external urethral sphincter? Urethral Opening Pressure (UOP) is measured with Urethral Pressure Reflectometry (UPR). UOP increases correlate with effect in treating stress urinary incontinence. Can imipramine treat stress urinary incontinence? Secondary objective: Does imipramine increase the tone of the anal sphincter? The opening pressure is measured with Anal Acoustic Reflectometry (AAR). The investigators also wish to establish the within-subject standard deviation for AAR to enable power calculations in future studies.


Eligibility criteria: Inclusion Criteria:

* Signed consent form.
* Healthy.
* Female.
* Non-smoker.
* Age 18 to 55, both inclusive.
* Normal weight: BMI 19.5 to 30.0 kg/m2. Weight minimum 50 kg.
* No breastfeeding.
* No pregnancy during the study.
* No other clinical trials during the study.

Exclusion Criteria:

* Known allergy to imipramine or any of the other known constituents.
* Medical history with significant cardiovascular, gastrointestinal, endocrinologic, hematologic, immunologic, metabolic, genitourologic, dermatologic, psychiatric, neurologic or dermatologic disease, lung disease, kidney disease, malignant disease or other significant diseases as assessed by the investigator.
* Medical history of urinary incontinence.
* Infectious disease 1 week prior to study day 1 or study day 2.
* Clinically significant findings during the physical examination.
* Pregnancy.
* Heart rate \< 40 or \> 100 beats per minute. Mean systolic blood pressure \> 140 mmHg or mean diastolic blood pressure \> 90 mmHg (mean of the measures on the screening day).
* Prescription, over the counter or herbal medication two weeks prior to study day 1 or study day 2. Excluding paracetamol and excluding oral contraceptives.
* Smoking 3 months prior to study day 1 or study day 2.
* Alcohol abuse, meaning \> 14 units (12 g alcohol) per week within three weeks prior to study day 1 or study day 2.
* Drug abuse 3 months prior to study day 1 or study day 2.
* Any condition as assessed by the investigator.

Primary outcomes:
measure: Urethral Opening Pressure (UOP)
timeFrame: Immediately before drug/placebo administration (baseline) and 1 hour after drug/placebo administration on both study days.
Secondary outcomes:
measure: Anal Opening Pressure (AOP)
timeFrame: Immediately before drug/placebo administration (baseline) and 1 hour after drug/placebo administration on both study days.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Zelo Phase I Unit, Dept. of Clinical Pharmacology, Bispebjerg Hospital
state: Copenhagen NV
Study officials:
affiliation: Klinisk farmakologisk afdeling, Bispebjerg Hospital
name: Jonatan Kornholt, MD
role: PRINCIPAL_INVESTIGATOR
References: