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Sequencing and Combination of Mirabegron and TTNS in Overactive Bladder Syndrome: a Multicenter, Randomized, Open-label, Crossover Trial

Primary Purpose

Overactive Bladder Syndrome

Status
Recruiting
Phase
Phase 4
Locations
Taiwan
Study Type
Interventional
Intervention
mirabegron
TTNS
Sponsored by
Taipei Veterans General Hospital, Taiwan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Overactive Bladder Syndrome focused on measuring overactive bladder, mirabegron, transcutaneous tibial nerve stimulation

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Taipei Veterans General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Sequence A

Sequence B

Arm Description

mirabegron 50mg OD x 8 weeks, followed by mirabegron 50mg OD and TTNS for 4 weeks, followed by TTNS twice a week x 8 weeks

TTNS twice a week x 8 weeks, followed by mirabegron 50mg OD and TTNS for 4 weeks, followed by mirabegron 50mg OD x 8 weeks

Outcomes

Primary Outcome Measures

Changes from baseline to end of treatment (EoT) (Week 20) in OABSS
Changes from baseline to Week 20 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS score represents a better outcome). Symptom improvement is defined as OABSS total score decreased by ≥ 3 points at EoT

Secondary Outcome Measures

Changes from baseline to Week 12 in OABSS
Changes from baseline to Week 12 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS score represents a better outcome)
Changes from baseline to Week 12 and 20/end of treatment (EoT) in IPSS
Changes from baseline in IPSS (International Prostate Symptom Score) at Week 12 and 20 (a lower IPSS represents a better outcome)
Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Micturitions per 24 Hours
The average number of micturitions (urinations) per 24 hours is derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a micturition diary for 3-days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Nocturia Episodes per 24 Hours
Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinates (excluding incontinence only episodes) during sleeping time per day is derived from a micturition diary in which a patient records for 3 days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Urgency Episodes per 24 Hours
The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) is derived from episodes reocrded by the patient in a micturition diary in which a patient completes for 3 days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Urgency Incontinence Episodes per 24 Hours
The involuntary leakage of urine accompanied or immediately proceeded by urgency, derived from the number of incontinence episodes recorded by the patient in a micturition diary in which a patient completes for 3 days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
Changes from Week 8 to Week 20 in OABSS
Changes from Week 8 to Week 20 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS represents a better outcome)
Changes from Week 8 to Week 20 in IPSS
Changes from Week 8 to Week 20 in IPSS (International Prostate Symptom Score) (a lower IPSS represents a better outcome)
Changes from Week 8 to Week 20 in Mean Number of Micturitions per 24 Hours
The average number of micturitions (urinations) per 24 hours is derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a 3-day micturition diary.
Changes from Week 8 to Week 20 in Mean Number of Nocturia Episodes per 24 Hours
Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinates (excluding incontinence only episodes) during sleeping time per day is derived from the 3-day patient micturition diary.
Changes from Week 8 to Week 20 in Mean Number of Urgency Episodes per 24 Hours
The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) derived from episodes recorded by the patient in a 3-day micturition diary
Changes from Week 8 to Week 20 in Mean Number of Urgency Incontinence Episodes per 24 Hours
The involuntary leakage of urine accompanied or immediately proceeded by urgency, derived from the number of incontinence episodes recorded by the patient in a 3-day micturition diary
Changes from Week 12 to Week 20 in OABSS
Changes from Week 12 to Week 20 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS represents a better outcome)
Changes from Week 12 to Week 20 in IPSS
Changes from Week 12 to Week 20 in IPSS (International Prostate Symptom Score) (a lower IPSS represents a better outcome)
Changes from Week 12 to Week 20 in Mean Number of Micturitions per 24 Hours
The average number of micturitions (urinations) per 24 hours is derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a 3-day micturition diary.
Changes from Week 12 to Week 20 in Mean Number of Nocturia Episodes per 24 Hours
Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinates (excluding incontinence only episodes) during sleeping time per day is derived from the 3-day patient micturition diary.
Changes from Week 12 to Week 20 in Mean Number of Urgency Episodes per 24 Hours
The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) derived from episodes recorded by the patient in a 3-day micturition diary
Changes from Week 12 to Week 20 in Mean Number of Urgency Incontinence Episodes per 24 Hours
The involuntary leakage of urine accompanied or immediately proceeded by urgency, derived from the number of incontinence episodes recorded by the patient in a 3-day micturition diary
Changes from baseline to Week 12 and 20/end of treatment (EoT) in Overactive Bladder Questionnaire-Short Form (OAB-Q-SF) score
Overactive Bladder Questionnaire-Short Form (OAB-Q-SF) is a participant-reported instrument consisting of 19 items that assess the degree to which a participant is bothered by OAB symptoms, and the degree of impact of OAB symptoms on daily life. Participants rate each item using a 6-point Likert Scale ranging from "Not at all" to "A very great deal" for the symptom bother items and "none of the time" to "All of the time" for the Health Related Quality of Life (HRQL) items.
Changes from baseline to Week 12 and 20/end of treatment (EoT) in Bladder Assessment Tool (BAT) score
Bladder Assessment Tool (BAT) is a participant-reported instrument consisting of 17 questions regarding the symptoms, bothering, impacts and treatment satisfaction in the past 7 days. Scores range from 0 to 88, a reduction in BAT score indicates an improvement.
Changes from baseline to Week 12 and 20/end of treatment (EoT) in Treatment Satisfaction-Visual Analog Scale (TS-VAS) score
Treatment Satisfaction-Visual Analog Scale (TS-VAS) is a quantitative instrument assessing participant improvement in participants with OAB. A score of 10 on the TS-VAS indicates complete satisfaction, whereas a positive change from baseline indicates improvement.

Full Information

First Posted
November 22, 2021
Last Updated
December 27, 2021
Sponsor
Taipei Veterans General Hospital, Taiwan
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1. Study Identification

Unique Protocol Identification Number
NCT05188742
Brief Title
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

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
November 10, 2021 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Taipei Veterans General Hospital, Taiwan

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Overactive Bladder Syndrome
Keywords
overactive bladder, mirabegron, transcutaneous tibial nerve stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
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
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sequence A
Arm Type
Experimental
Arm Description
mirabegron 50mg OD x 8 weeks, followed by mirabegron 50mg OD and TTNS for 4 weeks, followed by TTNS twice a week x 8 weeks
Arm Title
Sequence B
Arm Type
Experimental
Arm Description
TTNS twice a week x 8 weeks, followed by mirabegron 50mg OD and TTNS for 4 weeks, followed by mirabegron 50mg OD x 8 weeks
Intervention Type
Drug
Intervention Name(s)
mirabegron
Intervention Description
mirabegron 50mg QD
Intervention Type
Procedure
Intervention Name(s)
TTNS
Intervention Description
transcutaneous tibial nerve stimulation
Primary Outcome Measure Information:
Title
Changes from baseline to end of treatment (EoT) (Week 20) in OABSS
Description
Changes from baseline to Week 20 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS score represents a better outcome). Symptom improvement is defined as OABSS total score decreased by ≥ 3 points at EoT
Time Frame
Baseline and Week 20
Secondary Outcome Measure Information:
Title
Changes from baseline to Week 12 in OABSS
Description
Changes from baseline to Week 12 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS score represents a better outcome)
Time Frame
Baseline and Week 12
Title
Changes from baseline to Week 12 and 20/end of treatment (EoT) in IPSS
Description
Changes from baseline in IPSS (International Prostate Symptom Score) at Week 12 and 20 (a lower IPSS represents a better outcome)
Time Frame
Baseline, and Week 12 and 20
Title
Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Micturitions per 24 Hours
Description
The average number of micturitions (urinations) per 24 hours is derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a micturition diary for 3-days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
Time Frame
Baseline, and Week 12 and 20
Title
Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Nocturia Episodes per 24 Hours
Description
Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinates (excluding incontinence only episodes) during sleeping time per day is derived from a micturition diary in which a patient records for 3 days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
Time Frame
Baseline, and Week 12 and 20
Title
Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Urgency Episodes per 24 Hours
Description
The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) is derived from episodes reocrded by the patient in a micturition diary in which a patient completes for 3 days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
Time Frame
Baseline, and Week 12 and 20
Title
Change from Baseline to Week 12 and 20/end of treatment (EoT) in Mean Number of Urgency Incontinence Episodes per 24 Hours
Description
The involuntary leakage of urine accompanied or immediately proceeded by urgency, derived from the number of incontinence episodes recorded by the patient in a micturition diary in which a patient completes for 3 days prior to clinic visits at Baseline and Week 12 and 20/end of treatment (EoT).
Time Frame
Baseline, and Week 12 and 20
Title
Changes from Week 8 to Week 20 in OABSS
Description
Changes from Week 8 to Week 20 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS represents a better outcome)
Time Frame
Week 8 to Week 20
Title
Changes from Week 8 to Week 20 in IPSS
Description
Changes from Week 8 to Week 20 in IPSS (International Prostate Symptom Score) (a lower IPSS represents a better outcome)
Time Frame
Week 8 to Week 20
Title
Changes from Week 8 to Week 20 in Mean Number of Micturitions per 24 Hours
Description
The average number of micturitions (urinations) per 24 hours is derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a 3-day micturition diary.
Time Frame
Week 8 to Week 20
Title
Changes from Week 8 to Week 20 in Mean Number of Nocturia Episodes per 24 Hours
Description
Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinates (excluding incontinence only episodes) during sleeping time per day is derived from the 3-day patient micturition diary.
Time Frame
Week 8 to Week 20
Title
Changes from Week 8 to Week 20 in Mean Number of Urgency Episodes per 24 Hours
Description
The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) derived from episodes recorded by the patient in a 3-day micturition diary
Time Frame
Week 8 to Week 20
Title
Changes from Week 8 to Week 20 in Mean Number of Urgency Incontinence Episodes per 24 Hours
Description
The involuntary leakage of urine accompanied or immediately proceeded by urgency, derived from the number of incontinence episodes recorded by the patient in a 3-day micturition diary
Time Frame
Week 8 to Week 20
Title
Changes from Week 12 to Week 20 in OABSS
Description
Changes from Week 12 to Week 20 in OABSS (Overactive Bladder Symptom Score) (a lower OABSS represents a better outcome)
Time Frame
Week 12 to Week 20
Title
Changes from Week 12 to Week 20 in IPSS
Description
Changes from Week 12 to Week 20 in IPSS (International Prostate Symptom Score) (a lower IPSS represents a better outcome)
Time Frame
Week 12 to Week 20
Title
Changes from Week 12 to Week 20 in Mean Number of Micturitions per 24 Hours
Description
The average number of micturitions (urinations) per 24 hours is derived from the number of times a patient urinates (excluding incontinence only episodes) per day recorded by the patient in a 3-day micturition diary.
Time Frame
Week 12 to Week 20
Title
Changes from Week 12 to Week 20 in Mean Number of Nocturia Episodes per 24 Hours
Description
Nocturia is defined as waking at night one or more times to void. The average number of times a patient urinates (excluding incontinence only episodes) during sleeping time per day is derived from the 3-day patient micturition diary.
Time Frame
Week 12 to Week 20
Title
Changes from Week 12 to Week 20 in Mean Number of Urgency Episodes per 24 Hours
Description
The average number of urgency episodes (the sudden, compelling desire to pass urine that is difficult to defer) derived from episodes recorded by the patient in a 3-day micturition diary
Time Frame
Week 12 to Week 20
Title
Changes from Week 12 to Week 20 in Mean Number of Urgency Incontinence Episodes per 24 Hours
Description
The involuntary leakage of urine accompanied or immediately proceeded by urgency, derived from the number of incontinence episodes recorded by the patient in a 3-day micturition diary
Time Frame
Week 12 to Week 20
Title
Changes from baseline to Week 12 and 20/end of treatment (EoT) in Overactive Bladder Questionnaire-Short Form (OAB-Q-SF) score
Description
Overactive Bladder Questionnaire-Short Form (OAB-Q-SF) is a participant-reported instrument consisting of 19 items that assess the degree to which a participant is bothered by OAB symptoms, and the degree of impact of OAB symptoms on daily life. Participants rate each item using a 6-point Likert Scale ranging from "Not at all" to "A very great deal" for the symptom bother items and "none of the time" to "All of the time" for the Health Related Quality of Life (HRQL) items.
Time Frame
Baseline, and Week 12 and 20
Title
Changes from baseline to Week 12 and 20/end of treatment (EoT) in Bladder Assessment Tool (BAT) score
Description
Bladder Assessment Tool (BAT) is a participant-reported instrument consisting of 17 questions regarding the symptoms, bothering, impacts and treatment satisfaction in the past 7 days. Scores range from 0 to 88, a reduction in BAT score indicates an improvement.
Time Frame
Baseline, and Week 12 and 20
Title
Changes from baseline to Week 12 and 20/end of treatment (EoT) in Treatment Satisfaction-Visual Analog Scale (TS-VAS) score
Description
Treatment Satisfaction-Visual Analog Scale (TS-VAS) is a quantitative instrument assessing participant improvement in participants with OAB. A score of 10 on the TS-VAS indicates complete satisfaction, whereas a positive change from baseline indicates improvement.
Time Frame
Baseline, and Week 12 and 20

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chih-Chieh Lin, MD/Phd
Phone
+886-2-2875-7808
Email
jayslylin@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chih-Chieh Lin, MD/Phd
Organizational Affiliation
Taipei Veterans General Hospital, Taiwan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Taipei Veterans General Hospital
City
Taipei City
ZIP/Postal Code
11217
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chih-Chieh Lin, MD/Phd
Phone
+886-2-2875-7808
Email
jayslylin@gmail.com

12. IPD Sharing Statement

Learn more about this trial

Sequencing and Combination of Mirabegron and TTNS in Overactive Bladder Syndrome: a Multicenter, Randomized, Open-label, Crossover Trial

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