EnuresisPhase 4NCT01861145
Intranasal Steroids for the Treatment of Nocturnal Enuresis With Associated Obstructive Sleep Apnea
A Phase 4 study testing Bed Alarm and Nasonex in people with Enuresis and Obstructive Sleep Apnea, run by University of Alberta at 2 sites in Canada.
Trial summary
Enuresis (E) or bedwetting is a common pediatric complaint, and recent research has discovered a link with obstructive sleep apnea (OSA). In children, OSA is often secondary to enlargement of their adenoids or tonsils, and is often successfully treated with a steroid solution given through the nose. Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Enuresis, Obstructive Sleep Apnea, Sleep Disordered Breathing
- What is being tested?
- Bed Alarm and Nasonex
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesCanada
- Study dates
- May 2013to Jun 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Ages between 5-17
- endorse 5/6 questions on the PSQ-22. These questions include: While sleeping, does your child: Ever snore? Snore more than half the time? Always snore? Snore loudly? Have "heavy" or loud breathing? Have trouble breathing, or struggle to breath?
- desire to use the bed alarm
Who cannot join
- Children <5
- known neurological disorders resulting in neuropathic bowel or bladder disorder including, but not limited to spinal dysraphisms and spinal cord injuries.
- significant congenital bladder anomalies, such as bladder exstrophy or posterior urethral valves
- patients with craniofacial anomalies or syndromes known to be associated with obstructive sleep apnea (i.e. Trisomy 21, muccopolysaccardiosis)
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Stollery Children's Hospital
Edmonton, Alberta, T6G 2B7
Synergy Respiratory Care Centre
Sherwood Park, Alberta, T8H 0N2
About this study
Enuresis (E) or bedwetting is a common pediatric complaint, and recent research has discovered a link with obstructive sleep apnea (OSA). In children, OSA is often secondary to enlargement of their adenoids or tonsils, and is often successfully treated with a steroid solution given through the nose.
The relationship between SDB and E is incompletely understood. Airway obstruction affects the quality of sleep, as the child will wake as the oxygen levels drop. Abnormal sleep also can decrease the secretion of hormones that affects the kidney's ability to concentrate urine at night, which can result in too much urine in the bladder. Contemporary evidence also suggests that patients with enuresis have abnormal sleep phases, which may impair the communications and inhibition of the bladder.
Read more
In previous studies, the investigators have demonstrated that children with E have a high likelihood of having concomitant SDB. The investigators have also demonstrated that children with E and symptoms of SDB do not respond to typical management for bedwetting. Therefore, the investigators propose to treat patients presenting with E with our standard treatments for E (bed alarm) and first line therapy for SDB: Intranasal steroids. This medication helps to decrease the inflammation of the adenoids and tonsils, thereby reducing the airway obstruction. the investigators hypothesize that children with significant symptoms of SDB will improve with the addition of INS, and the investigators hope to see an improvement in their bedwetting, quality of life, and sleep quality as well.
To test this, patents with E will be recruited from the pediatric urology clinic. They will be offered the standard treatment for E, the bed alarm, and the treatment group will be given an intranasal steroid spray. The investigators will then reassess the patients 3 months after treatment, and compare the two groups.
Read the detailed description
Enuresis (E) is a common pediatric urological complaint. Up to 15% of 5-year old children and 5% of 10-year old children are affected. Despite its prevalence, E is often ineffectively managed. Current treatment modalities include behavior modification, alarm therapy, and pharmacologic treatment. Recently, a significant amount of contemporary research has focused on sleep-disordered breathing (SDB) and its relation to E. This term encompasses a variety of disorders characterized by abnormalities of respiratory pattern or the quantity of ventilation during sleep. Often symptoms of OSA in children may be insidious in nature, and include behavioural problems, hyperactivity, poor school performance, failure to thrive and enuresis.
The relationship between E and OSA has only recently been questioned. Cinar et al. demonstrated 63% complete resolution and 4% partial resolution of E post surgical treatment of upper airway obstruction. Basha et al. had a similar result, with 61.4% of patients having total resolution of NE. The investigators have previously published results on the incidence of SDB in the enuretic population. Using the OSA-18 and PSQ-22 as screening tools for the symptoms of SDB, the investigators found that a significant proportion of patients with enuresis have SDB and the risk is further magnified in patients with abnormal daytime voiding.
The pathophysiology of this relationship is currently under review. With cystometrography, Brooks et al. demonstrated an increase in bladder pressure from 5 to 60 cm H2O with increasing respiratory efforts. Mahler et al. demonstrated that in healthy children exposed to sleep deprivation, disruption in the circadian rhythm resulted in a 68% increase in urine volume, a significant increase in sodium excretion, clearance, and fractional excretion. Sleep deprivation also resulted in higher nighttime blood pressure, and heart rate, which affected sodium regulating hormones, including the renin-angiotension-aldosterone system and ANP. Apneic episodes result in similar fluctuations in sodium excretion, by causing an increase in intrathoracic pressure, increased stretch of the cardiomyocytes, and excretion of atrial and brain natriuretic peptides. Finally, the overall disruption in sleep due to SDB may be the ultimate factor. Healthy children with sleep deprivation demonstrated increased naturiesis, and Yeung et al. demonstration that children with E have abnormal sleep EEG activity with impaired arousability, increased light non-REM sleep, frequent cortical arousals, and impaired wakening.
Enuresis is difficult to treat, and conventional modalities rarely achieve success rates greater than 65%. According to several systematic reviews, enuresis alarms have the highest efficacy rate, and result in an increase in the number of dry nights per week by 4. In a study by Monda et al., 66% of children using enuresis alarms achieved continence by 6 months. Alarms may also reduce treatment failure and relapse that is often associated with the use of medications such as tricyclic antidepressants. Enuresis alarms use a moisture sensor that activates as soon as the child begins to void.
In children, SDB is primarily caused by adenotonsillar hypertrophy, and treatment for OSA begins with a three-month trial of intranasal steroids (INS). INS act by directly reducing adenoidal size by lympholytic action, reducing inflammation, and decreasing the significance of adenoids as a reservoir for infection. In a recent meta-analysis, INS were found to reduce the symptoms of snoring, mouth breathing, and nasal speech by 45-50% when compared to placebo. Similarly, Demirhan et al. showed a mean decrease of adenoid/choana ratio from 86.9% to 56.2% after 8 weeks of fluticasone. In a recent meta-analysis, Zhang et al. found that 5/6 trials showed a significant improvement in nasal obstruction symptoms and reduction in adenoid size with the use of INS.
The investigators' previous data has shown that children with symptoms of SDB and E do not respond to conventional management of E. The investigators therefore propose to trial a novel management approach, by treating the symptoms of SDB with intranasal steroids, in hopes of improving patient's enuresis.
- Being tested
- Bed Alarm, Nasonex
- Keywords
- Intranasal steroids
- Medical subject headings
- Enuresis, Sleep Apnea, Obstructive, Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bed AlarmDevice
Also called Enuresis Alarm
The bed alarm is a device that is worn at night with a sensor in the child's underwear. The alarm will activate when the child urinates, helping the brain to link the sensation of a full bladder with wakening.
NasonexDrug
Also called Mometasone Furoate Aqueous Nasal Spray
Intranasal steroids are used by otolaryngologists as first line treatment for adenotonsillar hypertrophy in children with suspected sleep-disordered breathing and obstructive sleep apnea. The spray helps to shrink the size of the adenoids and tonsils, diminishing the amount of tissue obstructing the child's airway.
| Study group | Role | What they receive |
|---|---|---|
| Bed Alarm | Active comparator | Patients in the control arm will use only the bed alarm for treatment of their enuresis Receives: Device: Bed Alarm |
| Bed alarm + intranasal steroids | Experimental | Intervention: Nasonex (Mometasone furoate aqueous nasal spray) Children 5-11: 50 mcg/metered spray, 1 sprays in each nostril daily for 3 months in conjunction with nightly use of the bed alarm.
Children ≥ 12: 50 mcg/metered spray, 2 sprays in each nostril daily for 3 months in conjunction with nightly use of the bed alarm. Receives: Device: Bed Alarm; Drug: Nasonex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of improvement in enuresis after a 3 month trial of INS + bed alarm, compared to the bed alarm alone.
Measured: 3 months
Secondary outcomes (3)
Changes in OSA-18 and PSQ-22 scores after 3 month trial of INS
Measured: 3 months
Adverse effects related to treatments
Measured: 3 months
Patient related differences ie obesity, age, sex, and the effect on continence/treatment
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2013 (estimated)
- Study startMay 2013
- Primary completionDec 2015 (estimated)
- Study completionJun 2016 (estimated)
Why it stopped: Unable to sufficiently enroll or collect follow-up
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EnuresisStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Metcalfe, University of Alberta
- Investigators
- Peter Metcalfe, MD, Principal investigator, Stollery Children's Hospital and the University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01861145
- Sponsor's protocol ID
- Pro00032936
- Status last verified
- Dec 2015
- First submitted
- 21 May 2013
- Last updated
- 18 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intranasal Steroids for the Treatment of Nocturnal Enuresis With Associated Obstructive Sleep Apnea
- ClinicalTrials.gov ID
- NCT01861145
- Acronym / sponsor ID
- Pro00032936
- Keywords
- Intranasal steroids
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to sufficiently enroll or collect follow-up
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- May 2013
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Jun 2016 (estimated)
- First posted
- 23 May 2013 (estimated)
- 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.
Enuresis (E) or bedwetting is a common pediatric complaint, and recent research has discovered a link with obstructive sleep apnea (OSA). In children, OSA is often secondary to enlargement of their adenoids or tonsils, and is often successfully treated with a steroid solution given through the nose.
The relationship between SDB and E is incompletely understood. Airway obstruction affects the quality of sleep, as the child will wake as the oxygen levels drop. Abnormal sleep also can decrease the secretion of hormones that affects the kidney's ability to concentrate urine at night, which can result in too much urine in the bladder. Contemporary evidence also suggests that patients with enuresis have abnormal sleep phases, which may impair the communications and inhibition of the bladder.
In previous studies, the investigators have demonstrated that children with E have a high likelihood of having concomitant SDB. The investigators have also demonstrated that children with E and symptoms of SDB do not respond to typical management for bedwetting. Therefore, the investigators propose to treat patients presenting with E with our standard treatments for E (bed alarm) and first line therapy for SDB: Intranasal steroids. This medication helps to decrease the inflammation of the adenoids and tonsils, thereby reducing the airway obstruction. the investigators hypothesize that children with significant symptoms of SDB will improve with the addition of INS, and the investigators hope to see an improvement in their bedwetting, quality of life, and sleep quality as well.
To test this, patents with E will be recruited from the pediatric urology clinic. They will be offered the standard treatment for E, the bed alarm, and the treatment group will be given an intranasal steroid spray. The investigators will then reassess the patients 3 months after treatment, and compare the two groups.
Detailed description
Enuresis (E) is a common pediatric urological complaint. Up to 15% of 5-year old children and 5% of 10-year old children are affected. Despite its prevalence, E is often ineffectively managed. Current treatment modalities include behavior modification, alarm therapy, and pharmacologic treatment. Recently, a significant amount of contemporary research has focused on sleep-disordered breathing (SDB) and its relation to E. This term encompasses a variety of disorders characterized by abnormalities of respiratory pattern or the quantity of ventilation during sleep. Often symptoms of OSA in children may be insidious in nature, and include behavioural problems, hyperactivity, poor school performance, failure to thrive and enuresis.
The relationship between E and OSA has only recently been questioned. Cinar et al. demonstrated 63% complete resolution and 4% partial resolution of E post surgical treatment of upper airway obstruction. Basha et al. had a similar result, with 61.4% of patients having total resolution of NE. The investigators have previously published results on the incidence of SDB in the enuretic population. Using the OSA-18 and PSQ-22 as screening tools for the symptoms of SDB, the investigators found that a significant proportion of patients with enuresis have SDB and the risk is further magnified in patients with abnormal daytime voiding.
The pathophysiology of this relationship is currently under review. With cystometrography, Brooks et al. demonstrated an increase in bladder pressure from 5 to 60 cm H2O with increasing respiratory efforts. Mahler et al. demonstrated that in healthy children exposed to sleep deprivation, disruption in the circadian rhythm resulted in a 68% increase in urine volume, a significant increase in sodium excretion, clearance, and fractional excretion. Sleep deprivation also resulted in higher nighttime blood pressure, and heart rate, which affected sodium regulating hormones, including the renin-angiotension-aldosterone system and ANP. Apneic episodes result in similar fluctuations in sodium excretion, by causing an increase in intrathoracic pressure, increased stretch of the cardiomyocytes, and excretion of atrial and brain natriuretic peptides. Finally, the overall disruption in sleep due to SDB may be the ultimate factor. Healthy children with sleep deprivation demonstrated increased naturiesis, and Yeung et al. demonstration that children with E have abnormal sleep EEG activity with impaired arousability, increased light non-REM sleep, frequent cortical arousals, and impaired wakening.
Enuresis is difficult to treat, and conventional modalities rarely achieve success rates greater than 65%. According to several systematic reviews, enuresis alarms have the highest efficacy rate, and result in an increase in the number of dry nights per week by 4. In a study by Monda et al., 66% of children using enuresis alarms achieved continence by 6 months. Alarms may also reduce treatment failure and relapse that is often associated with the use of medications such as tricyclic antidepressants. Enuresis alarms use a moisture sensor that activates as soon as the child begins to void.
In children, SDB is primarily caused by adenotonsillar hypertrophy, and treatment for OSA begins with a three-month trial of intranasal steroids (INS). INS act by directly reducing adenoidal size by lympholytic action, reducing inflammation, and decreasing the significance of adenoids as a reservoir for infection. In a recent meta-analysis, INS were found to reduce the symptoms of snoring, mouth breathing, and nasal speech by 45-50% when compared to placebo. Similarly, Demirhan et al. showed a mean decrease of adenoid/choana ratio from 86.9% to 56.2% after 8 weeks of fluticasone. In a recent meta-analysis, Zhang et al. found that 5/6 trials showed a significant improvement in nasal obstruction symptoms and reduction in adenoid size with the use of INS.
The investigators' previous data has shown that children with symptoms of SDB and E do not respond to conventional management of E. The investigators therefore propose to trial a novel management approach, by treating the symptoms of SDB with intranasal steroids, in hopes of improving patient's enuresis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bed Alarm | Active comparator | Device: Bed AlarmPatients in the control arm will use only the bed alarm for treatment of their enuresis |
| Bed alarm + intranasal steroids | Experimental | Device: Bed Alarm, Drug: NasonexIntervention: Nasonex (Mometasone furoate aqueous nasal spray) Children 5-11: 50 mcg/metered spray, 1 sprays in each nostril daily for 3 months in conjunction with nightly use of the bed alarm. Children ≥ 12: 50 mcg/metered spray, 2 sprays in each nostril daily for 3 months in conjunction with nightly use of the bed alarm. |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Ages between 5-17
- endorse 5/6 questions on the PSQ-22. These questions include: While sleeping, does your child: Ever snore? Snore more than half the time? Always snore? Snore loudly? Have "heavy" or loud breathing? Have trouble breathing, or struggle to breath?
- desire to use the bed alarm
Key exclusion criteria (4 listed)
- Children <5
- known neurological disorders resulting in neuropathic bowel or bladder disorder including, but not limited to spinal dysraphisms and spinal cord injuries.
- significant congenital bladder anomalies, such as bladder exstrophy or posterior urethral valves
- patients with craniofacial anomalies or syndromes known to be associated with obstructive sleep apnea (i.e. Trisomy 21, muccopolysaccardiosis)
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 |
|---|---|---|
| Bed AlarmAlso: Enuresis AlarmThe bed alarm is a device that is worn at night with a sensor in the child's underwear. The alarm will activate when the child urinates, helping the brain to link the sensation of a full bladder with wakening. | Device | Bed Alarm, Bed alarm + intranasal steroids |
| NasonexAlso: Mometasone Furoate Aqueous Nasal SprayIntranasal steroids are used by otolaryngologists as first line treatment for adenotonsillar hypertrophy in children with suspected sleep-disordered breathing and obstructive sleep apnea. The spray helps to shrink the size of the adenoids and tonsils, diminishing the amount of tissue obstructing the child's airway. | Drug | Bed alarm + intranasal steroids |
Primary outcome
Degree of improvement in enuresis after a 3 month trial of INS + bed alarm, compared to the bed alarm alone.
Time frame: 3 months
3 secondary outcomes
Changes in OSA-18 and PSQ-22 scores after 3 month trial of INS
Time frame: 3 months
Adverse effects related to treatments
Time frame: 3 months
Patient related differences ie obesity, age, sex, and the effect on continence/treatment
Time frame: 3 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2015.
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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. This study is not recruiting at the moment.
Peter Metcalfe, MD principal investigator
Stollery Children's Hospital and the University of Alberta
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bed Alarm and Nasonex in people with Enuresis and Obstructive Sleep Apnea, run by University of Alberta at 2 sites in Canada.
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 3 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: withdrawn, as of the sponsor's last update on 18 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Degree of improvement in enuresis after a 3 month trial of INS + bed alarm, compared to the bed alarm alone. (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Dec 2015.