Clinical trial NCT06883851: Effectiveness of Pelvic Floor Muscle Rehabilitation Combined With Desmopressin in Children With Primary Monosymptomatic Nocturnal Enuresis
Official title: Evaluating the Efficacy of Structured Pelvic Floor Muscle Rehabilitation Combined With Desmopressin in the Management of Primary Monosymptomatic Nocturnal Enuresis in Children
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Primary Nocturnal Enuresis
Nocturnal Enuresis in Children
Keywords: biofeedback
core stabilization
exercise
urinary incontinence
management
treatment
enuresis
pelvic floor rehabilitation
desmopressin
Lead sponsor: Bahçeşehir University
Sponsor class: OTHER
Collaborators: name: Private Selcuk Sılay Pediatric Urology Clinic
name: Medipol Acıbadem Regional Hospital
First posted: 2025-03-19
Enrollment: 40
Sex: ALL
Minimum age (years): 7
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Children aged 7 to 13 years, diagnosed with PMNE and meeting the inclusion criteria, will be included in the study. The sample size for the study will be determined after data collection from a pilot study involving ten participants.
Primary purpose: TREATMENT

Brief summary: The aim of this randomized controlled trial is to evaluate the effects of Structured Pelvic Floor Muscle Rehabilitation (SPFMR) in children with Primary Monosymptomatic Nocturnal Enuresis (PMNE) who are undergoing desmopressin asetat (DDAVP) treatment prescribed by a pediatric urologist. The study aims to investigate whether SPFMR can reduce the frequency and severity of enuresis episodes and whether it can also reduce relapse rates in the short- and long-term follow-up. The main questions the study seeks to answer are:

* Does SPFMR reduce the frequency and severity of enuresis episodes in children with PMNE?
* Does SPFMR treatment reduce relapse rates in children with PMNE in the long term? Researchers will compare the group receiving SPFMR in addition to DDAVP treatment with a control group receiving only DDAVP treatment. This comparison will help evaluate the effect of SPFMR on the severity of enuresis episodes and relapse rates.

Participants will:

* Receive DDAVP treatment (SPFMR group and Control group)
* Participate in SPFMR sessions ( SPFMR group)
* Keep a diary of enuresis frequency and severity
* Assess relapse during short- and long-term follow-up

The hypotheses of the study are:

H0: Adding SPFMR to desmopressin treatment for children with PMNE has no short-term effect on the severity of enuresis episodes.

H1: Adding SPFMR to desmopressin treatment for children with PMNE has a short-term effect on the severity of enuresis episodes.

H0: Adding SPFMR to desmopressin treatment for children with PMNE has no long-term effect on the severity of enuresis episodes.

H2: Adding SPFMR to desmopressin treatment for children with PMNE has a long-term effect on the severity of enuresis episodes.

Detailed description: Nocturnal enuresis (NE) is defined as nighttime urinary incontinence (bedwetting) during sleep in a healthy child older than five years, occurring at least twice a week for at least three consecutive months, sufficient to wet most or all of the sleeping area. NE is categorized into two types based on the presence or absence of daytime lower urinary tract symptoms (LUTS): monosymptomatic nocturnal enuresis (MNE) and non-monosymptomatic nocturnal enuresis (NMNE). MNE refers to involuntary nighttime urinary incontinence during sleep in children older than five years without any congenital or acquired urological or central nervous system (CNS) disorders and without daytime LUTS.

Approximately 80% of children diagnosed with NE are classified as having MNE. NE is further subdivided into primary and secondary subgroups based on the onset period. Primary NE refers to children who have had less than six months of dryness since toilet training, whereas secondary NE is diagnosed in children who have experienced six months or more of dryness since toilet training . In summary, primary MNE is used to diagnose children who have had less than six months of nighttime dryness since toilet training and lack daytime LUTS.

NE, previously viewed as a psychiatric disorder, is now understood to involve a variety of mechanisms and multifactorial causes. Studies suggest that children with NE exhibit a range of symptoms across different systems. The current understanding of NE's etiology includes three main factors:reduced noctural bladder capacity, nocturnal polyuria and decreased arousability during sleep.

Treatment options for MNE include urotherapy (healthy bladder and bowel training), enuresis alarms (bedwetting alarms), and pharmacological agents such as desmopressin acetate (DDAVP), anticholinergics, and tricyclic antidepressants. These methods can be used alone or in combination for the treatment of MNE. Among first-line treatments, enuresis alarms (evidence level 1A) and DDAVP (evidence level 1A) are widely accepted approaches in pediatric urology. It is estimated that approximately one-third of enuretic children may require additional treatment following first-line interventions.

DDAVP is a pharmacological agent developed as an analog of vasopressin or antidiuretic hormone. Its antienuretic effect reduces the volume of urine produced overnight, allowing the bladder to store the produced urine. Literature reports that about one-third of children undergoing DDAVP therapy achieve reliable dryness while on the medication, another third experience moderate benefits, and the remaining third see no benefit Although high relapse rates of NE have been reported following the cessation of DDAVP treatment, a recent meta-analysis showed that structured dose-dependent discontinuation of DDAVP provides better relapse-free rates.

Although DDAVP and alarm therapy, both with evidence level 1A, are established first-line treatments for MNE, research continues into additional therapies and complementary approaches that may enhance treatment success. These include chiropractic therapy, homeopathy, pelvic floor exercises, electrotherapy, breathing exercises, hypnosis, Ayurveda, reflexology, traditional Chinese and Iranian medicine, massage, yoga, and herbal treatments.

Considering the potential pharmacological side effects and the lack of adherence among families, DDAVP alone may be insufficient for treating PMNE. Additionally, given the deviations in pelvic floor muscle (PFM) activation values reported in enuretic children, it is necessary to investigate a combined approach incorporating PFM rehabilitation into medical treatment for children diagnosed with PMNE. The study's hypothesize is Structured Pelvic Floor Muscle Rehabilitation (SPFMR), applied to children with PMNE who are already receiving DDAVP therapy (as prescribed by a pediatric urology physician), will reduce the frequency and severity of enuresis episodes and decrease relapse rates in both short- and long-term follow-ups.

The study protocol will adhere to applicable regulations, the current Declaration of Helsinki, and the principles of Good Clinical Practice. Since participants are under the age of 18, written and verbal consent will be obtained from their parents. The study will commence after receiving ethics committee approval and completing the clinical trial registration.

Physiotherapy Modalities to Be Used in Structured Pelvic Floor Muscle Rehabilitation (SPFMR):

- Diaphragmatic Breathing Training: The diaphragm is not only a respiratory muscle but also a part of the core system. It works synergistically with PFM to ensure the proper function of the pelvic floor. \]. The diaphragm plays a vital role in generating proper intra-abdominal pressure and transmitting it from the cranial to the caudal regions. Additionally, the pushing pressure generated by the diaphragm is crucial for voiding (urination, defecation, and childbirth) and the functional activity of PFM. In PFMRG, diaphragmatic breathing exercises will involve inhaling through the nose for 4 seconds and exhaling through the mouth for 8 seconds in a series of 30 repetitions lasting approximately 6 minutes. Breaks will be given in case of dizziness or discomfort, after which the exercises will resume.

- Biofeedback-Assisted PFM Training Biofeedback therapy is a non-invasive, easily accessible technique for treating pediatric pelvic floor dysfunction. As a physical therapy modality, biofeedback aims to train appropriate PFM activity essential for normal, healthy bowel and bladder function. Electromyographic biofeedback is the most commonly used type for treating these dysfunctions. Biofeedback therapy is an instrument-based learning process that uses operant conditioning. It provides visual, auditory, and verbal feedback to promote self-control over physiological processes that are otherwise outside awareness or under limited voluntary control, such as autonomic and neuromuscular activity.

Before starting each session, the microvolt value produced by submaximal muscle contraction will be measured three times and recorded using the Libert Phenix device. The CE certificate and registration of the device with the Ministry of Health are provided. Subsequently, PFM will be trained with 15-second phasic contractions at 30%, 60%, and 90% of submaximal strength, followed by 10 seconds of relaxation to achieve basal relaxation. Each phasic contraction training period will be completed in 25 seconds. The phasic training period will include 24 repetitions completed in 600 seconds (10 minutes).

Following phasic contraction training, tonic contraction exercises will be performed at 30% muscle contraction based on recorded submaximal activation. Each tonic contraction will last for 10 seconds, followed by a 10-second relaxation period to achieve basal relaxation, with one tonic contraction cycle completed in 20 seconds. The tonic contraction training period will consist of 30 repetitions, completed in 600 seconds (10 minutes). The endurance training, starting at 30%, will gradually progress to 40%, 50%, 60%, and 80%.

SPFMRG participants will be taught to perform proper PFM contractions without engaging their adductor or gluteal muscles. Training will begin in the supine position and progress to seated and then standing positions to introduce gravitational effects over the weeks.

- Core Stabilization and Combined Squat Exercises: In addition to ensuring continence and supporting various pelvic organs, PFMs are a component of the local stabilization system, playing a critical role in the lumbopelvic region in association with the transversus abdominis and multifidus muscles. These muscles work synergistically with other muscles surrounding the abdominal cavity, such as the anterolateral abdominal muscles and thoracic diaphragm, to regulate intra-abdominal pressure and ensure abdominal stability. Core stabilization exercises will follow the Dynamic Neuromuscular Stabilization (DNS) method, based on developmental kinesiology. DNS focuses on the integrated spinal stabilization system, targeting deep cervical flexors, the diaphragm, transversus abdominis, multifidus, and PFMs, by mimicking stabilization patterns observed in healthy infants.

DNS exercises aim to activate the spinal stabilization system effectively through repetition and help individuals regain control during various tasks. While DNS methods have been studied for urinary incontinence in adults, studies are needed on pediatric incontinence. DNS methods have been applied in pediatric populations with cerebral palsy.

DNS Exercises:

* Crawling Bug: Supine position with a 55 cm Pilates ball positioned between the feet and hands, rotating the ball 5 times x 3 sets.
* Rocking Bear: Quadruped position, lifting and lowering the knees 5 cm above the mat, 10 repetitions x 3 sets.
* Reaching Cat: Cross-extension exercise with a resistance band looped around the foot, one end held by the participant in a quadruped position, 10 repetitions x 3 sets.
* Showering Elephant: Holding a 55 cm Pilates ball between the hands, synchronizing squats with lifting the ball to shoulder height, 10 repetitions x 3 sets.
* External Rotator and Adductor Strengthening:

Strengthening the external rotator muscles, including the obturator internus (OI), has been shown to play a synergistic role in enhancing PFM function and strength. It has also been reported as an easily applicable and comprehensible auxiliary exercise for women with reduced PFM contraction ability. While studies on the role of OI in PFM rehabilitation are abundant in adult women, pediatric studies are limited and primarily case studies . Participants will perform abduction and external rotation of the lower extremities with a resistance band placed between the knees, 10 repetitions x 3 set.

While studies on the role of OI in PFM rehabilitation are abundant in adult women, pediatric studies are limited and primarily case studies. Participants will perform abduction and external rotation of the lower extremities with a resistance band placed between the knees, 10 repetitions x 3 set.

- Balance Training: Participants will perform balance exercises on a Bosu ball in both double-leg and single-leg stances, with eyes open and closed, for 30 seconds x 3 sets.

- Home Exercises: Participants will be asked to perform the following home exercises three times per week.

* Diaphragmatic breathing exercises: Inhaling for 4 seconds, exhaling for 8 seconds, 30 repetitions (approximately 6 minutes).
* PFM contractions: 10 seconds of contraction, followed by 10 seconds of relaxation, for 6 cycles.
* 10 squat exercises.
* Crawling Bug and Rocking Bear exercises: 30 seconds x 3 sets. Participants will be provided with a home exercise tracking chart, monitored weekly by the research physiotherapist.

After the treatment, participants' dry nights and symptoms will be converted into percentages following the ICCS treatment outcome recommendations. According to this recommendation, a reduction of less than 50% in symptoms will be considered no response to treatment; a reduction of 50% to 99% in symptoms will be considered a partial response, and the complete resolution of symptoms (100% reduction) will be considered full success.

Eligibility criteria: Inclusion Criteria:

* Being between 7 and 13 years old
* Diagnosed with primary MNE by a pediatric urology department within the last 6 months
* No urinary tract infection verified by laboratory tests
* Ability to communicate in Turkish and absence of mental deficit
* No diagnosed psychiatric problems
* Willingness to participate in the study (child and family)

Exclusion Criteria:

* Presence of orthopedic conditions preventing evaluation
* Anatomical anomalies in the urinary system
* History of urinary system surgery
* Neurological disorders
* Presence of mental retardation
* History of orthopedic surgery that could alter pelvic or lower extremity integrity
* Receiving PFM rehabilitation in the last 6 months
* Using nighttime alarm therapy in the last 6 months
* Receiving any treatment for enuresis in the last 6 months

Primary outcomes:
measure: The Nighttime Bedwetting Diary
timeFrame: baseline; 10th week after baseline; 12th week after baseline and 16th week after baseline
Secondary outcomes:
measure: Uroflowmetry Test
timeFrame: baseline; 10th week after baseline; 12th week after baseline and 16th week after baseline
measure: Post-Void Residual (PVR) Assessment
timeFrame: baseline; 10th week after baseline; 12th week after baseline and 16th week after baseline
measure: Bladder Diary
timeFrame: baseline; 10th week after baseline; 12th week after baseline and 16th week after baseline
measure: Pelvic Floor Muscle Activation Measurement
timeFrame: baseline; 10th week after baseline; 12th week after baseline and 16th week after baseline
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Private Selcuk Silay Pediatric Urology Clinic
state: Beşiktaş
city: Istanbul
country: Turkey
facility: Medipol Acıbadem Region Hospital
state: Kadıkoy
Study officials:
affiliation: Bahçeşehir University
name: Pelin Pisirici, Assist. Prof.
role: STUDY_DIRECTOR
affiliation: Medipol University
name: Mesrur Selcuk Silay, Prof. Dr.
role: STUDY_CHAIR
affiliation: Bahçeşehir University
name: Aygul Koseoglu Kurt, Ph.D. (c)
role: PRINCIPAL_INVESTIGATOR
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