Clinical trial NCT02900495: Transcutaneous Electric Nerve Stimulation (TENS) for the Treatment of Nocturnal Enuresis in Children
Official title: Transcutaneous Electric Nerve Stimulation (TENS) for the Treatment of Nocturnal Enuresis in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nocturnal Enuresis
Bedwetting
Keywords: Nocturnal Enuresis
Bedwetting
TENS
Lead sponsor: Northwell Health
Sponsor class: OTHER
Collaborators: name: Feinstein Institute for Medical Research
name: Albany Medical College
First posted: 2016-09-14
Enrollment: 147
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Children referred to the pediatric urology clinic for primary nocturnal enuresis will be screened for enrollment. Patients who fail behavioral therapy and who meet inclusion criteria will be offered therapy with a TENS unit.

Patients will be randomized into four groups. Group 1 will be the direct bladder stimulation arm with electrodes placed onto the abdomen in the suprapubic region directly over the bladder. Group 2 will be the distal neural loop arm with electrodes placed over the posterior tibial nerve. Group 3 will be the proximal neural loop arm with electrodes placed about 2-3 cm lateral to the midline in the sacral region at the level of S3. Group 4 will be the control arm with electrodes placed on the scapula. We will aim to recruit 32 patients per group for a total of 128 patients. The patients will be provided with a TENS unit (TENS 3000 Analog) and electrode pads and caretakers instructed on how to use the apparatus.

The TENS sessions will be performed nightly before bed for 15 minutes. TENS units will be set at a frequency of 10 Hz, and intensity determined by the sensitivity threshold of the patient. Diaries including nighttime incontinence episodes and a "wet sheet" scale (dry, damp, wet, soaked) will be recorded, along with any adverse reactions to the TENS unit. Patients will be followed up after one month of TENS with evaluation including the Pediatric Urinary Incontinence Questionnaire, a validated tool for measuring quality of life in children with bladder dysfunction; this questionnaire will be filled out prior to starting TENS treatment in order to compare the effect of treatment on QOL. . They will then follow up on these parameters again after another month (one month off of TENS therapy) to assess the durability of treatment effect. The data will be collected at different time points (baseline, 1 month, 2 months) for each group by itself and the groups compared against each other using statistical analysis.

Detailed description: Institutional review board was obtained. Children ages 5-18 years old referred to the pediatric urology clinic for primary nocturnal enuresis will be screened for enrollment. Behavioral therapy (limiting evening drinking, double voiding prior to bedtime, bowel habits, social anxiety factors) will be utilized first. Patients who fail will next be offered therapy with a bedwetting alarm device or a TENS unit as an alternative, and those who chose TENS therapy will be included in the study. Patients who have previously tried pharmacologic treatment for nocturnal enuresis, neuromodulation or other alternative therapy for urologic disorders, daytime incontinence symptoms, known "high volume" voiders (determined from history), bedwetting episodes on the average of less than two times per week, medications predisposing to incontinence (eg, Lithium for bipolar disorder), other known voiding or neurologic disorders (eg, overactive bladder, myelomeningocele), secondary etiologies for nocturnal enuresis (eg, cystitis, obstructive sleep apnea, urinary fistulae), and any contraindications to usage of a TENS unit such as having a pacemaker will be excluded. Patients who have previously tried the bedwetting alarm will not be excluded from the study. 128 patients will be chosen for enrollment into the study.

The patients will be randomized into four groups of 32 patients each. Group 1 will be the direct bladder stimulation arm with electrodes placed onto the abdomen in the suprapubic region directly over the bladder. Group 2 will be the distal neural loop arm with electrodes placed onto the bottom of the feet. Group 3 will be the proximal neural loop arm with electrodes placed about 2-3 cm lateral to the midline in the sacral region at the level of S3. Group 4 will be the sham arm with electrodes placed on the scapula. We will aim to recruit 32 patients per group for a total of 128 patients. Detailed explanation of the purpose of the study, along with the risks and benefits of TENS will be given to the patient and caretakers by a provider prior to obtaining informed consent for enrollment into the study. The patients will be provided with a TENS unit and electrode pads and caretakers instructed on how to use the apparatus.

Parents of enrolled patients will fill out nightly voiding diaries, recording nighttime incontinence episodes and subjective "wet sheets" scale per night (dry, damp, wet, soaked) for 30 days prior to randomization into the treatment arms. The TENS sessions will be performed nightly at bedtime for 15 minutes for 30 days. TENS units will be set at a frequency of 10 Hz, and intensity determined in the office by the sensitivity threshold of the patient. Voiding diaries will be kept each night while on TENS therapy, additionally recording which TENS setting was used, duration of therapy each night, and any adverse reactions to the TENS unit or increased symptoms (these patients will be terminated from the study and included as a treatment failure). Diaries will then be kept for 30 days after TENS therapy was completed to assess durability of treatment effects. At voiding diary day 30 (before first TENS treatment), day 60 (after completion of TENS therapy), and day 90 (one month off of TENS), patients and families will fill out the Pediatric Urinary Incontinence Questionnaire (PIN-Q), a validated tool for measuring quality of life in children with bladder dysfunction. Patients will follow up at days 0, 30, 60, 90, and as needed (worsening symptoms, adverse reactions, concerns, and questions regarding usage of TENS). Parents will be called on a weekly basis throughout the study to ensure compliance and address any questions or concerns. The results of mean nightly incontinence episodes, mean "wet sheets" scale score (0-3), and PIN-Q will be measured between time points (baseline, 1 month, 2 months for each group by itself and the groups compared against each other using statistical analysis.

Eligibility criteria: Inclusion Criteria:

* primary nocturnal enuresis
* wet nights occur more than once per week on average
* Failed Behavioral therapy treatment (limiting evening drinking, double voiding prior to bedtime, bowel habits, social anxiety factors)
* ability to provide informed consent and complete study requirements

Exclusion Criteria:

* the use of medications for nocturnal enuresis (DDAVP, imipramine, anticholinergics) less than 30 days from time of appointment
* daytime incontinence
* Known "high volume" voiders
* medications predisposing to incontinence (eg, Lithium for bipolar disorder)
* other known voiding or neurologic disorders (eg, overactive bladder, spina bifida, interstitial cystitis)
* secondary etiologies for nocturnal enuresis (cystitis, obstructive sleep apnea, urinary fistula)
* any contraindication to TENS unit usage (pacemaker or other implantable devices, lymphedema, pregnancy, malignancy)
* Any history of heart disease or complications

Primary outcomes:
measure: Change in Wet nights
timeFrame: 60 days
Secondary outcomes:
measure: Severity
timeFrame: 60 days
measure: Patient compliance
timeFrame: 60 days
measure: Quality of Life Scores
timeFrame: 60 days
measure: Adverse reactions
timeFrame: 60 days
measure: Durability
timeFrame: 90 days
Other outcomes:
Locations:
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Brooklyn
country: United States
facility: Pediatric Urology Associates
state: New York
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center of NY
state: New York
city: New Hyde Park
country: United States
facility: Pediatric Urology Associates
state: New York
city: Tarrytown
country: United States
facility: Pediatric Urology Associates
state: New York
Study officials:
affiliation: Cohen Children's Medical Center of NY
name: Lane S Palmer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kajbafzadeh AM, Sharifi-Rad L, Mozafarpour S, Ladi-Seyedian SS. Efficacy of transcutaneous interferential electrical stimulation in treatment of children with primary nocturnal enuresis: a randomized clinical trial. Pediatr Nephrol. 2015 Jul;30(7):1139-45. doi: 10.1007/s00467-014-3039-5. Epub 2015 Jan 25.
citation: Lordelo P, Benevides I, Kerner EG, Teles A, Lordelo M, Barroso U Jr. Treatment of non-monosymptomatic nocturnal enuresis by transcutaneous parasacral electrical nerve stimulation. J Pediatr Urol. 2010 Oct;6(5):486-9. doi: 10.1016/j.jpurol.2009.11.005.
citation: Barroso U Jr, Lordelo P, Lopes AA, Andrade J, Macedo A Jr, Ortiz V. Nonpharmacological treatment of lower urinary tract dysfunction using biofeedback and transcutaneous electrical stimulation: a pilot study. BJU Int. 2006 Jul;98(1):166-71. doi: 10.1111/j.1464-410X.2006.06264.x.