Primary Nocturnal EnuresisNCT07003126
A Cohort Study on Treating Primary Nocturnal Enuresis by Regulating Central-Peripheral Circadian Rhythm
A study testing Circadian Rhythm Intervention Combined with Bladder Training and Bladder Training (basic treatment for enuresis) in people with Primary Nocturnal Enuresis, run by Shanghai Children's Medical Center at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 15 years
- Conditions the study is for
- Primary Nocturnal Enuresis
- What is being tested?
- Circadian Rhythm Intervention Combined with Bladder Training and Bladder Training (basic treatment for enuresis)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2025to 1 Jun 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Shanghai children's medical center
Shanghai, Shanghai Municipality, 200127
Jun Ma, Doctor, 13917230745, majun@shsmu.edu.cn
About this study
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.
Read the 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
- Being tested
- Circadian Rhythm Intervention Combined with Bladder Training, Bladder Training (basic treatment for enuresis)
- Keywords
- Primary Nocturnal Enuresis, Circadian Rhythm, Treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Circadian Rhythm Intervention Combined with Bladder TrainingBehavioural
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)Behavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Behavioral: Bladder Training (basic treatment for enuresis) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From enrollment to the end of treatment at 6 months
Secondary outcomes (7)
Resting-State Functional Magnetic Resonance Imaging (fMRI) Data
Resting-state fMRI data will be acquired to characterize brain functional networks, with a focus on analyzing functional connectivity between the suprachiasmatic nucleus and superior temporal gyrus.
Measured: From enrollment to the end of treatment at 6 months
Diurnal and Nocturnal Urine Volume
Participants will complete at least one 24-hour fluid intake and voiding diary per week, including diurnal and nocturnal urine volume recorded pre-treatment, during treatment, and post-treatment.
Daytime voiding will be measured using graduated plastic cylinders for each urination. Nocturnal voiding will be recorded by wearing pre-weighed diapers (with urine volume calculated by weighing the diapers the next day) or through timed voiding upon waking during the night.
The average total diurnal and nocturnal urine volume during each recorded period will be calculated as the participant's diurnal and nocturnal urine volume at different time points.
Measured: From enrollment to the end of treatment at 6 months
Heart Rate Variability
Continuous measurement of beat-to-beat intervals assessed via research-grade wearable actigraphy, using artificial intelligence-driven chronobiological analytics to extract features.
Unit of Measure: Milliseconds
Measured: From enrollment to the end of treatment at 6 months
Polysomnography-Validated Sleep Metrics
Sleep efficiency validated against polysomnography benchmarks and derived from wearable actigraphy data streams.
Unit of Measure: Percent (%)
Measured: From enrollment to the end of treatment at 6 months
Grade scoring of the micturition desire-awakening function
The grade scoring of the micturition desire-awakening function based on the average awakening ability each night. The grade scoring of the micturition desire-awakening function is as follows:
Grade 5: Remains asleep most of the time after urination. Grade 4: Only awakens after completely wetting the bed. Grade 3: Awakens only after urinating a significant amount and then goes to the toilet to void the remaining urine.
Grade 2: Awakens after urinating a small amount and then goes to the toilet to void the remaining urine.
Grade 1: Awakened by the urge to urinate, without wetting the bed.
Measured: From enrollment to the end of treatment at 6 months
Standardized Bladder Capacity
Standardized bladder capacity = bladder capacity/body surface area. Compare the standardized mean bladder capacity as well as the maximum and minimum daytime/nighttime bladder capacity changes from baseline to 6 months.
The term mean daytime bladder capacity refers to the average volume of voided urine measured on the frequency volume chart throughout a 24-hour cycle.
The term maximum/minimum daytime bladder capacity refers to the largest/smallest volume of voided urine measured on the frequency volume chart during the day. It excludes the first morning void.
The term maximum/minimum nighttime bladder capacity refers to the largest/smallest volume of voided urine measured on the frequency volume chart during the night. It includes the first morning void.
Measured: From enrollment to the end of treatment at 6 months
Salivary Melatonin Levels
Saliva samples (2 mL each) will be collected from children with PNE at 4-hour intervals starting at 09:00, yielding seven timepoints (09:00, 13:00, 17:00, 21:00, 01:00, 05:00, and 09:00 the following day) within a ±1-hour window. Collections at 21:00, 01:00, and 05:00 will be performed under dim-light conditions (ambient illumination <30 lux).
Salivary melatonin concentrations will be quantified using liquid chromatography-tandem mass spectrometry-a rapid, sensitive, and reliable method validated for low-abundance hormone detection in saliva.
Measured: From enrollment to the end of treatment at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2025
- Study start1 Jul 2025 (estimated)
- Primary completion30 Dec 2027 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Nocturnal EnuresisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Children's Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07003126
- Sponsor's protocol ID
- 2025-PWDL-13
- Status last verified
- May 2025
- First submitted
- 25 May 2025
- Last updated
- 4 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24508614
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cohort Study on Treating Primary Nocturnal Enuresis by Regulating Central-Peripheral Circadian Rhythm
- ClinicalTrials.gov ID
- NCT07003126
- Acronym / sponsor ID
- 2025-PWDL-13
- Conditions
- Primary Nocturnal Enuresis
- Keywords
- Primary Nocturnal Enuresis, Circadian Rhythm, Treatment
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Shanghai Children's Medical CenterUniversity, hospital or other
- Study start
- 1 Jul 2025 (estimated)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 4 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Circadian Rhythm Intervention Combined with Bladder Training | Experimental | Behavioral: Circadian Rhythm Intervention Combined with Bladder TrainingThe 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. |
| Bladder Training (basic treatment for enuresis) | Active comparator | Behavioral: 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. |
Who may qualify
- Ages
- 5 to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Circadian Rhythm Intervention Combined with Bladder TrainingParticipants 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. | Behavioural | Circadian Rhythm Intervention Combined with Bladder Training |
| 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. | Behavioural | Bladder Training (basic treatment for enuresis) |
Primary outcome
Enuresis Improvement Rate
Time frame: From enrollment to the end of treatment at 6 months
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.
7 secondary outcomes
Resting-State Functional Magnetic Resonance Imaging (fMRI) Data
Time frame: From enrollment to the end of treatment at 6 months
Diurnal and Nocturnal Urine Volume
Time frame: From enrollment to the end of treatment at 6 months
Heart Rate Variability
Time frame: From enrollment to the end of treatment at 6 months
Polysomnography-Validated Sleep Metrics
Time frame: From enrollment to the end of treatment at 6 months
Grade scoring of the micturition desire-awakening function
Time frame: From enrollment to the end of treatment at 6 months
Standardized Bladder Capacity
Time frame: From enrollment to the end of treatment at 6 months
Salivary Melatonin Levels
Time frame: From enrollment to the end of treatment at 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
- Background: PubMed 24508614Austin 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Circadian Rhythm Intervention Combined with Bladder Training and Bladder Training (basic treatment for enuresis) in people with Primary Nocturnal Enuresis, run by Shanghai Children's Medical Center at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jun Ma, Doctor (13917230745, majun@shsmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Enuresis Improvement Rate (time frame: From enrollment to the end of treatment at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07003126, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2025.