A Cohort Study on Treating Primary Nocturnal Enuresis by Regulating Central-Peripheral Circadian Rhythm

NCT ID: NCT07003126

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-01
• Study Completion Date: 2028-06-01

Brief Summary

Primary nocturnal enuresis (PNE), a prevalent pediatric disorder, suffers from therapeutic limitations characterized by low efficacy and high relapse rates. Targeting its core pathophysiology could significantly improve treatment outcomes. Growing evidence implicates circadian dysregulation in PNE pathogenesis. Our preliminary fMRI cohort identified abnormal functional connectivity between the suprachiasmatic nucleus (SCN, the central circadian pacemaker) and superior temporal gyrus in PNE patients, with clinical data confirming circadian realignment correlates with symptom remission. Small-scale pilot studies and clinical observations indicate that modulating central and peripheral circadian rhythms significantly alleviates PNE symptoms. This study will establish a circadian-focused PNE cohort to quantify therapeutic efficacy and elucidate underlying mechanisms, ultimately driving the development of mechanism-based therapies for PNE.

Detailed Description

The intervention training will last for 6 months. Researchers will compare the therapeutic efficacy of the "Circadian Rhythm Intervention Combined with Bladder Training Group (treatment group)" and the "Bladder Training (basic treatment for enuresis) Only Group (control group)" for PNE.

Participants will be assigned to either the "Circadian Rhythm Intervention Combined with Bladder Training Group (treatment group)" or "Bladder Training (basic treatment for enuresis) Only Group (control group)" through stratified block randomization matching participants by sex (male/female), age (in years), and enuresis frequency. Within each stratified subgroup, block randomization with a 1:1 allocation ratio will be implemented using computer-generated random sequences, ensuring balanced demographic distribution between the two intervention arms while maintaining concealment of allocation sequence.

In the "Circadian Rhythm Intervention Combined with Bladder Training Group (treatment group)", participants will receive a 6-month behavioral therapy including both bladder training and circadian rhythm intervention. Bladder training combined with circadian rhythm interventions involves sleep hygiene optimization, individualized chronotype alignment, morning bright light therapy and bladder training component. The bladder training component (basic treatment for enuresis) includes fluid intake modification, micturition desire-relaxation training, and sphincter control training. Clinical symptom severity and key pathophysiological parameters will be evaluated at baseline and at 6 months post-intervention.

In the "Bladder Training Only Group (control group)", participants will receive a 6-month behavioral therapy including only bladder training. The bladder training component (basic treatment for enuresis) includes fluid intake modification, micturition desire-relaxation training, and sphincter control training. Clinical symptom severity and key pathophysiological parameters will be evaluated at baseline and 6 months post-intervention.

The investigators will compare changes in enuresis improvement rate, resting-state functional magnetic resonance imaging data, sleep physiological parameters, salivary melatonin levels, diurnal and nocturnal urine volume, standardized bladder capacity, and grade scoring of the micturition desire-awakening function before and after the intervention.

Conditions

Primary Nocturnal Enuresis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Circadian Rhythm Intervention Combined with Bladder Training

The study population consists of children diagnosed with primary nocturnal enuresis according to the diagnostic criteria established by the International Children's Continence Society (ICCS). Participants will receive bladder training including fluid intake modification, micturition desire-relaxation training and sphincter control training combined with circadian rhythm interventions, including sleep hygiene education, chronotype-guided bedtime scheduling, and morning bright light therapy. Clinical symptom severity and key pathophysiological measures will be assessed at baseline and 6 months after intervention initiation.

Group Type: EXPERIMENTAL

Circadian Rhythm Intervention Combined with Bladder Training

Intervention Type: BEHAVIORAL

Participants diagnosed with primary nocturnal enuresis will be screened at Shanghai Children's Medical Center, and eligible patients will be enrolled. Participants will be randomly assigned to the Bladder Training Combined with Circadian Rhythm Intervention Group, which will receive a 6-month integrated protocol encompassing bladder training and circadian rhythm intervention. The bladder training component includes fluid intake restriction, micturition desire-relaxation training, and sphincter control training. Circadian rhythm interventions involve sleep hygiene education, chronotype-guided bedtime scheduling, and morning bright light therapy.

Bladder Training (basic treatment for enuresis)

The study population consists of children diagnosed with primary nocturnal enuresis according to the ICCS criteria. Participants will undergo bladder training interventions, specifically including fluid intake modification, micturition desire-relaxation training and sphincter control training. The clinical symptom progression will be monitored, and key outcome measures will be prospectively collected at two timepoints: baseline (pre-intervention) and 6 months after intervention initiation.

Group Type: ACTIVE_COMPARATOR

Bladder Training (basic treatment for enuresis)

Intervention Type: BEHAVIORAL

Participants diagnosed with primary nocturnal enuresis will be screened at Shanghai Children's Medical Center, and those meeting eligibility criteria will be enrolled. Participants will be randomized to the Bladder Training Only Group, which will receive a 6-month intervention comprising fluid intake restriction, micturition desire-relaxation training, and sphincter control training.

Interventions

Circadian Rhythm Intervention Combined with Bladder Training

Participants diagnosed with primary nocturnal enuresis will be screened at Shanghai Children's Medical Center, and eligible patients will be enrolled. Participants will be randomly assigned to the Bladder Training Combined with Circadian Rhythm Intervention Group, which will receive a 6-month integrated protocol encompassing bladder training and circadian rhythm intervention. The bladder training component includes fluid intake restriction, micturition desire-relaxation training, and sphincter control training. Circadian rhythm interventions involve sleep hygiene education, chronotype-guided bedtime scheduling, and morning bright light therapy.

Intervention Type: BEHAVIORAL

Bladder Training (basic treatment for enuresis)

Participants diagnosed with primary nocturnal enuresis will be screened at Shanghai Children's Medical Center, and those meeting eligibility criteria will be enrolled. Participants will be randomized to the Bladder Training Only Group, which will receive a 6-month intervention comprising fluid intake restriction, micturition desire-relaxation training, and sphincter control training.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. Diagnosis according to the ICCS criteria:

At least one episode of involuntary nighttime urination per month for more than 3 months.

No abnormalities in routine urinalysis. No period of bedwetting-free days lasting more than 6 months, except for organic diseases.

2. Age: 5 to 15 years (inclusive), regardless of gender.

3. Right-handedness (as assessed by the Annett Hand Preference Questionnaire)

Exclusion Criteria

1. Secondary nocturnal enuresis;

2. History of head trauma, neurological disorders, psychosurgery, or major physical conditions (including autism spectrum disorder, epilepsy, cerebral palsy);

3. Contraindications to fMRI.

4. Note: Mild comorbidities commonly associated with primary nocturnal enuresis (e.g., ADHD) are permitted but must be included as covariates in statistical analyses.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Children's Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shanghai children's medical center

Shanghai, Shanghai Municipality, China

Countries

China

Central Contacts

Jun Ma, Doctor

Role: CONTACT

majun@shsmu.edu.cn

13917230745

Facility Contacts

Jun Ma, Doctor

Role: primary

majun@shsmu.edu.cn

13917230745

References

Austin PF, Bauer SB, Bower W, Chase J, Franco I, Hoebeke P, Rittig S, Vande Walle J, von Gontard A, Wright A, Yang SS, Neveus T. The standardization of terminology of lower urinary tract function in children and adolescents: update report from the Standardization Committee of the International Children's Continence Society. J Urol. 2014 Jun;191(6):1863-1865.e13. doi: 10.1016/j.juro.2014.01.110. Epub 2014 Feb 4.

Reference Type: BACKGROUND

PMID: 24508614 (View on PubMed)

Other Identifiers

2025-PWDL-13

Identifier Type: -

Identifier Source: org_study_id