To evaluate the effect of beta 3 adrenoreceptor agonist on urethral pressure variations during filling phase and to initially explore the possibilities for individualisation of treatment for overactive bladder symptoms.
ID
Source
Brief title
Condition
- Urethral disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Number (proportion) of patients with a reduction of significant urethral
pressure variations >15cmH2O on urodynamic investigation (two sequential
standard filling cystometries until strong desire to void) while on treatment
with beta 3 adrenoreceptor agonist.
Secondary outcome
* Difference of total number of urethral pressure variations on urodynamic
investigation after treatment, compared to initial urodynamic investigation.
* Difference in volume to first detrusor contraction between *before* and *on
treatment*.
* Differences in volume to first sensation of filling, normal desire to void
and strong desire to void, between *before* and *on treatment*.
* Difference in volume to first urethral pressure drop between *before* and *on
treatment*.
* Difference in largest pressure drop (cmH2O) between *before* and *on
treatment*.
* To explore the association of symptoms and voiding diary data before and on
treatment with a beta 3 adrenoreceptor agonist with significant urethral
pressure variations/ urethral pressure drops during urodynamic investigation
(before and on treatment).
* Sexual function as measured with a questionnaire before and on treatment with
beta 3 adrenoreceptor agonist.
Comparison of (grouped average) individual before and on treatment effect(s) of
a beta 3 adrenoreceptor agonist on symptoms and voiding diary and urodynamic
parameters
Background summary
Patients with overactive bladder symptoms have an increased voiding frequency
and a sudden need to urinate (*urinary urgency*). In a large proportion of
these patients detrusor (=bladder muscle) overactivity can be demonstrated
during the filling (urine-storage) phase of a urodynamic investigation (=
investigation to measure bladder function or dysfunction, which explains the
pathophysiology of the symptoms). With or without urodynamic diagnosis, the
mainstay of treatment for patients with overactive bladder symptoms is oral
anticholinergical or antimuscarinergical pharmacotherapy (*bladder muscle
relaxants*).
During the filling (urine storage) phase of a urodynamic investigation however,
urethral (bladder outlet) pressure variations can be observed in association
with detrusor overactivity in a proportion of patients. The clinical relevance
and or the role of urethral pressure variations in the pathophysiology are yet
not precisely established.
Recently a beta 3 adrenoreceptor agonist is approved for the treatment of
overactive bladder symptoms. The beta 3 adrenoreceptor agonist stimulates
inhibition of detrusor overactivity (and is clinically and urodynamically
effective in this regard). Theoretically beta 3 adrenoreceptor agonists may,
apart from inhibition of detrusor overactivity, stimulate the urethra to
maintain closure *contraction.
Patients with urethral pressure variations might therefore especially benefit
from beta 3 adrenoreceptor agonist since theoretically the treatment might
*stabilize* the urethral pressure and therefore reduce symptoms of *urinary
urgency*. The effect of a beta 3 adrenoreceptor agonist on the urethral
pressure and or on urethral pressure variations during filling cystometry is
however unknown.
Study objective
To evaluate the effect of beta 3 adrenoreceptor agonist on urethral pressure
variations during filling phase and to initially explore the possibilities for
individualisation of treatment for overactive bladder symptoms.
Study design
Multicentre prospective open label observational cohort study to evaluate the
short term urodynamic effect of treatment with a beta 3 adrenoreceptor agonist,
in patients with symptoms of overactive bladder.
After initial urodynamic investigation a cohort of patients will be treated for
6 weeks with beta 3 adrenoreceptor agonist to conclude with * endpoint -
urodynamic investigation while on medication. The study is an observational
cohort with invasive * endpoint- measurement.
Study burden and risks
Treatment with beta 3 adrenoreceptor agonist is clinically safe and effective.
Urodynamic testing at the start of treatment is standard in patients resistant
to first line treatment. However, also in second line treatment a pragmatic
approach on the basis of symptoms without further urodynamic tests is usually
the first step of management in many practices. The second urodynamic
investigation, and for some patients also the initial urodynamic investigation
will be extra, as a consequence of our research question.
Lijnbaan 32
Den Haag 2512 VA
NL
Lijnbaan 32
Den Haag 2512 VA
NL
Listed location countries
Age
Inclusion criteria
Female.
>18 years of age.
Mentally fit to consent.
(Referred with) Bothersome OAB symptoms (standard symptom and bother score)
Voiding diary with total urine production in 24 hour (morning to morning) <2200mL
Treating physician has indicated treatment with B3AA Mirabegron
Signed informed consent
May have had *unsatisfying- treatment with antimuscarinergic medication
Willing to stop medication for lower urinary tract dysfunction 2 days before urodynamic investigation (at entry of study)
Willing to start B3AA *study medication- after initial urodynamic investigation
Exclusion criteria
* Sediment + or clinical signs of UTI at the start of the urodynamic investigation
* Necessity to perform CIC or significant post void residual (>100mL).
* Significant voiding abnormalities; bladder outlet obstruction (UDI >grade 1 or BOOI >20) or underactive or acontractile detrusor.
* Unwilling or unable * according to treating physician- to stop current treatment for lower urinary tract dysfunction.
* Treatment with intradetrusor botulinum toxin less than one year before urodynamic investigation (whether or not symptomatically effective).
* Having a contraindication for treatment with B3AA : severe renal impairment with GFR <15 mL/min/1.73m2 or patients requiring haemodialysis) or severe hepatic impairment (Child-Pugh Class C)
* Pregnancy or breastfeeding.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL48463.098.14 |