Clinical trial NCT05668715: Transcutaneous Tibial Nerve Stimulation in Antimuscarinic Naive and Refractory Women With Idiopathic Overactive Bladder
Official title: Comparison of the Efficacy of Transcutaneous Tibial Nerve Stimulation in Antimuscarinic Naive and Refractory Women With Idiopathic Overactive Bladder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Urinary Bladder, Overactive
Lead sponsor: Pamukkale University
Sponsor class: OTHER
First posted: 2022-12-30
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study is the first prospective trial that compares the efficacy of TTNS in antimuscarinic naive and refractory women with idiopathic OAB. In this study, it was aimed to compare the effectiveness of TTNS on quality of life (QoL) and clinical parameters related to OAB in antimuscarinic naive and refractory women. The results of this study would make it easier to understand the place of TTNS among the treatment options in women with idiopathic OAB.

Detailed description: This study was planned as a prospective clinical trial. The trial was carried out in the Urogynecological Rehabilitation Unit of Physical Medicine and Rehabilitation Department, in between January 2023 and June 2023. The local ethics committee approved the study. All women were informed about the purpose and contents of the study and all women signed written consent to participate in the study.

As previously published by Sonmez et al , BT+IVES succeeded to reduce mean incontinence episodes from 4.40±3.43 to 0.70±0.57 after treatment in the active comparator group while mean incontinence episodes was reduced from 4.15±1.67 to 2.68±1.66 after treatment in the control group (BT). Considering a 50% or greater improvement in incontinence episodes in the referred study, the optimum sample size should be 18 cases in each arm with a level of significance of 95% (α=5%), a power of 95% (ß=0.05) . Taking into account possible withdrawals which was assumed to be about 10% of the number of patients, a total of 40 women (20 women for each group) were calculated for this study. Sample size calculation was performed by the physician using G\*Power 3.1 Statistical Power Analysis for Microsoft Windows and Mac. Statistics.

To investigators recruited women with complaints of OAB who were referred to the Urogynecological Rehabilitation Unit and other related outpatient clinics. Women over the age of 18 with the clinical diagnosis of idiopathic OAB, and who could able to give written informed consent and understand the procedures were included in this study. The criteria for exclusion were as follows. Women who had stress urinary incontinence; a history of PTNS and/or TTNS for OAB within 6 months; urogynecological surgery within 3 months; current vulvovaginitis or urinary tract infections or malignancy; pregnancy; cardiac pacemaker or implanted defibrillator; anatomic or posttraumatic malformations/skin disorders of tibial nerve region on inner ankle that can not allow to apply the electrodes; the strength of PFM less than 3/5 (graded as modified Oxford scale, min:0-max:5); the pelvic organ prolapse quantification (POP-Q) (stage 2 or more); neurogenic bladder; the peripheral or central neurologic pathology; ultrasonographic evidence of post-void residual urine volume more than 100 ml were excluded.

Women with idiopathic OAB were recruited for eligibility and of them who fulfilled the inclusion/exclusion criteria were included for this study. Antimuscarinic naive women were included in Group 1 (n:20), and women resistant to anti-muscarinic agents were included in Group 2 (n:20). Both groups received BT plus TTNS.

Group 1: Antimuscarinic Naive (AM-N) None of the women had previously taken anti-muscarinic agents and oral ß3 adrenoreceptor agonist (mirabegron) in this group.

Group 1: Antimuscarinic Refractory (AM-R) Women with idiopathic OAB refractory to anti-muscarinic agents and oral ß3 adrenoreceptor agonist (mirabegron) when 2 or more were administered for at least 6 weeks each and failure was due to lack of efficacy with or without side effects were included in this group.

Bladder Training (BT) All women were informed about BT that consisted of four stages and lasted for 30 minutes. Then, it was given as a written brochure to be implemented as a home program. At the first stage, the women were familiarized with the location of the PFM and the pelvic anatomy and pathophysiology. After that information session, squeezing the PFM was shown in practice at least once to use in the urgency suppression strategies via digital palpation technique. The second stage including urgency suppression strategies was aimed to delay urination, inhibit detrusor contraction, and prevent urgency by squeezing the PFM several times on a row, breathing deeply, giving their attention to another job for a while, and self-motivating. In the third stage, a timed voiding program was started. It was carried out in 2 steps: a timed voiding and increasing the time between urination considering the voiding diary. At the last stage, the women were encouraged to continue BT.

Transcutaneous tibial nerve stimulation (TTNS) Two self-adhesive surface electrodes were positioned according to the protocol used by Booth et al and Shreiner et al, with the negative electrode 2 cm behind the medial malleolus and positive electrode 10 cm proximal to it. Correct positioning was determined by noting a hallux reaction (plantar flexion of great toe or fanning of all toes). The stimulation protocol was delivered at fixed of 20 Hz and pulse width of 200 ms in continous mode in accordance with PTNS stimulation protocol. The intensity level of the stimulation current (range 0-50 mA) was determined once correct positioning was established, according to the comfort level of the subject. TTNS sessions were performed two times in a week, for 6 weeks. Every session lasted 30 minutes. The intervention comprised a 12 session treatment program of TTNS.

TTNS sessions were performed by an experienced urogynecological rehabilitation nurse in all groups. During the treatment, all women were advised to continue the medical treatment which was not related to incontinence. Participants were asked to fill in a one-day bladder diary biweekly to continue the timed voiding program, which is part of BT in two groups. Compliance with the BT was achieved with the daily checklist during 6 weeks and the bladder diaries of women were checked biweekly to rearrange the timed voiding program. Women who did not fill more than 20% of the daily checklist and who missed any therapy sessions for two groups were excluded from the study.

Evaluation Parameters The primary outcome measure was accepted as the improvement in incontinence episodes (positive response rate), according to literature . To determine positive response rate, reduction in incontinence episodes was collected from the 3-day bladder diary. Women with ≥a 50% reduction in incontinence episodes were considered positive responders. Furthermore, the severity of incontinence, PFM strength, symptom severity, frequency of voiding, nocturia, number of pads as well as QoL were secondary outcome measures. The 24-hour pad test was carried out to evaluate the severity of incontinence. Overactive Bladder Questionnaire (OAB-V8) was used to evaluate the symptom severity in patients with OAB in this study. The OAB-V8 consists of 8 questions in which the patients can be classified with respect to the symptom severity: none (0), very little (1), a little (2), quite a few (3), very (4), and too many (5). The total score ranges from 0-40. The frequencies of voiding, nocturia, and the number of pads used were collected from the 3-day bladder diary. The Quality of Life-Incontinence Impact Questionnaire (IIQ7) was used to assess specific QoL related to incontinence. In addition, cure-improvement rate and treatment satisfaction were evaluated. In a 24-hour pad test, amount of urine that was under 1.3 gr was considered as a cure. The improvement rate was assessed in terms of 50% and more reduction in wet weight compared to baseline measurements in the 24-hour pad test . Women evaluated the change in their urinary incontinence on a 5-point Likert scale (5, very satisfied; 1, very unsatisfied). All the evaluation tests were performed by another physician who was blinded to the groups in the initial visit and at the end of the treatment (8th week), except for the positive response rate, cure/improvement rate, and the treatment satisfaction parameters which were evaluated only at the 8th week.

Statistics SPSS17.0 software (SPSS, Chicago, IL) was used for the statistical analysis. In each group, measurable parameters were tested with the Kolmogorov-Smirnov test for the evaluation of normal distribution. Because the distributions were not normal, non-parametric tests were used in the statistical evaluation. Mann-Whitney U-test and χ2 test were used for inter-group comparisons. Wilcoxon tests were used for intra-group comparison of parameters at different point of times. P\<0.05 was accepted as statistically significant.

Eligibility criteria: Inclusion Criteria:

1. Women 18 years and older with clinically idiopathic OAB
2. Having the ability to give written informed consent
3. Ability to understand procedures

Exclusion Criteria:

1. Presence of active vaginal or urinary tract infection or malignancy
2. Pregnancy or intention to become pregnant during the study
3. History of neurogenic bladder, peripheral or central neurological pathology
4. Presence of Grade 2 and higher pelvic organ prolapse (POP) according to the International Continence Society (ICS)
5. Having undergone urogynecological surgery in the last 3 months
6. Women with stress urinary incontinence
7. History of PTNS and/or TTNS for OAB in the past 6 months
8. Presence of a pacemaker or implanted defibrillator
9. Presence of anatomical or post-traumatic malformations / skin disorders of the tibial nerve region of the inner ankle that do not allow the application of electrodes
10. PTK strength less than 3/5 (rated as modified Oxford scale, min: 0-max: 5)
11. Ultrasonographic evidence of a postvoid residual urine volume greater than 100 ml

Primary outcomes:
measure: İmprovement in incontinence episodes
timeFrame: 6 months
Secondary outcomes:
measure: Severity of incontinence
timeFrame: 6 months
measure: The frequencies of voiding
timeFrame: 6 months
measure: Cure-improvement rate
timeFrame: 6 months
measure: Change in their urinary incontinence
timeFrame: 6 months
measure: Nocturia
timeFrame: 6 months
measure: The number of pads
timeFrame: 6 months
measure: The Quality of Life
timeFrame: 6 months
measure: Treatment satisfaction
timeFrame: 6 months
Other outcomes:
Locations:
city: Denizli
country: Turkey
facility: Pamukkale University
Study officials:
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