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

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)

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.

Study Overview

• Status: Completed
• Conditions: Urinary Incontinence, Stress; Fecal Incontinence
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Imipramine Hydrochloride 25 MG

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen NV
    • Copenhagen, Copenhagen NV, Denmark, 2400
      • Zelo Phase I Unit, Dept. of Clinical Pharmacology, Bispebjerg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Jonatan Kornholt
• Investigators: Principal Investigator: Jonatan Kornholt, MD, Klinisk farmakologisk afdeling, Bispebjerg Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2017
• Primary Completion (Actual): June 16, 2017
• Study Completion (Actual): June 21, 2017

Study Registration Dates

• First Submitted: March 20, 2017
• First Submitted That Met QC Criteria: March 30, 2017
• First Posted (Actual): April 6, 2017

Study Record Updates

• Last Update Posted (Actual): February 12, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Gastrointestinal Diseases; Urination Disorders; Intestinal Diseases; Rectal Diseases; Urinary Incontinence; Urinary Incontinence, Stress; Fecal Incontinence; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Imipramine
• Other Study ID Numbers: TCA-UPR-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No