Fecal Incontinence, Urinary Incontinence, Stress
Conditions
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.
Interventions
DRUGPlacebo Oral Tablet
Placebo film coated tablet: Lactose monohydrate, potato starch, gelatine, magnesium stearate, talc
DRUGImipramine Hydrochloride 25 MG
Two Imipramin DAK film coated tablets 25 mg each, single dose
Sponsors
Jonatan Kornholt
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, 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.
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urethral Opening Pressure (UOP) | Immediately before drug/placebo administration (baseline) and 1 hour after drug/placebo administration on both study days. | Mean change in UOP (baseline and 1 hour after drug administration). Measured with Urethral Pressure Reflectometry (UPR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anal Opening Pressure (AOP) | Immediately before drug/placebo administration (baseline) and 1 hour after drug/placebo administration on both study days. | Mean change in AOP (baseline and 1 hour after drug administration). Measured with Anal Acoustic Reflectometry (AAR). |
Countries
Denmark
Participant flow
Recruitment details
Subjects were included from 16 May 2017 to 31 May 2017 and the study days was conducted from 17 May 2017 to 16 June 2017 and the last followup call to detect adverse effects was 21 June 2017.
Pre-assignment details
Randomization determining order of arms after enrollment. At least 1 week wash out between study days. Followup 5 days after last study day to collect adverse events.
Participants by arm
| Arm | Count |
|---|---|
| Imipramine First A: Imipramine Hydrochloride 25 MG x2 B: Placebo Oral Tablet x2
Placebo Oral Tablet: Placebo film coated tablet: Lactose monohydrate, potato starch, gelatine, magnesium stearate, talc
Imipramine Hydrochloride 25 MG: Two Imipramin DAK film coated tablets 25 mg each, single dose | 8 |
| Placebo First A: Placebo Oral Tablet x2 B: Imipramine Hydrochloride 25 MG x2
Placebo Oral Tablet: Placebo film coated tablet: Lactose monohydrate, potato starch, gelatine, magnesium stearate, talc
Imipramine Hydrochloride 25 MG: Two Imipramin DAK film coated tablets 25 mg each, single dose | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Placebo First | Total | Imipramine First |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 16 Participants | 8 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Denmark | 8 participants | 16 participants | 8 participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 7 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Urethral Opening Pressure (UOP)
Mean change in UOP (baseline and 1 hour after drug administration). Measured with Urethral Pressure Reflectometry (UPR).
Time frame: Immediately before drug/placebo administration (baseline) and 1 hour after drug/placebo administration on both study days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imipramine | Urethral Opening Pressure (UOP) | 2.90411 cmH2O | Standard Deviation 13.24729 |
| Placebo | Urethral Opening Pressure (UOP) | -3.623431 cmH2O | Standard Deviation 8.279883 |
Comparison: CROS testp-value: 0.0795% CI: [-0.5, 13.5]t-test, 2 sided
Secondary
Anal Opening Pressure (AOP)
Mean change in AOP (baseline and 1 hour after drug administration). Measured with Anal Acoustic Reflectometry (AAR).
Time frame: Immediately before drug/placebo administration (baseline) and 1 hour after drug/placebo administration on both study days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Imipramine | Anal Opening Pressure (AOP) | 12.11873 cmH2O | Standard Deviation 15.79818 |
| Placebo | Anal Opening Pressure (AOP) | -2.989054 cmH2O | Standard Deviation 16.40355 |
Comparison: CROS testp-value: 0.0395% CI: [2, 28.2]t-test, 2 sided