Does Single Dose Imipramine Affect the Opening Pressure of the Urethral and Anal Sphincter?

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Urinary Incontinence, Stress, Fecal Incontinence

Intervention / Treatment
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* Drug: Placebo Oral Tablet
* Drug: Imipramine Hydrochloride 25 MG


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imipramine first<br>A: Imipramine Hydrochloride 25 MG x2 B: Placebo Oral Tablet x2 | Drug: Placebo Oral Tablet<br>* Placebo film coated tablet: Lactose monohydrate, potato starch, gelatine, magnesium stearate, talc<br>Drug: Imipramine Hydrochloride 25 MG<br>* Two Imipramin DAK film coated tablets 25 mg each, single dose<br>* Other names: Imipramin DAK;|
| Experimental: Placebo first<br>A: Placebo Oral Tablet x2 B: Imipramine Hydrochloride 25 MG x2 | Drug: Placebo Oral Tablet<br>* Placebo film coated tablet: Lactose monohydrate, potato starch, gelatine, magnesium stearate, talc<br>Drug: Imipramine Hydrochloride 25 MG<br>* Two Imipramin DAK film coated tablets 25 mg each, single dose<br>* Other names: Imipramin DAK;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urethral Opening Pressure (UOP) | Mean change in UOP (baseline and 1 hour after drug administration). Measured with Urethral Pressure Reflectometry (UPR). | Immediately before drug/placebo administration (baseline) and 1 hour after drug/placebo administration on both study days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anal Opening Pressure (AOP) | Mean change in AOP (baseline and 1 hour after drug administration). Measured with Anal Acoustic Reflectometry (AAR). | Immediately before drug/placebo administration (baseline) and 1 hour after drug/placebo administration on both study days. |