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

NCT07003126 | Not Yet Recruiting

• 1 other identifier: 2025-PWDL-13
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Nocturnal Enuresis

Keywords

Primary Nocturnal Enuresis; Circadian Rhythm; Treatment

Outcome Measures

Primary Outcomes (1)

• Enuresis Improvement Rate

  The enuresis improvement rate is the sum of the complete and partial response rates. No response: \<50% reduction. Partial response: 50 to 99% reduction. Complete response: 100% reduction.

  From enrollment to the end of treatment at 6 months

Secondary Outcomes (7)

• Resting-State Functional Magnetic Resonance Imaging (fMRI) Data

  From enrollment to the end of treatment at 6 months

• Diurnal and Nocturnal Urine Volume

  From enrollment to the end of treatment at 6 months

• Heart Rate Variability

  From enrollment to the end of treatment at 6 months

• Polysomnography-Validated Sleep Metrics

  From enrollment to the end of treatment at 6 months

• Grade scoring of the micturition desire-awakening function

  From enrollment to the end of treatment at 6 months

Study Arms (2)

Circadian Rhythm Intervention Combined with Bladder Training

EXPERIMENTAL

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.

Behavioral: Circadian Rhythm Intervention Combined with Bladder Training

Bladder Training (basic treatment for enuresis)

ACTIVE COMPARATOR

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.

Behavioral: Bladder Training (basic treatment for enuresis)

Interventions

Circadian Rhythm Intervention Combined with Bladder Training 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.

Circadian Rhythm Intervention Combined with Bladder Training

Bladder Training (basic treatment for enuresis) 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.

Bladder Training (basic treatment for enuresis)

Eligibility Criteria

• Age: 5 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Age: 5 to 15 years (inclusive), regardless of gender.
• Right-handedness (as assessed by the Annett Hand Preference Questionnaire)

You may not qualify if:

• Secondary nocturnal enuresis;
• History of head trauma, neurological disorders, psychosurgery, or major physical conditions (including autism spectrum disorder, epilepsy, cerebral palsy);
• Contraindications to fMRI.
• Note: Mild comorbidities commonly associated with primary nocturnal enuresis (e.g., ADHD) are permitted but must be included as covariates in statistical analyses.

Sponsors & Collaborators

• Shanghai Children's Medical Center: lead

Study Sites (1)

Shanghai children's medical center

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (1)

• 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.

  PMID: 24508614 BACKGROUND

Central Study Contacts

Jun Ma, Doctor

CONTACT

13917230745; majun@shsmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2025
• First Posted: June 4, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)