Clinical trial NCT05188742: Sequencing and Combination of Mirabegron and TTNS in Overactive Bladder Syndrome: a Multicenter, Randomized, Open-label, Crossover Trial
Official title: Sequencing and Combination of Mirabegron and Transcutaneous Tibial Nerve Stimulation (TTNS) in Overactive Bladder Syndrome: a Multicenter, Randomized, Open-label, Crossover Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Overactive Bladder Syndrome
Keywords: overactive bladder
mirabegron
transcutaneous tibial nerve stimulation
Lead sponsor: Taipei Veterans General Hospital, Taiwan
Sponsor class: OTHER_GOV
First posted: 2022-01-12
Enrollment: 180
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Treatment sequence: randomized with 1:1 ratio to either Sequence A or Sequence B Sequence A: mirabegron 50mg monotherapy x 8 weeks -\> multi-modal combination treatment x 4 weeks -\> TTNS monotherapy x 8 weeks Sequence B: TTNS monotherapy x 8 weeks -\> multi-modal combination treatment x 4 weeks -\> mirabegron 50mg monotherapy x 8 weeks
Primary purpose: TREATMENT

Brief summary: Research question:

A wealth of existing research has established the independent effectiveness of mirabegron and neuromodulation in the treatment of overactive bladder syndrome. Optimizing the use of these effective and well-tolerated treatment modalities is an important clinical goal and warrants further research. The primary aim of this trial is to answer the questions: how does varying the treatment sequence involving mirabegron and transcutaneous tibial nerve stimulation (TTNS) affect efficacy and patient acceptance and what is the second-line efficacy of either treatment modality?

Primary objective:

To evaluate improvement in storage symptoms, as measured by changes in Overactive Bladder Symptom Score (OABSS), International Prostate Symptom Score (IPSS) and parameters of voiding diary, in overactive bladder (OAB) patients receiving mirabegron or TTNS as first-line therapy when crossed over to second-line therapy with the opposite treatment modality

Secondary objectives:

To evaluate improvement in symptoms, as measured by changes in OABSS, IPSS and parameters of voiding diary, on first-line therapy with mirabegron or TTNS followed by combination multi-modal therapy To evaluate the effect of multi-modal treatment approach on patient's perception of treatment satisfaction and symptom control To evaluate urodynamic profiles of patients treated with multi-modal approach

Detailed description: Study design: Prospective, randomized, multicenter, open-label, cross-over trial Treatment sequence: randomized with 1:1 ratio to either Sequence A or Sequence B

Sequence A: mirabegron 50mg monotherapy x 8 weeks -\> multi-modal combination treatment x 4 weeks -\> TTNS monotherapy x 8 weeks Sequence B: TTNS monotherapy x 8 weeks -\> multi-modal combination treatment x 4 weeks -\> mirabegron 50mg monotherapy x 8 weeks

Patient population: adults ≥ 20 years who have experienced symptoms of OAB, as defined by International Continence Society (ICS) diagnostic criteria, for at least 3 months

Sample size: approximately 180 patients

Eligibility criteria: Inclusion Criteria:

* Adult OAB patients ≥20 years
* Diagnosed with moderate to severe OAB (with or without urgency incontinence) based on OABSS \>5 and clinical assessment, with UUI-predominant presentation, for at least 3 months
* Able to receive TTNS and accommodate treatment logistics (30 min per on-site session, twice weekly)
* Provided informed consent to participate in the study

Exclusion Criteria:

* Neurologic conditions associated with OAB symptoms
* History of stress urinary incontinence
* Use of intravesical onabotulinumoxinA within recent 6 months
* Postvoid residual urine volume (PVR) ≥ 100mL
* Evidence of active urinary tract infection or urinary tract stone at screening
* Genitourinary tract operation during the 3-month period prior to baseline
* Confirmed or suspected genitourinary tract or pelvic malignancy
* History of uncontrolled hypertension (systolic \>160 mmHg and/or diastolic \>110 mmHg)
* History of intolerance to mirabegron
* Patients with pacemakers or implantable defibrillators
* Patients prone to excessive bleeding
* Patients with nerve damage that could impact percutaneous tibial nerve or pelvic floor function
* Patients who are pregnant or planning to become pregnant during the duration of treatment
* History of medical conditions or presence of patient factors that, in the judgement of the investigator, would preclude adherence to study protocol

Primary outcomes:
measure: Changes from baseline to end of treatment (EoT) (Week 20) in OABSS
timeFrame: Baseline and Week 20
Secondary outcomes:
measure: Changes from baseline to Week 12 in OABSS
timeFrame: Baseline and Week 12
measure: Changes from baseline to Week 12 and 20/end of treatment (EoT) in IPSS
timeFrame: Baseline, and Week 12 and 20
measure: Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Micturitions per 24 Hours
timeFrame: Baseline, and Week 12 and 20
measure: Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Nocturia Episodes per 24 Hours
timeFrame: Baseline, and Week 12 and 20
measure: Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Urgency Episodes per 24 Hours
timeFrame: Baseline, and Week 12 and 20
measure: Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Urgency Incontinence Episodes per 24 Hours
timeFrame: Baseline, and Week 12 and 20
measure: Changes from Week 8 to Week 20 in OABSS
timeFrame: Week 8 to Week 20
measure: Changes from Week 8 to Week 20 in IPSS
timeFrame: Week 8 to Week 20
measure: Changes from Week 8 to Week 20 in Mean Number of Micturitions per 24 Hours
timeFrame: Week 8 to Week 20
measure: Changes from Week 8 to Week 20 in Mean Number of Nocturia Episodes per 24 Hours
timeFrame: Week 8 to Week 20
measure: Changes from Week 8 to Week 20 in Mean Number of Urgency Episodes per 24 Hours
timeFrame: Week 8 to Week 20
measure: Changes from Week 8 to Week 20 in Mean Number of Urgency Incontinence Episodes per 24 Hours
timeFrame: Week 8 to Week 20
measure: Changes from Week 12 to Week 20 in OABSS
timeFrame: Week 12 to Week 20
measure: Changes from Week 12 to Week 20 in IPSS
timeFrame: Week 12 to Week 20
measure: Changes from Week 12 to Week 20 in Mean Number of Micturitions per 24 Hours
timeFrame: Week 12 to Week 20
measure: Changes from Week 12 to Week 20 in Mean Number of Nocturia Episodes per 24 Hours
timeFrame: Week 12 to Week 20
measure: Changes from Week 12 to Week 20 in Mean Number of Urgency Episodes per 24 Hours
timeFrame: Week 12 to Week 20
measure: Changes from Week 12 to Week 20 in Mean Number of Urgency Incontinence Episodes per 24 Hours
timeFrame: Week 12 to Week 20
measure: Changes from baseline to Week 12 and 20/end of treatment (EoT) in Overactive Bladder Questionnaire-Short Form (OAB-Q-SF) score
timeFrame: Baseline, and Week 12 and 20
measure: Changes from baseline to Week 12 and 20/end of treatment (EoT) in Bladder Assessment Tool (BAT) score
timeFrame: Baseline, and Week 12 and 20
measure: Changes from baseline to Week 12 and 20/end of treatment (EoT) in Treatment Satisfaction-Visual Analog Scale (TS-VAS) score
timeFrame: Baseline, and Week 12 and 20
Other outcomes:
Locations:
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Taipei Veterans General Hospital, Taiwan
name: Chih-Chieh Lin, MD/Phd
role: PRINCIPAL_INVESTIGATOR
References: