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

• Sponsor: Jonatan Kornholt (Other)
• Overall Status: Completed
• CT.gov ID: NCT03102645
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Actual Duration (Months): 1.2
• Patients Per Site Per Month: 13.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Urinary Incontinence, Stress; Fecal Incontinence	Drug: Placebo Oral Tablet; Drug: Imipramine Hydrochloride 25 MG	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• 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.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.
• Primary Purpose: Basic Science
• 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)
• Actual Study Start Date: May 16, 2017
• Actual Primary Completion Date: Jun 16, 2017
• Actual Study Completion Date: Jun 21, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Female
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Zelo Phase I Unit, Dept. of Clinical Pharmacology, Bispebjerg Hospital	Copenhagen	Copenhagen NV	Denmark	2400

Sponsors and Collaborators

• Jonatan Kornholt

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 26, 2019

More Information

Publications

None provided.

• Responsible Party: Jonatan Kornholt, Resident doctor in the Department of Clinical Pharmacology, Bispebjerg Hospital
• ClinicalTrials.gov Identifier: NCT03102645
• Other Study ID Numbers: TCA-UPR-0001
• First Posted: Apr 6, 2017
• Last Update Posted: Feb 12, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Fecal Incontinence; Urinary Incontinence; Urinary Incontinence, Stress; Imipramine

Study Results

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 Detail	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.

Arm/Group Title	Imipramine First	Placebo First
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Imipramine First	Placebo First	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	8	8	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	16 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	8 100%	8 100%	16 100%
Male	0 0%	0 0%	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Denmark	8 100%	8 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Urethral Opening Pressure (UOP)
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imipramine	Placebo
Arm/Group Description	Imipramine Hydrochloride 25 MG: Two Imipramin DAK film coated tablets 25 mg each, single dose.	Placebo Oral Tablet: Placebo film coated tablet: Lactose monohydrate, potato starch, gelatine, magnesium stearate, talc
Measure Participants	16	16
Mean (Standard Deviation) [cmH2O]	2.90411 (13.24729)	-3.623431 (8.279883)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Imipramine, Placebo
	Comments	CROS test
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	t-test, 2 sided
	Comments	CROS. DF=14.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.5
	Confidence Interval	(2-Sided) 95%; -0.5 to 13.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Anal Opening Pressure (AOP)
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imipramine	Placebo
Arm/Group Description	Imipramine Hydrochloride 25 MG: Two Imipramin DAK film coated tablets 25 mg each, single dose.	Placebo Oral Tablet: Placebo film coated tablet: Lactose monohydrate, potato starch, gelatine, magnesium stearate, talc.
Measure Participants	16	16
Mean (Standard Deviation) [cmH2O]	12.11873 (15.79818)	-2.989054 (16.40355)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Imipramine, Placebo
	Comments	CROS test
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	t-test, 2 sided
	Comments	CROS test
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.2
	Confidence Interval	(2-Sided) 95%; 2.0 to 28.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From study day 1 to 5 days after 2nd study day.
Arm/Group Title	Imipramine		Placebo
Arm/Group Description	Imipramine Hydrochloride 25 MG x2: Two Imipramin DAK film coated tablets 25 mg each, single dose		Placebo Oral Tablet x2: Two placebo film coated tablets containing lactose monohydrate, potato starch, gelatine, magnesium stearate, and talc
All Cause Mortality
	Imipramine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Serious Adverse Events
	Imipramine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Imipramine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/16 (43.8%)		1/16 (6.3%)
Gastrointestinal disorders
Stomach cramps	0/16 (0%)	0	1/16 (6.3%)	1
Dry mouth	3/16 (18.8%)	3	0/16 (0%)	0
General disorders
Tired	5/16 (31.3%)	5	0/16 (0%)	0
Nervous system disorders
Dizzy	3/16 (18.8%)	3	0/16 (0%)	0
Migraine	1/16 (6.3%)	1	0/16 (0%)	0
Headache	1/16 (6.3%)	1	0/16 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.