Does Single Dose Imipramine Affect the Opening Pressure of the Urethral and Anal Sphincter?
Condition: Urinary Incontinence, Stress; Fecal Incontinence
MeSH terms: Fecal Incontinence; Urinary Incontinence; Urinary Incontinence, Stress
Intervention: Placebo Oral Tablet; Imipramine Hydrochloride 25 MG
Intervention description: Placebo film coated tablet: Lactose monohydrate, potato starch, gelatine, magnesium stearate, talc; Two Imipramin DAK film coated tablets 25 mg each, single dose
Intervention MeSH terms: Imipramine
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
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.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: Packaging, randomization and masking of investigational drugs (imipramine and placebo) by Region Hovedstadens Apothecary before delivery to investigator. Sealed envelope with participant ID and drug data will be opened after data analysis.
Enrollment: 16.0
Sex: Female
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

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.