Scheduled Awakenings for the Treatment of Nocturnal Enuresis
Phase: NA
Conditions: Nocturnal Enuresis
Sponsor: Indiana University

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Scheduled Awakenings for the Treatment of Nocturnal Enuresis 
   
Benjamin Whittam, M.D., M.S., Pediatric Urology  
Riley Hospital for Children  
705 Riley Hospital Dr., Suite 4230 
Indianapolis, IN 46202 
  
  
NCT Number:  1601620278 
 
  
  
  
  
  
  
  
  
  
  
Sub-Investigators: 
Shelly King, C.P.N.P., Pediatric Urology/ Riley Hospital for Children 
Adam Rensing M.D., Depart of Urology 
Konrad Szymanski, M.D., MPH., Pediatric Urology/Riley Hospital for Children 
William Bennett, M.D., Pediatric and Adolescent Comparative Effectiveness Research 
  
  
  
  
  
  
  

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Table of Contents: 
  
Study Schema 
1.0          Background 
2.0          Rationale and Specific Aims 
3.0          Inclusion/Exclusion Criteria 
4.0          Enrollment/ 
5.0          Study Procedures 
6.0          Reporting of Adverse Events or Unanticipated Problems involving Risk to 
Participants or Others 
7.0          Study Withdrawal/Discontinuation 
8.0          Statistical Considerations 
9.0          Privacy/Confidentiality Issues 
10.0   
Follow-up and Record Retention 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.0          Background  
 
Primary monosymptomatic  nocturnal enuresis (PMNE) is defined by the Diagnostic & Statistical 
Manual of Mental Disorders (DSM- IV) as an involuntary voiding of urine during sleep, with a 
severity of at least twice a week, in children aged >5 years in the absence of congenital or 
acquired  defects of the central nervous system(1-3). Other etiologies that cause bed wetting 
such as cardiopulmonary, neurologic, endocrine or urologic diseases should be ruled out (1). 
Secondary nocturnal enuresis is defined nocturnal enuresis after at least 6 month of continuous 
dryness without prior without intervention (1, 4).  
 
PMNE affects 10-20% kids at 5 years old (1, 4, 5). It does resolve spontaneously so that 5% of 
10 year olds and 1% of 15 year olds are still affected (2-4). Is more common in boys. While the 
disease its self is benign, and improves without intervention, it does pose a significant social 
and emotional burden on the child and their family. These include parental disapproval, sibling 
teasing, and inability to attend sleep overs with peers, all of which lead to families seeking 
treatment options (3, 4).   
 
Current treatments start with conservative management. This includes appropriate fluid intake, 
scheduled toileting during the day, avoidance of bladder irritants and constipation (4, 5). If these 
fail to improve symptoms or families are looking for a more active form of treatment, first line 
therapy is either a bed wetting alarms or desmopressin (1, 4, 5).  
 
Bed wetting alarms typically attach to the child’s clothes and sound when the device gets wet 
with urine. The goal of these devices is to alert the child that he or she has started to urinate 
and to allow them to be woken up, then voluntarily complete the void in the bathroom (1, 3, 6). 
While these devices are effective, they take about 4 weeks of constant use to show significant 
improvement and require continued use for at least 3 months to gain durable results (2, 5, 6). 
Alarms also suffer from a high discontinuation rate, as high as 30% (2, 3, 6). Problems 
associate with disruption of other family members, difficulty using the devices, and the device 
failing to cure PMNE have all been cited by families and reasons they stopped using the device 
(3, 6).  
 
Desmopressin works as a vasopressin analogue to decrease urine production at night (1, 2, 4). 
It is quicker to improve symptoms compared to alarms once the treatment is discontinued the 
recurrence of PMNE is significantly higher than alarm devices (2, 4, 6).  
 
The Lully Sleep Guardian was initially developed for use in night terrors. The device works by 
programing a vibrating disk that is placed under the child’s bed to alter sleep patterns and 
prevent the onset of sleep terrors. The child is not woken up for the treatment of sleep terrors. 
The device has also be shown to anecdotally improve users’ nocturnal enuresis. There have 
been no reports of safety concerns or hazards with the device (7, 8).  
 
  
 
2.0          Rationale and Specific Aims 
  
Aim 1: Determine the effectiveness of scheduled awakenings, with the Lully Sleep Guardian, in 
patients with PMNE, at reducing the frequency of bed-wetting.  
 
  

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3.0          Inclusion/Exclusion Criteria 
 
Inclusion Criteria 
Exclusion Criteria 
• 
Benign nocturnal enuresis 
• 
Age: 5 – 17 
• 
Access to an Apple iPhone, IPad, or 
iPod Touch preferred.  (Will have a 
limited number if ipods available for 
loan if needed)  
 
 
 
● 
Diurnal Enuresis  
● 
Constipation 
● 
Neurogenic Bladder 
● 
Any serious underlying cardiopulmonary 
problems that require diuretics or 
antihypertensive medications to manage 
● 
Any bladder active medications 
● 
Age: < 5 years of age; > 17 years of age 
● 
Cerebral Palsy 
● 
Mental disorders, mood disorders, or 
autism-spectrum disorder 
● 
Epilepsy or seizure history 
● 
Restless leg syndrome 
● 
Use of benzodiazepine/clonidine 
        
 
 
4.0          Enrollment 
 
Patient Identification, Recruitment, Eligibility Determination 
 
Participants may be recruited from the pediatric urology clinic at Riley Hospital for Children. 
These patients may be established patients, new patients, or referrals to Pediatric Urology not 
yet seen in clinic.  We will also accept potential participants who are not affiliated with the 
Pediatric Urology clinic but meet inclusion criteria and have interest. These possible participants 
include those who attend bedwetting seminars conducted by Pediatric Urology and those who 
respond to advertising in the community. Potential participants may be recruited from the 
community through the use of flyers, social media, and INResearch 
 
The initial contact with potential participants may be in person, by phone, or by email. A 
research team member will provide an overview of the study and be available to answer any 
questions posed by the family and/or patient. If the family has ongoing interest, they will be 
asked to complete screening questions to determine if the child meets the eligibility criteria for 
this study. If a potential participant responds directly to the flyer, they have the option to answer 
eligibility questions before interaction with a study team member.  
 
To confirm potential participant does not meet any of the exclusion criteria and is eligible,  the 
parent and participant will be asked to together complete two screening questionnaires, the Lully 
Q &A and the Vancouver questionnaire . Questionnaire results will be reviewed by a study team 
member and eligibility will be determined. 
 
 
 

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Consent Procedures  
If the candidate is eligible, the informed consent,  the assent (if applicable) and the 
HIPAA authorization will be obtained to enroll the patient. Informed consent and 
authorization procedures may occur in person or via phone. In either circumstance, the 
research team member will obtain written signature of consent and authorization. For 
children 7 – 17 years old, we will obtain child assent in addition to parents informed 
consent. After consenting, the participant will be immediately assigned to a treatment 
arm. 
 
 
Treatment Arms  
 
This study will enroll a total of 40 patients, with 20 in each treatment  arm. 
 
The first 20 subjects enrolled are scheduled to complete the study phases (S1 and S2) in the 
following order:  6 weeks of behavioral modifications plus the Lully device, followed by 6 
weeks of behavioral modifications only (without the device).  Subsequently, the last 20 subjects 
enrolled will undergo the study phases in the reverse order:  6 weeks of behavioral modifications 
only, followed by 6 weeks of behavioral modifications plus use of the Lully device This 
crossover will increase the validity of findings, but also ensure ease and simplicity when 
following patients.  
 
The Lully device will be labelled in accordance with FDA investigational labelling requirements. 
 
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. 
 
5.0          Study Procedures 
 
During the initial and therapeutic phases of this study, participants are asked to enter responses 
daily into a Lully Study app. When the parent sets up the app, they enter their study email 
address, which is in the format iuenuresis16XX@lullysleep.com.  The app will send a prompt 
each morning.  The questions the participant is prompted to answer are: Did your child have a 
bed wetting episode last night? What time was it?  
 
In a free text box the family is asked to add additional information to describe how wet the child 
was using the following 1-5 scale: 1- wet underwear; 2-wet underwear and damp pajamas; 3-
soaked underwear, pajamas; 4-soaked pajamas, damp mattress; 5- soaked mattress 
 
 
Initial Phase to establish baseline( 4 wks) 
1. The family will complete a QOL survey, the KIDSCREEN 27 before starting the initial 4 
week phase. 
2.  The family will receive further counseling on behavioral modifications. Handout 
available for reference in Notes and Attachments.  

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3. Family will be provided with Malem Enuresis alarm to be used daily during 2 weeks of 
baseline data collection  
4. Family will be asked to complete the KIDSCREEN 27 and the Vancouver questionnaire 
before starting therapeutic phase 
. 
 
 
 
Therapeutic phase  
1. Each participant will complete the study phases (S1 and S2) in the order determined by 
their assigned treatment arm  
 
2. During the 6 weeks of scheduled awakening protocol using Lully Sleep Guardian: each 
night, a scheduled awakening will be performed with the Lully pod. This will be used to 
reliably produce a brief awakening by titrating the device to a minimal awakening 
stimulus during the first night of use. If the brief awakening cannot be produced using the 
Lully pod, the parent will gently awaken the child 
       3.   The family will complete the KIDSCREEN 27 and the Vancouver questionnaire at 
the cross-over between the study phases ( S1 and S2) and at the completion of their 2 
study phase 
 
Study Completion 
 
Family will be asked to return any equipment loaned for the purposes of this study to the 
Pediatric Urology Clinic at Riley 
  
 
 
 
 
 
 
 
 
 
 
 Compensation 
Patient and families will be compensated with $1 per day for each day they respond to the daily 
questions prompted by the app about their child’s nocturnal enuresis are replied to and an 
additional $5 per round of QOL surveys (2 surveys per round).  The total will be summed at the 
conclusion of the study and paid to the participant as an Amazon gift card. 
 
 
 
6.0          Reporting of Adverse Events or Unanticipated Problems involving Risk to 
Participants or Others 
 
Adverse events will be monitored by the PI and co-investigators. As the participants will be 
receiving clinical urology care and the interventions are minimal risk, physical adverse events 
related to the study are not expected.  Each event will be handled individually. Adverse events 
or unanticipated problems involving risk to the participants or others will be reported according 
to IRB standard operating procedures.  If the adverse event represents an unanticipated 
problem and requires changes to the research protocol or informed consent process/document 
or other corrective actions in order to protect the safety, welfare, or rights of subjects or others, it 
will be reported to the IRB using the Prompt Reporting Form within five business days of the 
investigator becoming aware of the event. Unless determined to not represent an unanticipated 
problem by HSO staff or the IRB Chair or Chair’s designee, the report will be reviewed at a 
convened IRB meeting for possible action.  Any serious unanticipated adverse events will be 
reported within 24 hours of becoming aware of the event.   

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7.0          Study Withdrawal/Discontinuation 
 
The principal investigator will terminate the involvement of a given participant in the research 
study if they request to stop participating. The criteria which would result in removal from the 
study are: participant request to withdraw from the study. The principal investigator reserves the 
right to withdraw a family from the study if they do not meet the study requirements.  Should this 
occur, the family will be notified by a member of the study team and paid for the activities they 
completed.  
 
8.0          Statistical Considerations 
  
This study is a simple effectiveness trial to determine if the Lully Sleep Guardian has any effect 
on benign nocturnal enuresis. If an effect is shown, the research team will use this study to 
perform a power calculation and facilitate a comparative effectiveness trial comparing Lully 
Sleep Guardian to current standards of care. 
  
9.0          Privacy/Confidentiality Issues 
  
 
Research material obtained from living human subjects will include medical records, with 
medical information collected by the PI/Research Nurse during screening/study visits; and data 
collected from the questionnaires and interviews. 
 
All paper records containing identifying information will be kept in locked files accessible only to 
study staff and unlocked only while a study staff member is physically present.  All computer 
records will require password access; computer workstations will be locked whenever a staff 
person leaves his or her desk.  
 
10.0      Follow-up and Record Retention 
  
Timeframe 
Activity 
Y1 Quarter 1 
Y1 Quarter 2 
Y1 Quarter 3 
Y1 Quarter 4 
Study run-up and information to clinicians 
and schedulers 
 
 
 
 
Training on device 
 
 
 
 
 
Actively enroll patients 
 
 
 
 
 
Data Analysis and Dissemination 
 
 
 
 
 
 
Record Retention 

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The duration of record retention will be at least seven years after the study has ended.  Should 
the parent/guardian or child decide to withdraw from study participation, the participant’s name 
will be removed from the excel datasheet where it had been recorded and the records will be 
destroyed. 
 
 
 
References: 
1. 
National Clinical Guideline C. National Institute for Health and Clinical Excellence: Guidance.  
Nocturnal Enuresis: The Management of Bedwetting in Children and Young People. London: Royal 
College of Physicians (UK) National Clinical Guideline Centre.; 2010. 
2. 
Ahmed AF, Amin MM, Ali MM, Shalaby EA. Efficacy of an enuresis alarm, desmopressin, and 
combination therapy in the treatment of saudi children with primary monosymptomatic nocturnal 
enuresis. Korean journal of urology. 2013;54(11):783-90. 
3. 
Glazener CM, Evans JH, Peto RE. Alarm interventions for nocturnal enuresis in children. The 
Cochrane database of systematic reviews. 2005(2):Cd002911. 
4. 
Bayne AP, Skoog SJ. Nocturnal enuresis: an approach to assessment and treatment. Pediatrics in 
review / American Academy of Pediatrics. 2014;35(8):327-34; quiz 35. 
5. 
Monda JM, Husmann DA. Primary nocturnal enuresis: a comparison among observation, 
imipramine, desmopressin acetate and bed-wetting alarm systems. The Journal of urology. 1995;154(2 
Pt 2):745-8. 
6. 
Onol FF, Guzel R, Tahra A, Kaya C, Boylu U. Comparison of long-term efficacy of desmopressin 
lyophilisate and enuretic alarm for monosymptomatic enuresis and assessment of predictive factors for 
success: a randomized prospective trial. The Journal of urology. 2015;193(2):655-61. 
7. 
Rink A. Lully Sleep Guardian. In: Heinsimer K, editor. IU Health2016. 
8. 
Lully Sleep Guardian - Proven to Stop Night Terrors: Amazon; 2016 [cited 2015 2016]. Available 
from: http://www.amazon.com/Lully-Sleep-Guardian-Proven-
Terrors/dp/B011LOUNCI/ref=sr_1_1?ie=UTF8&qid=1457660065&sr=8-1-
spons&keywords=lully+sleep+guardian&psc=1#customerReviews.