Stress Urinary IncontinencePhase 1NCT04097288
Effects of Single Dose Citalopram and Reboxetine on Urethral and Anal Closure Function on Healthy Female Subjects
A Phase 1 study testing Citalopram 40mg and Reboxetine 8 mg in people with Stress Urinary Incontinence and Fecal Incontinence, run by University Hospital Bispebjerg and Frederiksberg at 1 site in Denmark.
Trial summary
This study will investigate if citalopram, a selective serotonin reuptake inhibitor, is reducing the opening pressure of the urethra and possibly causing or worsening stress urinary incontinence. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Stress Urinary Incontinence, Fecal Incontinence
- What is being tested?
- Citalopram 40mg and Reboxetine 8 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteDenmark
- Study dates
- 17 Sep 2019to 1 May 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Signed written consent of participation
- Female
- Age between 18 and 55 years (both included)
- Normal weight (BMI 18,5 to 30,0 kg/m2).
- Regular use of safe contraceptive products ie. Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long acting injections) through the entire trial and until eight days after the study has ended for the subject (registered at trial day one, two and three). Subjects who are postmenopausal (defined as no menses for 12 months or more prior enrolment) can be included without use of contraceptive products.
Who cannot join
- Known hypersensitivity of Citalopram.
- Known hypersensitivity of Edronax.
- A history of significant cardiovascular, gastrointestinal, endocrine, hematologic, immunologic, metabolic or genitourologic disease (including pelvic surgery because of trauma, pelvic trauma, lower urinary tract surgery, irradiation to the pelvis, history or evidence of an anatomical anomaly of the lower urinary tract, urinary outlet obstruction, urinary retention, urethral hypermobility , prolapse of pelvic organs, hematuria or urinary tract infection at screening) or lung disease, neurologic, dermatologic, psychiatric disease, kidney disease, malign diseases or other major diseases assessed by the investigator.
- Known QT-interval prolongation or congenital long QT syndrome
- History or objective symptoms of urinary incontinence
- Current infectious disease (fever and symptoms associated with viral or bacterial disease (including respiratory tract infections) or fungal disease (excluding cutaneous infection).
Show all 15Show fewer
- Pulse under 40 beats pr. minute or above 100 beats pr. minute. Average systolic blood pressure above 140 mmHg or average diastolic blood pressure over 90 mmHg (average of three measurements performed on screening). In case blood pressure or pulse should deviate from these criteria allowance of three additional measurements are accepted.
- Current participation in other clinical trials that might affect the results of this trial (judged by the investigators).
- Use of prescription drugs, over the-counter drugs or herbalism drugs. Exceptions from these criteria are use of paracetamol (4 g a day) and safe contraception as stated above.
- Current consumption of alcohol above 14 units of alcohol a week.
- Smoking within three months.
- Drug abuse within three months.
- Present pregnancy, at screening or during the trial, including a positive pregnancy test (presented at trial day one, two or three).
- Breastfeeding at screening or during the study (registered at trial day one, two and three).
- Any kind of condition (anamnestic or objective) that the investigator assess that must lead to exclusion of this study.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital
Copenhagen, 2400
About this study
This study will investigate if citalopram, a selective serotonin reuptake inhibitor, is reducing the opening pressure of the urethra and possibly causing or worsening stress urinary incontinence. Reboxetine, a norepinephrine reuptake inhibitor, is known to increase urethral opening pressure through actions on adrenoceptors in Onuf´s nucleus and will act as an active control.
Furthermore, this study is performed to explore the effects of reboxetine and citalopram on the opening pressure of the anal canal.
Read the detailed description
This study will investigate if citalopram, a selective serotonin reuptake inhibitor, is reducing the opening pressure of the urethra and possibly causing or worsening stress urinary incontinence. Theoretically, citalopram can affect the tone of urethra through actions on serotonergic receptors in Onuf´s nucleus that innervates the striated muscle in urethra. Treatment with selective serotonin reuptake inhibitors is common and has been associated with urinary incontinence. Stress urinary incontinence is frequent and the most common cause of urinary incontinence. Reboxetine, a norepinephrine reuptake inhibitor, is known to increase urethral opening pressure through actions on adrenoceptors in Onuf´s nucleus and will act as an active control. Should the tone of urethra decrease significantly after ingestion of citalopram, this study would contribute to a deeper understanding of stress urinary incontinence and give rise to a debate of pharmacologic treatment of stress urinary incontinence diagnosed in patients treated with citalopram (this debate may also include use of selective serotonin reuptake inhibitor).
Furthermore, this study is performed to explore the effects of reboxetine and citalopram on the opening pressure of the anal canal. Onuf´s nucleus, like the striated urethral sphincter, innervates the striated skeletal muscle of the external sphincter in the anal canal. The prevalence of fecal incontinence (FI) increases with age and is estimated to affect 15% of people aged over 50 years. Pharmacologic treatment of fecal incontinence is very sparse and new treatments it is very desirable. If reboxetine or citalopram increases the anal opening pressure these pharmacologic agents might leads to new ways of treating FI, making this study the first to explore this area.
The design is a single center, randomized, double-blind, placebo controlled, three period cross over phase I study. Twenty-four healthy, female subjects are recruited and investigated during three independent trial days where one of the pharmacologic agents is given each trial day (citalopram, reboxetine or placebo) in concordance with the sequence (order of the pharmacologic agents given). Subjects will be drafted randomly and evenly among the three sequences possible. During all trial days pressures of the urethra and the anal canal of every subject will be measured by urethral pressure reflectometry and anal acoustic reflectometry at the time of maximum plasma concentration of citalopram and reboxetine. A clinically meaningful difference in urethral pressure after administration of citalopram is assessed to be 10 cmH2O compared to placebo (reboxetine acts as an active control) while a clinically meaningful difference in anal pressure after administration of citalopram or reboxetine is assessed to be 15 cmH2O compared to placebo.
- Conditions
- Stress Urinary Incontinence, Fecal Incontinence
- Being tested
- Citalopram 40mg, Reboxetine 8 mg, Placebo oral tablet
- Keywords
- stress urinary incontinence, pharmacologic treatment, fecal incontinence
- Medical subject headings
- Urinary Incontinence, Stress, Fecal Incontinence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Citalopram 40mgDrug
Single dose
Reboxetine 8 mgDrug
Single dose
Placebo oral tabletDrug
Also called Placebo to citalopram
Single dose
Placebo oral tabletDrug
Also called Placebo tó reboxetine
Single dose
| Study group | Role | What they receive |
|---|---|---|
| Single dose citalopram | Experimental | A blinded single dose 40 mg citalopram is administered three hours before urethral pressure reflectometry and anal acoustic reflectometry measurements Receives: Drug: Citalopram 40mg |
| Single dose reboxetine | Active comparator | A blinded single dose 8 mg reboxetine is administered two hours before urethral pressure reflectometry and anal acoustic reflectometry measurements Receives: Drug: Reboxetine 8 mg |
| Single dose placebo citalopram | Placebo comparator | A blinded single dose visually identical placebo pill to citalopram is administered three hours before urethral pressure reflectometry and anal acoustic reflectometry measurements Receives: Drug: Placebo oral tablet |
| Single dose placebo reboxetine | Placebo comparator | A blinded single dose visually identical placebo pill to reboxetine is administered two hours before urethral pressure reflectometry and anal acoustic reflectometry measurements Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in average UOP-placebo and average UOP-citalopram (during relaxation)
Difference in urethral opening pressure
Measured: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine
Difference in average AOP-placebo and average AOP-citalopram or average AOP-reboxetine (during relaxation)
Difference in urethral opening pressure
Measured: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine
Secondary outcomes (3)
Difference in average UOP-placebo and average UOP-reboxetine (during relaxation)
Difference in urethral opening pressure
Measured: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine
Difference in average UOP-placebo and average UOP-citalopram or UOP-reboxetine (during voluntary contraction)
Difference in urethral opening pressure
Measured: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine
Difference in average AOP-placebo and average AOP-citalopram or AOP-reboxetine (during voluntary contraction).
Difference in urethral opening pressure
Measured: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2019
- Study start17 Sep 2019
- Primary completion1 Feb 2020
- Study completion1 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stress Urinary IncontinenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Single center, randomized, double-blind, placebo controlled, three period cross over phase I study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Bispebjerg and Frederiksberg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thea Christoffersen, University Hospital Bispebjerg and Frederiksberg
- Investigators
- Jesper Sonne, DMSc, Principal investigator, University Hospital Frederiksberg and Bispebjerg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04097288
- Sponsor's protocol ID
- SSRI-UPR-01
- Other IDs
- 2019-000059-14, 2019
- Status last verified
- Jun 2021
- First submitted
- 21 May 2019
- Last updated
- 9 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Christoffersen T, Riis T, Sonne J, Kornholt J, Sonne DP, Klarskov N. Effect of reboxetine and citalopram on anal opening pressure in healthy women: A randomized, double-blind, placebo-controlled crossover study. Neurogastroenterol Motil. 2024 Oct;36(10):e14882. doi: 10.1111/nmo.14882. Epub 2024 Jul 30.
PubMed 39076155
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Single Dose Citalopram and Reboxetine on Urethral and Anal Closure Function on Healthy Female Subjects
- ClinicalTrials.gov ID
- NCT04097288
- Acronym / sponsor ID
- SSRI-UPR-01
- Conditions
- Stress Urinary Incontinence, Fecal Incontinence
- Keywords
- stress urinary incontinence, pharmacologic treatment, fecal incontinence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Hospital Bispebjerg and FrederiksbergUniversity, hospital or other
- Study start
- 17 Sep 2019 (actual)
- Primary completion
- 1 Feb 2020 (actual)
- Study completion
- 1 May 2020 (actual)
- First posted
- 20 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate if citalopram, a selective serotonin reuptake inhibitor, is reducing the opening pressure of the urethra and possibly causing or worsening stress urinary incontinence. Reboxetine, a norepinephrine reuptake inhibitor, is known to increase urethral opening pressure through actions on adrenoceptors in Onuf´s nucleus and will act as an active control.
Furthermore, this study is performed to explore the effects of reboxetine and citalopram on the opening pressure of the anal canal.
Detailed description
This study will investigate if citalopram, a selective serotonin reuptake inhibitor, is reducing the opening pressure of the urethra and possibly causing or worsening stress urinary incontinence. Theoretically, citalopram can affect the tone of urethra through actions on serotonergic receptors in Onuf´s nucleus that innervates the striated muscle in urethra. Treatment with selective serotonin reuptake inhibitors is common and has been associated with urinary incontinence. Stress urinary incontinence is frequent and the most common cause of urinary incontinence. Reboxetine, a norepinephrine reuptake inhibitor, is known to increase urethral opening pressure through actions on adrenoceptors in Onuf´s nucleus and will act as an active control. Should the tone of urethra decrease significantly after ingestion of citalopram, this study would contribute to a deeper understanding of stress urinary incontinence and give rise to a debate of pharmacologic treatment of stress urinary incontinence diagnosed in patients treated with citalopram (this debate may also include use of selective serotonin reuptake inhibitor).
Furthermore, this study is performed to explore the effects of reboxetine and citalopram on the opening pressure of the anal canal. Onuf´s nucleus, like the striated urethral sphincter, innervates the striated skeletal muscle of the external sphincter in the anal canal. The prevalence of fecal incontinence (FI) increases with age and is estimated to affect 15% of people aged over 50 years. Pharmacologic treatment of fecal incontinence is very sparse and new treatments it is very desirable. If reboxetine or citalopram increases the anal opening pressure these pharmacologic agents might leads to new ways of treating FI, making this study the first to explore this area.
The design is a single center, randomized, double-blind, placebo controlled, three period cross over phase I study. Twenty-four healthy, female subjects are recruited and investigated during three independent trial days where one of the pharmacologic agents is given each trial day (citalopram, reboxetine or placebo) in concordance with the sequence (order of the pharmacologic agents given). Subjects will be drafted randomly and evenly among the three sequences possible. During all trial days pressures of the urethra and the anal canal of every subject will be measured by urethral pressure reflectometry and anal acoustic reflectometry at the time of maximum plasma concentration of citalopram and reboxetine. A clinically meaningful difference in urethral pressure after administration of citalopram is assessed to be 10 cmH2O compared to placebo (reboxetine acts as an active control) while a clinically meaningful difference in anal pressure after administration of citalopram or reboxetine is assessed to be 15 cmH2O compared to placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Single center, randomized, double-blind, placebo controlled, three period cross over phase I study
| Arm | Type | Receives |
|---|---|---|
| Single dose citalopram | Experimental | Drug: Citalopram 40mgA blinded single dose 40 mg citalopram is administered three hours before urethral pressure reflectometry and anal acoustic reflectometry measurements |
| Single dose reboxetine | Active comparator | Drug: Reboxetine 8 mgA blinded single dose 8 mg reboxetine is administered two hours before urethral pressure reflectometry and anal acoustic reflectometry measurements |
| Single dose placebo citalopram | Placebo comparator | Drug: Placebo oral tabletA blinded single dose visually identical placebo pill to citalopram is administered three hours before urethral pressure reflectometry and anal acoustic reflectometry measurements |
| Single dose placebo reboxetine | Placebo comparator | Drug: Placebo oral tabletA blinded single dose visually identical placebo pill to reboxetine is administered two hours before urethral pressure reflectometry and anal acoustic reflectometry measurements |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Signed written consent of participation
- Female
- Age between 18 and 55 years (both included)
- Normal weight (BMI 18,5 to 30,0 kg/m2).
- Regular use of safe contraceptive products ie. Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long acting injections) through the entire trial and until eight days after the study has ended for the subject (registered at trial day one, two and three). Subjects who are postmenopausal (defined as no menses for 12 months or more prior enrolment) can be included without use of contraceptive products.
Key exclusion criteria (15 listed)
- Known hypersensitivity of Citalopram.
- Known hypersensitivity of Edronax.
- A history of significant cardiovascular, gastrointestinal, endocrine, hematologic, immunologic, metabolic or genitourologic disease (including pelvic surgery because of trauma, pelvic trauma, lower urinary tract surgery, irradiation to the pelvis, history or evidence of an anatomical anomaly of the lower urinary tract, urinary outlet obstruction, urinary retention, urethral hypermobility , prolapse of pelvic organs, hematuria or urinary tract infection at screening) or lung disease, neurologic, dermatologic, psychiatric disease, kidney disease, malign diseases or other major diseases assessed by the investigator.
- Known QT-interval prolongation or congenital long QT syndrome
- History or objective symptoms of urinary incontinence
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Citalopram 40mgSingle dose | Drug | Single dose citalopram |
| Reboxetine 8 mgSingle dose | Drug | Single dose reboxetine |
| Placebo oral tabletAlso: Placebo to citalopramSingle dose | Drug | Single dose placebo citalopram |
| Placebo oral tabletAlso: Placebo tó reboxetineSingle dose | Drug | Single dose placebo reboxetine |
Primary outcome
Difference in average UOP-placebo and average UOP-citalopram (during relaxation)
Time frame: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine
Difference in urethral opening pressure
Difference in average AOP-placebo and average AOP-citalopram or average AOP-reboxetine (during relaxation)
Time frame: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine
Difference in urethral opening pressure
3 secondary outcomes
Difference in average UOP-placebo and average UOP-reboxetine (during relaxation)
Time frame: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine
Difference in average UOP-placebo and average UOP-citalopram or UOP-reboxetine (during voluntary contraction)
Time frame: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine
Difference in average AOP-placebo and average AOP-citalopram or AOP-reboxetine (during voluntary contraction).
Time frame: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2021.
- Derived from this study: PubMed 39076155Christoffersen T, Riis T, Sonne J, Kornholt J, Sonne DP, Klarskov N. Effect of reboxetine and citalopram on anal opening pressure in healthy women: A randomized, double-blind, placebo-controlled crossover study. Neurogastroenterol Motil. 2024 Oct;36(10):e14882. doi: 10.1111/nmo.14882. Epub 2024 Jul 30.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jesper Sonne, DMSc principal investigator
University Hospital Frederiksberg and Bispebjerg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Citalopram 40mg and Reboxetine 8 mg in people with Stress Urinary Incontinence and Fecal Incontinence, run by University Hospital Bispebjerg and Frederiksberg at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in average UOP-placebo and average UOP-citalopram (during relaxation) (time frame: UPR measurements are performed 3 hours after blinded administration of citalopram or placebo to citalopram and two hours after blinded administration of reboxetine/placebo to reboxetine). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04097288, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2021.