Effects of Single Dose Citalopram and Reboxetine on Urethral and Anal Closure Function on Healthy Female Subjects
Condition: Stress Urinary Incontinence; Fecal Incontinence
MeSH terms: Fecal Incontinence; Urinary Incontinence; Enuresis; Urinary Incontinence, Stress
Study type: Interventional
Phase: Phase 1

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. 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.
    

Intervention name(s): Citalopram 40mg; Reboxetine 8 mg; Placebo oral tablet; Placebo oral tablet
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Single dose; Single dose; Single dose; Single dose
Other intervention name(s): Placebo to citalopram; Placebo tó reboxetine
Intervention MeSH terms: Dexetimide; Citalopram; Reboxetine; Escitalopram
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Single center, randomized, double-blind, placebo controlled, three period cross over phase I study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: stress urinary incontinence; pharmacologic treatment; fecal incontinence