Telehealth Delivery of Treatment for Sleep Disturbances in Young Children With Autism Spectrum Disorder
Phase: NA
Conditions: Autism Spectrum Disorder, Sleep Disturbance
Sponsor: The Cleveland Clinic

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Protocol Title:  Telehealth Delivery of Treatment for Sleep Disturbances in 
Young Children with Autism Spectrum Disorder 
 
Funding:  Department of Defense 
 
Principal Investigator:  Cynthia Johnson, PhD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Background 
 
ASD is a Major Health Problem in Need of Evidenced-Based Treatments.   
Current estimates of the prevalence of ASD range from 6.2 to 14.7 per 1000.1,2 In addition to the core features 
of ASD (social communication deficits; repetitive and restrictive behaviors), as many as 70% of children with 
ASD have additional problems such as hyperactivity, disruptive behavior, and anxiety severe enough to warrant 
treatment.3-8  An estimated 44 to 80% of children with ASD also have sleep disturbances.9-12 This wide range 
reflects differences in the source of sample, assessment methods and severity level (mild to severe). The 
estimate of 80% likely includes children with mild sleep disturbance. Children with ASD and moderate or 
greater levels of severity require intervention.13 Providing appropriate treatment for children with ASD is a 
challenge to the service system, with current costs estimated to be $125 billion annually.14 Treatment 
approaches commonly used for core and associated features include behavior therapy,15-17 comprehensive 
educational interventions18,19 and pharmacotherapy.20,21 The heightened recognition and increased demand for 
services, however, occurs against a backdrop of insufficient evidence for many treatments.22-25 There is a 
pressing need to conduct well-designed studies to expand the portfolio of empirically supported, time-limited 
and cost-effective interventions to meet rising demand and guide clinical practice.26  
   According to the World Health Organization, a major obstacle for access to adequate services for children 
with disabilities is the lack of trained specialists.27 Although children with ASD account for 10–14% of those 
referred for mental health treatment, only 5% of mental health practitioners consider themselves prepared to 
treat children with ASD.28 Moreover, training in behavioral health programs on the assessment and treatment of 
pediatric sleep disturbances is limited.29 As a result, the demand for treatment of children with ASD and sleep 
disturbances far outpaces the availability of empirically supported interventions and skilled providers in the 
community. This lack of access often results in long waiting lists for services and families resorting to 
treatments without empirical support.30 In a randomized trial of 180 young children with ASD, we showed that 
parent training was superior to parent education for reducing disruptive behavior.31 This project will test 
whether telehealth delivered parent training for sleep problems is superior to parent education in children with 
ASD.   
 
Importance of Sleep. 
 Biological and environmental factors play a role in the development and maintenance/disruption of the sleep-
wake cycle. The hypothalamus controls the timing of sleep, body temperature and cortisol production. 
Melatonin (produced by the pineal gland) affects sleep-wake patterns via feedback between the pineal gland and 
hypothalamus. This hormone is suppressed by exposure to bright light. Factors such as light perception, social 
cues, ambient temperature, noise levels, and internal body signals (hunger, body temperature) also contribute to 
the sleep-wake rhythm.32 Sleep requirements vary by age: children 2 to 5 years require 11-13 hours of sleep per 
day; school-age children require 10-11 hours.33-37  
     Over fifty years of research attest to the critical need for adequate sleep. Sleep plays a central role in early 
brain maturation 38-40 and plasticity.41-47  Inadequate sleep in school-age children can impair cognitive functions 
such as working memory and abstract thinking,48-51 motor reaction time;52 attention,45,48,51,53-59 emotion 
regulation48,51,60-62 and academic functioning.54,57,63,64 Although limited, available evidence suggests a clear link 
between disrupted sleep and daytime behavior problems in young children.62,63,65 Sleep disturbances in young 
children may also have adverse effects on family functioning due to parental sleep deprivation.66-68  
 
Sleep, Mental Health & Physical Health.   
 Sleep disturbances are associated with several mental health disorders including anxiety, depression, attention 
deficit hyperactivity disorder (ADHD), post-traumatic stress, and bipolar disorder.69-75 Several studies show the 
common co-occurrence of sleep problems and emotional problems in children.74,76,77 Emerging data link sleep 
disruption to the onset of internalizing and externalizing problems in children.60,78,79 These findings have 
prompted a shift in treatment paradigms to address sleep difficulties alongside the emotional and behavioral 
problems or even as a first step in the treatment plan.75,80-82  Moreover, there are physical health implications for 

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chronic, inadequate sleep and poor sleep quality.83-85 Collectively, there is compelling evidence that 
intervening early on sleep disturbances in young children with ASD could offset a range of untoward events 
and maximize a child’s participation in early therapeutic and educational activities.   
 
Sleep Disturbances in Children with ASD.   
 The prevalence of sleep problems in the general pediatric population is estimated at 25%.86 By contrast, poorly 
regulated sleep patterns (trouble falling asleep, mid-sleep awakening and early morning awakening) affect as 
many as 80% of children with ASD regardless of cognitive functioning level.10,11,67,87-98 Although severity of 
sleep dysregulation in children with ASD varies from mild to severe, children with moderate or greater sleep 
problems require treatment to avert the associated adverse effects of inadequate sleep. Closely related problems 
for children with ASD include noncompliance with bedtime routines, difficulty establishing essential elements 
of sleep hygiene due to over-arousal and sleep-onset association problems (e.g., only able to fall asleep 
somewhere other than bed, requires certain objects or person to be present for sleep onset),12 resulting in overall 
lower sleep quality.99 
     Johnson10 long ago proposed that the core social communication deficits of ASD, and often co-occurring 
cognitive deficits, interfere with the child’s capacity for self-soothing.  Consequently, children with ASD may 
be less able to promote sleep onset independently or return to sleep upon waking after sleep onset.10 Children 
with ASD may also have difficulty understanding social and environmental cues that are part of the bedtime 
routine. Some children with ASD develop idiosyncratic bedtime routines that hinder sleep such as insisting on 
toys be arranged just so with attendant disruptive behavior that interferes with settling down.99 Co-occurring 
gastrointestinal problems, seizures, anxiety, depression, ADHD, or medication side-effects (e.g., stimulants, 
serotonin reuptake inhibitors) may also interfere with sleep patterns.90,100-106  Alteration in melatonin secretion 
in children with ASD may contribute to sleep disturbance.107,108 Several studies have reported markedly lower 
mean plasma melatonin levels and lower urinary excretion of melatonin sulfate (MEL-S, also known as 6-MEL-
S) in ASD compared to typically developing controls.109-111  In sum, disruptive behavior, elaborate bedtime 
routines, poor self-soothing and understanding of environmental cues, neurochemical alterations, and 
concurrent medical problems may interfere with developing a stable sleep-wake cycle in children with ASD. 
     Disordered sleep in children with ASD can amplify already delayed social interactions, repetitive behaviors, 
affective problems, inattention/hyperactivity, and irritability.88,112-117  Given the documented detrimental effects 
of sleep disturbance on cognition, attention, memory consolidation, and daytime behavioral adjustment, 
addressing sleep disturbances in young children with ASD may promote overall improvement and fuller use of 
educational and therapeutic interventions.  Sleep difficulties in children with ASD produce significant stress on 
caregivers and negative attitudes toward the child.88,118-120 Parents of children with ASD have poorer sleep 
quality than parents of typically developing children.121,122 Sleep problems in the child may contribute to lower 
quality of sleep in mothers,123 and are inversely correlated with maternal depressive symptoms.124 Interventions 
that improve sleep in the child may reduce parental stress and improve mood and overall health.    
 
Interventions for Sleep Disturbance in Children with ASD.   
 Supplemental melatonin, which is safe and inexpensive, has shown promise as a treatment for sleep onset delay 
in children with ASD.32,109,125-133 However, melatonin does not address behavioral bedtime resistance, teach 
self-soothing to promote sleep, and may not be helpful for night wakings.109,133 Not surprisingly, behavioral 
interventions for sleep disturbances remain first line treatments for insomnia in general pediatrics.134,135 
However, behavioral interventions for sleep disturbances in children with ASD have not been carefully studied. 
Ironically, surveys indicate that most parents of children with ASD favor behavioral approaches over sleep-
enhancing medications.120 Based on successful behavioral interventions for sleep onset and maintenance 
problems used in typically developing children, similar approaches have been used clinically in children with 
ASD with some success.96,135 Specific adaptations for children with ASD and other developmental disorders 
include establishment of routines, environmental modifications, placing sleep restrictions on the child, 
extinction procedures, and scheduled awakenings.136-146 The time is right to pursue a well designed randomized 
trial targeting sleep disturbances in children with ASD to guide clinical practice with the goal of optimizing the 
reach of the intervention via telehealth.  

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Behavioral Parent Training in ASD.  
Parents confront daily struggles in rearing a child with ASD. Sleep disturbances present yet another challenge. 
Parent training (PT) is a fitting treatment model for sleep problems in young children with ASD for several 
reasons: 1) the central role of parents in promoting the development of children with ASD; 2) the demonstrated 
feasibility of parent training in the treatment of sleep problems (see below); and 3) the negative impact of sleep 
disturbances on the child and family. To date, structured PT interventions have focused largely on child 
language, adaptive skills, joint attention and other social communication behaviors.147-150 There is a growing 
body of empirical support for the efficacy of PT in children with ASD and disruptive behavior.31,149-153 In two 
previous large-scale multi-site trials, we showed that PT was effective for reducing disruptive behavioral 
problems and improving daily living skills compared to parent education.31,154 Our PT program included one 
session on sleep problems, which was helpful for some children. For children with ASD and moderate to severe 
sleep problems, however, more intensive and focused treatment on sleep may be required.     
     In a review of 24 published studies on behavioral interventions that targeted sleep problems in children with 
ASD and other developmental disabilities, most studies were small case series or single subject design studies. 
These studies set the stage for a large RCT as the next step in keeping with the recommendations of an NIMH 
convened workgroup.155 To date, there have been only two large-scale RCTs of a behavioral intervention for 
sleep disturbances in children with ASD.143 Cortesi and colleagues156 compared the efficacy of 4 sessions of PT 
to PT plus melatonin (MLT), MLT alone and placebo in a sample of 160 4-10 year-olds with ASD. After 12 
weeks, all three active treatments showed superiority to placebo in sleep onset latency (SOL) and wakings after 
sleep onset on actigraphy and a parent completed questionnaire. There was a statistical trend favoring combined 
treatment. In a randomized sample of 80 children with ASD, ages 2-10 years with sleep onset problems, Malow 
and colleagues compared a single parent individual educational session to two group sessions. Both programs 
showed improvement in SOL and modest improvement in sleep efficiency on actigraph.157 Although these 
studies expand the evidence-base on sleep interventions for children with ASD, both have notable limitations. 
The four-group study by Cortesi et al.156 excluded children with behavioral problems, which limits 
generalizability. In addition, subjects whose treatment compliance fell below 80% (n=16) were excluded from 
the analysis. The Malow et al. study was brief and focused primarily on sleep latency. These studies were all 
delivered in a tertiary clinical setting.  These settings are limited to their access to families who may have to 
travel distances and may have long waiting lists. 
     Although prior research documents the high rate of moderate or greater sleep problems in children with ASD 
and the potentially detrimental effects, available evidence on intervention is encouraging but inconclusive. The 
time is right for an innovative telehealth trial of an exportable parent training intervention for sleep 
disturbances in young children with ASD. In a prior pilot study (R34MH082882 – PI Johnson97), we showed  
that our SPT for young children with ASD and sleep disturbances was acceptable to parents and reliably 
delivered by therapists (see Support section for  reference of the published paper of this pilot trial). We now 
propose a RCT to test the efficacy of telehealth delivered SPT against parent education – which will control for 
time and attention.  
 
Telehealth and ASD 
Telehealth, also referred to as telemedicine and more recently telepractice, is the use of communication 
technologies to allow delivery of services across a range of conditions and over geographical distances.158  The 
capacity of telehealth to deliver empirically based interventions for children with ASD holds promise as a 
means to close the gap between demand for services and the availability of autism specialist in underserved and 
rural areas such as those making up large swaths of the state of Florida.  Despite the potential for telehealth in 
the delivery of assessment and treatment of children with ASD, this has received limited research attention.  A 
few studies have demonstrated the use of telehealth to delivery interventions that are acceptable to parents but 
this is a under developed area at present.159-163  Treatment for sleep is particularly suited for telehealth as this 
allows for more ecologically sound delivery of the intervention close to bedtime.   
 

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Preliminary Data 
  
Do previous findings suggest SPT for sleep disturbances in children ASD can be effective?  
 In our prior NIH-funded pilot study (R34MH082882; Johnson, Turner, Foldes, Brooks, Kronk, Wiggs 97),  we 
showed  that our structured 5 session parent training intervention for young children with ASD and sleep 
disturbances was acceptable to parents and reliably delivered by therapists in a clinic setting.  Parents attended 
97% of expected sessions; parent satisfaction was high. Treatment fidelity (therapist integrity and parent 
adherence) was over 95%.  The SPT group 
improved significantly more than the 
comparison group based on the primary 
outcome of the CSI of the MSPSQ (see 
Figure 2).97  Using a benchmark of >30% 
improvement on the CSI, the SPT group had a 
positive response rate of 60% compared to the 
PE group (33%).  Again, this study was 
delivered in a tertiary, specialized setting 
requiring parents to make many trips to an 
urban area; some families traveled over two 
hours to participate.   
 
 
 
 
What was learned from our previous study?  
A number of lessons were learned from this earlier study which will benefit this current project.  First, 
telehealth SPT will be delivered over 10 weeks (versus 8 weeks in the previous study). This provides more time 
for parental application of strategies in the home and more time to detect change.  Second, the time and distance 
was a barrier for potential participants who would have otherwise met eligibility criteria. 
What is the impact of child sleep disturbance on parents?  
 In 49 children (mean = 3.48+ 1.02 years) with ASD and their parents, the CSI was highly correlated with a 
measure of parent sleep quality (Pittsburgh Sleep Quality Index) (r=.52; p <.001).  As sleep disturbances in 
children increased, parents’ sleep worsened.164   
 
Experience with the use of telehealth platforms?   
Dr. Johnson and colleagues are currently conducting an NIH-funded multi-site pilot study of a behaviorally-
based parent training program targeting feeding problems in young children with ASD. The study utilizes a 
HIPAA-compliant teleconferencing system (VSEE) to provide clinic-to-home parent-child coaching during 
mealtimes even though the parent training sessions per se are provided in a clinic setting.  All families 
randomized to treatment thus far (N=22) have been able to successfully connect through the system in order to 
receive in-vivo coaching from a therapist during mealtimes.  In conducting this trial, the idea to use a telehealth 
platform in the delivery of SPT was generated. The use of a telehealth platform has particular advantages to 
address sleep disturbances.  Aside from the advantage of reaching families who may be a distance from a 
university setting, the use of  the platform allows more flexibility in scheduling to include scheduling in the 
evening around bedtime, allows for real-time parent-child coaching soon after learning about the procedures 
discussed, and overall greatly enhances the ecological validity of the intervention. 
 

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For this trial, the telehealth platform will be the Cleveland Clinic Express Care Online. This platform is also 
HIPAA-compliant, and has capabilities that are similar to VSEE.  
 
 
Across a range from mild to severe, as many as 80% of children with autism spectrum disorder (ASD) have 
sleep disturbances.9,12,94,97,165 Sleep problems in typically developing children have adverse impacts on daytime 
behavior, emotion regulation, learning, physical health, as well as parent and family functioning.52,84,123,166,167 
For children with ASD whose development is compromised by a range of deficits, the impact of sleep 
disturbances may be more far reaching.  Given the improved recognition of ASD and the prevalence of sleep 
disturbances in this pediatric population, increased demand for treatment of children with ASD and sleep 
disturbances in pediatric sleep clinics, community behavioral health clinics and specialized ASD programs is 
inevitable. Accumulating data indicate that behaviorally based interventions for sleep disturbance can be 
effective. Despite the recommendation for these interventions in pediatrics broadly168 and ASD specifically, 
there have been few randomized controlled trials of behavioral interventions for sleep disturbance in children 
with ASD and none of these small trials included telehealth. 
     In response to FY17 ARP Clinical Trial Award funding opportunity (W81XWH-17-ARP-CTA), this 
four-year study will test the efficacy of a behavioral parent training intervention specifically designed for sleep 
disturbances and delivered individually through the HIPAA compliant Cleveland Clinic Express Care Online 
telehealth platform. This study will address the following areas of interest:  1) Behavioral, cognitive and 
other non-pharmacological therapies and 2) Therapies to alleviate conditions co-occurring in ASD (e.g, 
sleep disturbances).  
      A sample of 90 children with ASD (ages 2 to less than 7 years) and moderate or greater sleep disturbances 
will be randomly assigned to 10 weeks of a structured, 5 session sleep parent training (SPT) program or 10 
weeks of a structured, 5 session parent education (SPE) program. Our recently completed randomized pilot trial 
(n=33) demonstrated that SPT is acceptable to parents and provided promising preliminary efficacy data.97   We 
now propose an efficacy study of SPT delivered individually via telehealth platform for sleep disturbances in 
young children with ASD.  We will also examine the impact of SPT on the child’s overall functioning and 
parental quality of life.  Children who do not show a positive response to SPE will be offered SPT at no charge 
by study therapists.  
 
Primary Aim 
To evaluate the efficacy of telehealth deliver of SPT (n=45) compared to telehealth delivery of SPE (n=45) for 
sleep disturbance in children with ASD.   
Hypothesis 1:  After 10 weeks of treatment, children whose parents receive SPT will show greater improvement 
in sleep as evidenced by reduction on the Composite Sleep Index (CSI) of the modified Simonds and Parraga 
Sleep Questionnaire97,144 compared to children whose parents receive SPE.    
Hypothesis 2:  After 10 weeks of treatment, children whose parents receive SPT will show a significantly higher 
rate of overall improvement on the Improvement scale of the Clinical Global Impression (CGI-I), as assessed by 
an independent evaluator masked to group assignment, compared to children whose parents receive SPE. 
Ratings of Much Improved or Very Much Improved will be used to define positive response.   
Hypothesis 3:  After 10 weeks of treatment, children whose parents receive SPT will show significantly reduced 
disruptive behavior on the parent-rated Irritability subscale of the Aberrant Behavior Checklist (ABC) 
compared to children whose parents receive SPE. 
Hypothesis 4: At post-treatment follow up on Week 16, children in the SPT group will continue to show 
significantly lower scores on the CSI and a significantly higher rate of positive response on the CGI-I scored by 
an Independent Evaluator masked to treatment assignment compared to children in SPE.   
Secondary Aim 
To evaluate the impact of SPT on parental quality of life (parental stress, parental competency, mental health 
and sleep quality) compared to SPE.  
Objectives / Specific Aims / Hypotheses 

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Hypothesis 1:  After 10 weeks of treatment, parents enrolled in SPT will report lower levels of stress and higher 
levels of competency and health as measured by the Parenting Stress Index (PSI), Parenting Sense of 
Competence (PSOC), and Parent Health Questionnaire (PHQ) compared to parents in SPE.  
Hypothesis 2:  After 10 weeks of treatment, parents receiving SPT will report improved sleep for themselves on 
the Pittsburgh Sleep Quality Index (PSQI) compared to parents receiving SPE.  
 
 
 As shown in Figure 2, 90 eligible subjects will be randomly assigned in a 1:1 ratio to sleep parent training 
(SPT) or sleep parent education (SPE) using a randomized block design (random blocks of sizes 4 and 8), with 
allocation concealed to investigators.  Both treatments provide 5 individually-delivered sessions over 10 weeks. 
All participants will be assessed on study outcomes at Weeks 5 and 10 as well as 6 weeks post-treatment.  
Parents who complete SPE may receive SPT after the Week 16 evaluation.  
 
Inclusion/Exclusion Criteria 
Inclusion Criteria 
1.  Both genders >2 and <7 years of age [RATIONALE:  Based on pilot findings with similar age range97] 
2.  Clinical diagnosis of ASD corroborated by the Modified Checklist for Autism in Toddlers169 or the Social 
Communication Questionnaire.170  We will collect the MCHAT on children 2-3 years of age, both MCHAT and 
SCQ on children >3-<6, and SCQ for children >6-7 years of age via REDCap (Research Electronic Data 
Capture,171 see details in the Data Management section). We will use recommended cutoff scores (score of 8 for 
MCHAT and 15 for SCQ) for inclusion.   
3.  Score of >5 on the CSI and a Clinical Global Impression Severity (CGI-S) score of Moderate or greater. 
[RATIONALE:  This CSI score reflects moderate sleep disturbances and was the entry score in prior studies by 
Johnson et al97 and Wiggs and 
Stores;144 The CGI-S score of 
Moderate is commonly used as 
clinician validation of parent ratings.]      
4.  Medication and supplement free or 
on stable medication or supplements 
(no changes in the past 6 weeks and no 
planned changes for 16 weeks). 
[RATIONALE:  Many children with 
ASD are on medication for various 
target behaviors that may affect sleep. 
Children on stable medication (or 
supplement) for sleep, who otherwise 
meet study entry criteria, will be 
included because residual sleep 
problems remain. Including children 
on stable medication (or supplement) 
will enhance the representativeness of 
the study sample.]   
5. Parental proficiency in spoken and 
written English language. [RATIONALE:  At the present time, study materials and many of the study measures 
are available only in English.  If SPT is efficacious, we will take the next steps to translate the manual]. 
Exclusion Criteria 
1.  Children with a serious medical condition or a known or suspected medical cause for sleep disturbances 
(e.g., nocturnal seizures, unresolved gastrointestinal problems such as reflux or constipation). 
2.  Children with a psychiatric disorder or serious behavioral problems requiring immediate treatment. 
Study Design 

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3.  Children with known or suspected sleep apnea, restless legs, or periodic limb movements during sleep, or a 
circadian-based sleep disorder (e.g. delayed or advanced sleep phase syndrome) based on history and all 
available information.  [RATIONALE:  Children with these conditions warrant a different treatment.  We will 
provide referrals as needed.]  
 
Recruitment  
To randomize 90 subjects, we expect to screen approximately 120 subjects.  Approved advertisements about 
the project will be circulated within the Cleveland Clinic Center for Autism and other key programs within the 
Cleveland Clinic systems.  Regional autism programs in the community will also be approached and provided 
information about the study.  In the state of Florida, the university-based Centers for Autism and Related 
Disabilities (CARDS), with whom the PI has relationships, have over 3000 children registered in this young 
age range.  The study will also be posted on ClinicalTrials.com.  With distance not a limiting factor with 
telehealth delivery, recruitment is anticipated to be easily attainable. 
 
Study Procedures and Randomization 
Visit Schedule for Assessments   
Screening Visit:  
Subjects who appear to be eligible on a telephone interview will be scheduled for an Express Care Online 
screening visit. After obtaining informed consent which the family will access and sign using a REDCap link, 
parents will completed the assessment measures to confirm eligibility (see Table 1).  
Baseline Visit:   
Once eligibility is confirmed, an Express Care Online baseline visit will occur within 7-14 days of screening to 
complete additional measures (see Table 1). Parents will also be instructed to take photographs of their child’s 
sleep environment for review and treatment planning during the baseline visit.   
Randomization:  
 Participants will be randomly assigned to SPT or SPE at the conclusion of the baseline visit in a 1:1 ratio.  A 
randomized block design (with random blocks of size 4 and 8) will be used to ensure balance as well as 
maintaining the blinding of allocation assignment by investigators.  The randomization module in REDCap will 
be utilized to reveal the assignment for each participant.  Assignment status will be maintained in a separate 
REDCap data set, with a shared identifier to be able to link to the study database for final analysis.  Limited 
study staff who are not masked to treatment group assignment will have access to this database. 
Post-randomization Assessments:   
Assessments for both groups will be repeated at Weeks 5, 10 and 16 (see Table 1). The classification of positive 
or negative response will be made at Week 10 (endpoint of the randomized trial). To protect the treatment blind 
for IEs and to assess the effects of time within each treatment, all subjects will be asked to return at Week 16. 
 
Establishing Study Inclusion Criteria, & Subject Characterization  
Developmental, Medical, & Sleep History.   
This questionnaire will be completed by the parent / caregiver at screening to document prenatal, perinatal or 
postnatal medical and developmental histories including, sleep, medication and past assessments (see Survey 
and Questionnaires section). If any questions arise that would exclude the child and/or warrant other care, we 
will discuss with the family.  This history form requires 20-30 minutes to complete. 
The Modified Checklist for Autism in Toddlers (M-CHAT-R)169 is a 20 items screening measure to detect high 
risk toddlers for ASD.  This measure has been well validated and widely used. Scores between 8-20 are in the 
high risk range. We will use a score of >8 to corroborate the clinical diagnosis required for CARD registration. 
Internal consistency across all of the M-CHAT-R items fell below the adequate threshold (Cronbach’s alpha = 
0.63); however, when the second stage of the M-CHAT-R was examined internal consistency was found to be 
adequate (Cronbach’s alpha = 0.79). The M-CHAT-R initial scoring, with a cutoff score of 3, has a sensitivity 
of 0.911, and specificity of 0.955, both with a 95% CI. 169 M-CHAT requires 10-15 minutes to complete and is 
written on 4th grade reading level. 
The Social Communication Questionnaire (SCQ)170 is a parent report screening measure for autism spectrum 

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disorders (ASD) based on the Autism Diagnostic Interview-Revised (ADI-R) algorithm items. It has 40 yes and 
no questions centered around core features of ASD, and can be complete in 10-15 minutes. The SCQ shows 
high discriminative validity between ASD and non ASD populations, similar to the much lengthier ADI-R. 
ROC analyses established a cutoff score of 15 on the SCQ to differentiate between ASDs and other diagnoses. 
At this cutoff score, sensitivity was .85 and specificity was .75. The alpha index of internal consistency was 
uniform across diagnostic groups, ranging from .84 to .93.  A cut off score of >15 will be used to corroborate a 
clinical diagnosis and used for inclusion.  The SCQ requires 10 minutes to complete and written on 4th grade 
reading level. 
Clinical Global Impression-Severity (CGI-S)172  
This 7-point scale ranges from 1 (Normal) through 4 (Moderate) to 7 (Extreme).  Although sleep problems will 
be given particular weight, independent evaluators will consider all aspects of the child’s condition to assign the 
CGI-S score. A score of > 4 (Moderate) is required for entry.  
 
 
Outcome Measures  
Sleep Measure 
 Composite Sleep Index (CSI) from the MSPSQ97,144,173  
The CSI is a 6-item parent-report measure where items are rated 0 to 2 (range 0 to 12) with higher scores 
reflecting greater sleep problems. Thus, change in an item score of 1 or 2 points reflects a clinically relevant 
change.  For example, for the question on frequency of night wakings, a reduction from 2 to 1 point would 
reflect improvement in night wakings from every night to one-two nights per week; a reduction to 0 would 
reflect an improvement to once a month or less. The reliability and validity of the CSI has been established as a 
nested scale within the MSPSQ.174 Thus, we will use the full MSPSQ. Wiggs and Stores175 reported the test-
retest reliabilities for a 2 week period to be .83 to 1.0. In a larger study of 345 individuals with intellectual 
disability, Maas et al176 found the internal consistency of the items of the MSPSQ to be good (Cronbach’s α = 
.80). Maas et al176 also evaluated the convergent validity of the MSPSQ with a similar measure, the Sleep 
Disturbance Scale for Children (SDSC) and found a correlation (r = .79, p<.001) showing adequate validity. 
The MSPSQ has been reported to be acceptable to parents.175 This measure can be completed within 5-10 

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minutes and is at a 5th grade reading level. 
 
Child Behavior Measures 
Improvement scale of the Clinical Global Impression (CGI-I)172 
This is a clinician-rated, 7-point scale designed to measure overall improvement from baseline. Scores range 
from 1 (Very Much Improved) to 4 (Unchanged) to 7 (Very Much Worse). An independent evaluator (IE) 
blinded to group assignment will use all available information to judge treatment response. By convention, 
CGI-I ratings of Much Improved (score of 2) or Very Much Improved (score of 1) are used to classify subjects 
as positive responders. All other scores classify subjects as negative responders. An essential contributor to the 
CGI-I is the content of the semi-structured Parent Target Problem interview.31 At baseline, the IE asks the 
parent to nominate the child’s two most important problems. Based on the study entry criteria, we expect that 
one problem will be sleep related. The parent will also be asked to identify a second problem. Through brief 
discussion, the frequency (for episodic behaviors such as night wakings) or constancy (hyperactivity) reflecting 
more enduring patterns, intensity and impact of the behavior on the family are established. Responses from this 
systematic inquiry are documented in a brief narrative. The narrative will be reviewed and revised at Weeks 5, 
10 and 16. This method has been shown to be reliable and valid in a previous parent training study31,177 and 
currently being used in our RCT on parent training for feeding problems.   
Aberrant Behavior Checklist.178,179  
This is a reliable and valid 58-item parent-report questionnaire with five subscales:  Irritability (agitation, 
aggression and self-injurious behaviors), Social Withdrawal, Stereotyped Behaviors, Hyperactivity, and 
Inappropriate Speech. The ABC has shown adequate sensitivity to change in several pharmacological and 
behavioral treatment studies.148,180-183   The revised ABC manual184 cites 35 scientific papers that support the 
convergent validity of the ABC, and its concurrent validity with several established instruments regularly used 
in intellectually and developmentally disabled populations. Each item is rated on a Likert scale from 0 (not a 
problem) to 3 (severe in degree).  For the current study, we are primarily interested in change of the Irritability 
and Hyperactivity subscales as a proxy for sleep-related impairment (i.e., daytime behaviors secondary to sleep 
disturbances).  Requiring an 8th grade reading level, this measure requires 15-20 minutes to complete. 
 
Quality of Life Measures 
Parenting Stress Index-Short Form (PSI)185  
This is a 36-item parent-completed questionnaire for children 12 years of age and younger and has three scales: 
1) Parental Distress; 2) Difficult Child Characteristics; and, 3) Dysfunctional Parent-Child Interaction. This 
measure was developed from the Parenting Stress Index Full Form using factor analysis, and has been used to 
assess parental stress and parent-child relationships in children with autism and intellectual disabilities.185-
189  The PSI has good test-retest reliability with an average score of .76 (min= .68, max= .85), and internal 
consistency (Cronbach's alpha average of .85, min= .8, max=.91). A total score of 88 (85th percentile) and above 
is considered in the clinically significant range for parental stress. The PSI has good convergent and concurrent 
validity across clinical and nonclinical samples, and diverse populations.  We confirmed the factor structure in a 
recent study.190  We have used this for several other trials and it has been shown to be sensitive to change in 
parent training studies.191  This measure may be completed within 10-20 minutes and written at a 3rd grade 
reading level.  
Parent Health Questionnaire-4 (PHQ-4)192  
This brief self-report is designed to assess parental mental health. It has been shown to be an effective screen for 
anxiety and depression disorders. Requiring 5 minutes to completed and written at 5th grade reading level. 
The Parenting Sense of Competence scale (PSOC)193  
This 17-item scale was developed to assess parental self-efficacy. Each item is answered on a 6-point scale 
ranging from strongly disagree to strongly agree. The measure has high internal consistency and solid test-
retest reliability. The Satisfaction subscale measures parental motivation and frustration (e.g., “Even though 
being a parent could be rewarding, I am frustrated now while my child is at his/her present age”). The Efficacy 
subscale measures perceived self-efficacy to change the child’s behavior (e.g., “I meet my own personal 
expectations for expertise in caring for my child”). The PSOC also yields a Total Competence score, with 

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higher scores reflecting higher competence. In a community sample of mothers,194 subscale total scores of 
Satisfaction (22.72) and Efficacy (22.03) were reported. We have used this measure in another study of parent 
training and it has been shown to be sensitive to change.195 This measure is written at an 8th grade reading level 
and requires approximately 15 minutes to complete. 
Pittsburgh Sleep Quality Index (PSQI)196  
This 19-item, self-rated questionnaire will be completed by parents. It is used in adult sleep medicine research 
as a reliable measure of sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, 
use of sleep medication, and daytime functioning. Overall, it has a reliability coefficient (Cronbach’s alpha) of 
0.83, indicating a high degree of internal consistency. For the subgroup that was tested at two time points, the 
correlation coefficient for global PSQI scores was 0.85 (p<0.001). Distribution of global PSQI scores differed 
between groups. A cutoff score of 5 correctly identified 88.5% of all patients and controls (kappa=0.75, 
p<0.001). This represents a sensitivity of 89.6% and a specificity of 86.5%. PSQI estimates of sleep variables 
were compared to polysomnographic findings. T-tests showed no differences between PSQI sleep latency 
estimates and those found using polysomnography, but estimates of usual sleep duration and efficiency were 
greater than those obtained through polysomnography. The reading level for this widely used measure is  
written at  the 3rd-4th grade reading level and requires around 10 minutes.   
 
Clinician Measures  
Treatment Fidelity Checklist  
These checklists include the therapist integrity goals, parent objectives and level of adherence for each SPT and 
SPE session.  Therapists rate themselves on 5-7 session-specific goals on a scale of 0 to 2 as follows:  (0 = Goal 
was not achieved; 1 = Goal was partially achieved; 2 = Goal was fully achieved).  Therapists are asked to 
comment on items rated 0.  Parent objectives and adherence are scored on a similar scale. The score for each 
session = sum of scores for all items in that session divided by the total possible score X 100. An example of a 
treatment fidelity checklist is in Intervention section.   These treatment fidelity checklists have been modeled 
after four other previously NIH-funded projects.31,97,148,191 
Safety/Adverse Event Review Form  
Starting at the screen visit, the masked Independent Evaluator (IE) will ask about recent health complaints, use 
of medical services and concomitant medications. The Safety/Adverse Event Review Form also asks about the 
child’s sleep, appetite and bowel habits. Screen data will be documented so that new adverse events can be 
elicited and recorded using the same Safety/Adverse Event Review Form. Reports of new adverse events or 
worsening of previously reported events will be rated mild (present, but not a problem), moderate (present, 
posing a problem or intervention required to prevent a problem) or severe (present, posing a problem and 
needed intervention). Hospitalization will be documented as a serious adverse event.  A “yes” answer to any of 
these queries will prompt further questions to determine duration and severity.  The onset, offset and severity of 
adverse events will be documented whether presumed to be related to the study treatment or not (see Human 
Subjects section).  
 
Description of Interventions 
Behavioral Parent Training for Sleep Disturbances (SPT)  
SPT is an expanded version of the single sleep session that the PI (C. Johnson) developed for the RUPP Autism 
Network Parent Training (PT) program (U10MH66764] and the recently completed Research Units on 
Behavioral Intervention PT program [RUBI, R01MH1081148MH; Johnson, PI).31,197,198 SPT was developed 
and evaluated for feasibility and initial test of efficacy (R34MH08288: Johnson, PI).97 The five SPT sessions 
(each 60-90 minutes in duration) are individually delivered over 10-weeks (see Table 2). In addition to the five 
sessions, there are three home visits conducted via  Express Care Online (HIPAA compliant video-chat).  After 
Session A, session order may be adjusted to address child-specific problems. For example, if night wakings is 
the highest priority, Session C may be offered before Session B to introduce the use of extinction or scheduled 
wakings. Spreading the sessions over 10 weeks allows for scheduling flexibility and opportunities to present 
child-specific optional materials (outlined in Table 2). All parents/caregivers who are involved with the child’s 
bedtime and sleep will be encouraged to participate.  Hopefully, telehealth delivery will facilitate fuller 

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inclusion of caregivers.  Each session employs direct instruction, modeling, and role-playing to promote 
parental skill acquisition. The SPT manual includes a therapist script and parent activity sheets for each session. 
Video vignettes have been developed for each session that model specific techniques and show a parent 
incorrectly applying the technique for different bedtime problems. For example, vignettes show a parent 
reacting to a child’s tantrum at bedtime and a parent responding to a child calling out in the middle of the night. 
By showing ineffective parent management strategies, the video vignettes supplement direct instruction. In 
discussion, the parent is encouraged to identify the error in the vignette and to consider alternative responses. 
Thus, the video vignettes serve as a check on the parents’ acquisition of concepts and techniques and permit the 
therapist to clarify uncertainties. Parents are given homework assignments to practice new skills learned in each 
session along with data collection assignments. The materials from one of the SPT session are provided in the 
Intervention section.  
 
Rationale for SPT 
Parent training based on the principles of applied behavior analysis is an empirically supported intervention for 

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young children with ASD and disruptive behavior.31  For sleep problems, parent training was also chosen for 
pragmatic reasons: a parent/caregiver is available at bedtime when sleep disturbances occur; and parents (and 
other family members) may be adversely affected by the child’s sleep disturbance. The decision to have all 
participants complete the five-session SPT program, regardless of primary sleep complaint is based on the 
observation that children with ASD often have more than one sleep problem and sleep problems can change 
over time in this population.97 Thus, SPT provides a comprehensive intervention that teaches parents the basic 
concepts and practical skills to address an array of sleep problems. One-on-one delivery of SPT permits 
flexibility for child-specific problems within the program. 
 
Rationale and Modifications of SPT for Telehealth Delivery.   
Telehealth delivery of SPT is expected to not only be more feasible in that it will allow families who live a 
distance from tertiary, specialized autism centers to participate, but is more optimal in that materials from the 
sessions may be delivered at a time more convenient for them; even soon before bedtime so content is fresh for 
parents.  This will also allow us to complete more parent-child coaching in this manner of delivery.  Overall, 
ecological validity of the intervention will be enhanced by delivering SPT via telehealth platform.  
Modifications to be made to allow for telehealth delivery are minimal.  Session activity sheets the parents will 
need will be pushed out by REDCap ahead of time.  Hard copies will also be mailed if families prefer.  The 
video vignettes used in each session will be viewed via the split screen of Express Care Online.  We can also 
provide the families with a DVD of the videos if they wish.  Materials that might have been developed in 
session for the family to use at home (for example, a visual schedule) will be overnight mailed to the family as 
well as pushed out to them by REDCap link.   
 
Sleep Parent Education (SPE) 
SPE consists of five 60-90 minute sessions, delivered individually over 10 weeks.  As with SPT, we expect one 
parent to attend all sessions, but another parent or caregiver is invited to attend SPE. As shown in Table 3, SPE 
provides useful information to families of young children with ASD and sleep problems.  Session A is designed 
to develop rapport. The sleep hygiene session (Session B) has been modeled from the RUBI manual. The other 

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sessions include a systematic presentation on several relevant topics (see Table 3).  An example of a SPE 
session is provided in the Intervention section.  This control condition is intended to parallel what would be 
offered in typical care, but by telehealth, where a parent might be educated about ASD as well as attend an 
outpatient appointment at a sleep clinic. 
Rationale for SPE as the control condition 
SPE is a structured program intended to mimic competent treatment as usual.  Thus, SPE is an accepted 
treatment and serves as an active comparator that controls for time and attention. We have conducted two 
previous randomized trials using parent education as the control condition. In both studies, attrition was low and 
satisfaction was high.31,97  
Rationale and Modifications of SPE for Telehealth Delivery.  Given our success with using SPE as an active 
comparator in previous studies, we are optimistic about using this control for the current study.  As with SPT, 
minimal modifications will need to be made to deliver SPE individually via telehealth platform.  All materials 
parents will need for SPE will be pushed out via REDCap, with the option of a hard copy mailed to them as 
well.  In fact, telehealth delivery of SPE is more interactive than many internet-based programs that parents use 
to seek knowledge about ASD (e.g. Autism Speaks, Autism Navigator, Organization for Autism Research).  
Parents in SPE will receive the benefits of a therapist to respond to their specific questions and as 
aforementioned, parents in previous trials have been extremely satisfied with SPE.31,97  
 
Quality Control 
Assessments 
Measures to be used for this study have all been used in prior studies by Dr. Johnson.  At a start up meeting, the 
research team will review all measures.  Dr. Johnson will review with independent evaluators (IEs) on the 
elicitation and documentation of the Parent Target Problems specifically around and to use all available 
information to rate the CGI-S and CGI-I, and to conduct the Safety/Adverse Event Review. 
Therapist Selection, Training & Fidelity Monitoring 
Doctoral or masters level practitioners with behavioral intervention experience in children with ASD will 
provide study treatments. Dr. Johnson, who has extensive therapist training experience, will train study 
therapist(s). Therapists will read through the treatment manual and observe sessions (or videos) by an 
experienced clinician delivering SPT and SPE.   Similar to our other studies, therapists will be trained to 80% 
reliability for each session of both manuals with a non-study subject prior to treating randomized study subjects. 
The reliability will be confirmed by review of audio recordings by Dr. Johnson.  After each SPT or SPE session, 
therapists will rate their own fidelity on a set of session-specific goals using a 0-2 scale (0=item not covered, 
1=partially covered, 2=fully covered). All sessions in the randomized trial will be audio recorded and a 10% 
sample of randomly selected recordings will be scored to monitor therapist fidelity throughout the study. If 
therapist fidelity falls below criterion, a remedial plan will be implemented. Another element of treatment 
integrity is parental adherence (compliance and engagement). Therapists will rate parental adherence to SPT or 
SPE on a similar 0 to 2 scale. Parental adherence that falls below 70% in two successive sessions will be 
directly discussed with the parent.  A session treatment fidelity form example may be found in the Intervention 
section along with session materials.   
 
Data Management and Analyses 
Data Management 
Data will be collected directly via the web-based data entry site, developed through REDCap.171  REDCap is a 
secure, web-based application for building and managing online surveys and databases. The REDCap software, 
training videos and basic end-user support are provided to all Cleveland Clinic investigators without charge. 
The system is managed by the Cleveland Clinic Center for Clinical Research and Learner Research Institute 
Research Computing Services.  REDCap resides on servers within the Learner Research Institute. This 
centrally-located data center features redundant, high availability infrastructure components, including over 
100TB of XIOTech SAN and SATA storage capacity, IBM Tivoli tape libraries for backup, HP servers, 
VMWare Virtual Infrastructure Clusters and a system-wide Liebert 130KVA Uninterrupted Power Supply. Data 
are backed up hourly at 3 separate, secure locations.  

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    Data management analyst (TBN) under the direction of biostatistician (Sarah Worley) will develop the online 
data collection forms through REDCap. The data entry forms will be designed with as few open-ended text 
fields, and as many user-friendly drop-down answer boxes or check boxes as possible, with little opportunity for 
responses to be provided with implausible values.  Clinic data will be entered by the study coordinators; the 
entry forms will be developed with built-in range checks and automatically-calculated fields to reduce the 
possibilities of data entry errors.  Branching logic will be extensively used so questions/fields do not need to 
appear when they are illogical. The database will be pilot-tested after development, with feedback from the 
coordinator on ease of use.  A separate randomization assignment data set will exist with a common identifier to 
allow for linkage with the study database for final analyses. This randomization data set will be maintained on a 
secure server and only accessible by the data management team. During enrollment, the data manager will 
regularly check for data inconsistencies, omissions, and errors, confirming with the coordinator when outliers 
and unusual values are observed.  The data manager will randomly select 10% of data on a quarterly basis to be 
checked for data entry quality; discrepancies will trigger review of data collection and entry procedures as 
appropriate.  The data management team will attend all study meetings to ensure constant communication about 
data issues that may arise throughout the study. 
 
Sample Size and Power Calculation for Primary Hypotheses. 
We base our power analysis on the primary aim/analysis comparing efficacy of SPT for sleep disturbance in 
children with ASD compared to SPE, with the CSI score as the primary outcome.  Specifically, we aim to 
achieve 90% power to detect a meaningful difference in change in CSI scores between baseline and 10 weeks 
between the SPT and SPE groups (α = 0.05). We assume we will have roughly 40 participants per group (80 
total) after allowing for an attrition rate of about 10% in each group as has been average from our previous 
clinical trials.  A 2-point difference in the CSI score (CSI description below) is clinically relevant.  Based on 
our preliminary study (Figure 1), we observed a SD = 2.5 for the difference between baseline and 8-week CSI 
scores in the treatment group and a SD = 2.3 for the difference in the control group.  The SD’s for the 4-week 
difference were also equal to 2.3 in both groups; thus a conservative SD estimate of 2.5 for the difference 
between baseline and 10 weeks was used.  For the parameters listed above and a total final sample size of 80, 
we will have 90% power to detect a difference in 10-week CSI change of 1.7 points or greater.  Given the 
constant SD’s observed over time, this power analysis is reasonable for 5-week comparisons as well.  For 
hypothesis 2, specifically focusing on the CGI-I, we predict somewhere between 25%-40% positive response in 
the SPE group. With 45 per group (CGI-I drop-outs will be classified as negative responders by default), we 
will have 90% power (α=0.05) to detect a 32% or greater difference in positive response rate (57%-72%, 
respectively).    
  
Statistical Analysis 
Statistical analyses will be conducted by Sarah Worley in collaboration with the study team. We will begin with 
descriptive statistics for baseline data across treatment groups. Study coordinator and data manager will inspect 
data for errors, inconsistencies, and incomplete information across time points (as a follow-up to the regular 
data management procedures that will occur throughout the study, described above). This will include 
examination of frequency tables and scatter plots. Data anomalies and outliers will be examined and corrected if 
necessary.  These preliminary analyses will include descriptive statistics in each treatment group for all outcome 
variables, plots of longitudinal data over time, and examination of distributions within groups at important 
nodal points (e.g., Baseline, Week 5, 10 and 16).  For the primary analysis, we will use a linear mixed model, 
which will make use of the repeated measurement of the CSI. Specifically, we will model change in CSI 
relative to baseline at weeks 5 and 10 (and week 16), with primary fixed effects of baseline CSI, treatment (SPT 
or SPE), time, and the interaction between time and treatment. No systematic trend with time will be initially 
assumed to allow for potential nonlinear trends; if linear changes are observed (and confirmed via statistical 
testing), we will model time as a continuous variable. With at most three repeated measurements, model 
selection of the covariance structure is minimized; we will model directly the variance of the outcome at each 
time point as well as the correlation between the three visits (i.e., unstructured covariance). We will examine 
whether the covariance needs to be modeled separately between the two treatment groups, as well as whether 

Version 1.2: 7-12-2018                                                                                                                                  Page 16 of 27 
we can use a more parsimonious covariance model to maximize statistical power.  Common model selection 
criteria will be used for this examination.199 Appropriate assumptions and model conditions will be verified 
prior to analysis. Tabled data will be presented as differences in means across time with 95% confidence 
intervals.  The Kenward-Roger approximation for the denominator degrees of freedom will be utilized to ensure 
valid inference of the fixed effects.200   A similar approach will be used for the key continuous secondary 
outcome (Total Sleep Time on actigraph) and other secondary measures such as the ABC- Irritability subscale, 
PSI scales, Parental Competence measure, etc. The key secondary analysis will use the chi-square test to 
compare the rate of positive response on the CGI-I in SPT versus SPE. Chi-square tests will also be used to 
compare the rates of adverse events across treatment groups. 
     Efficacy analyses will follow the intention-to-treat convention (including all randomized subjects). For 
modeling and hypothesis testing, the proposed likelihood-based approach regards missing data as missing at 
random (MAR; i.e., missing data are independent of unobserved data). Although there is no proven method for 
verifying the MAR assumption, the likelihood-based solutions are robust to violations of ignorable missing data 
(i.e., situations where the MAR assumption is not met).201 Prior to analyses for efficacy, we will examine the 
degree of randomness in missing data by comparing the frequency, reasons, pattern and time to dropout and 
missing values across treatment groups. If substantial differences in missingness occur across SPT and SPE  that 
cannot be adequately explained by observed variables, secondary sensitivity analyses employing the methods 
described by Carpenter and Kenward202 will be employed. These techniques will be considered cautiously in 
our analyses as they require certain assumptions that cannot be evaluated from the data under analysis. All 
analyses will be conducted using SAS v9.4 for Windows (Cary, NC, USA).  
     Given the planned sample size, we will not have sufficient statistical power to detect effect modifiers (i.e., 
compare the efficacy of the intervention among subgroups).  However, we do plan to examine and compare the 
efficacy of the intervention between subgroups via statistical interactions in the above models.  Variables of 
interest include age, IQ, and gender.  These estimates, if we observe possible differential effects, will serve as 
the basis for future, larger studies that target the comprehensive study by subgroups.   
 
The above general analysis plan holds for the majority of our aims/hypotheses.  We discuss specifics analysis 
considerations below for each aim/hypothesis as appropriate.   
 
Primary Aim 
To evaluate the efficacy of telehealth delivery of SPT for sleep disturbance in children with ASD compared to 
telehealth delivery of SPE.   
Hypothesis 1:  After 10 weeks of treatment, children whose parents receive SPT will show greater reduction on 
the CSI from the MSPSQ compared to those whose parents receive SPE.  Our modeling approach above 
describes how we will test this hypothesis, with change in CSI relative to baseline as our outcome to be modeled 
over the span of the study via linear mixed models (5 and 10 weeks).   
Hypothesis 2:  After 10 weeks of treatment, children in the SPT group will show significantly higher rates of 
positive response than children in the SPE group on the Improvement scale of the Clinical Global Impression 
(CGI-I) rated by an independent evaluator masked to group assignment. The proportion of positive response 
(Much Improved or Very Much Improved) in SPT vs SPE will be tested using a Chi Square test. 
Hypothesis 3:  After 10 weeks of treatment, children whose parents receive SPT will show significantly lower 
rates of disruptive behaviors on the parent-rated ABC-Irritability subscale compared to children whose parents 
receive SPE. To test this hypothesis, we will use the same linear mixed model approach described for the CSI. 
The other ABC subscales will be examined in exploratory analyses.  
Hypothesis 4: As noted above, all subjects will be asked to return at Week 16 to evaluate the post-treatment 
effects of SPT and SPE.  Parents will rate the CSI. The same treatment blinded IE will rate the CGI-I at post-
treatment follow up. We will essentially add the 16-week CSI measure to the modeling framework described 
above to further characterize CSI trends over a longer period of time, and to compare these trends between the 
two groups.  This modeling approach (in particular modeling the time point directly (i.e., not assuming a linear 
trend from baseline) will allow us to directly test for differences at 16 weeks. We will also compare the rate of 

Version 1.2: 7-12-2018                                                                                                                                  Page 17 of 27 
positive response on the CGI-I in the SPT versus SPE. Subjects who drop out before or after Week 10 will be 
classified as negative responders by default. \ 
 
Secondary Aim 
To evaluate the impact of SPT on parental quality of life (parental stress, sense of competence, mental health 
and sleep) compared to SPE.  
Hypothesis 1 and 2:  After 10 Weeks of treatment, parents in SPT will report lower levels of stress and higher 
levels of competency and overall health as measured by the PSI (stress), PSOC (competence), PHQ (mental 
health) and better PSQI (sleep) than parents in SPE. To test these hypotheses, we will use the same linear mixed 
model approach described for the CSI. Exploratory analyses will test whether parental quality of life shows 
greater change from baseline to week 16 on the PSI, PSOC, PSQ, and PSQI compared to SPE. 
Timetable of Projected Activities   
A total of 90 children will be 
recruited. In the second half 
of Year 01, each site will 
screen 17-18 subjects with 
the goal of randomizing 15 
subjects.  In Years 2 and 3, 
we aim intend to randomize 
30 subjects per year. In the 
first half of Year 04, we will 
screen 17-18 subjects to meet goal of randomizing the final 15 participants (see Table 4).   
 
 
 
 

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References 
 
1. 
Elsabbagh M, Divan G, Koh YJ, et al. Global prevalence of autism and other pervasive developmental 
disorders. Autism Research. 2012;5(3):160-179. 
2. 
Christensen DL, Baio J, Van Naarden Braun K, et al. Prevalence and characteristics of autism spectrum 
disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 
sites, United States, 2012. MMWR Surveillance Summaries. 2016;65(3):1-23. 
3. 
Brereton AV, Tonge BJ, Einfeld SL. Psychopathology in children and adolescents with autism 
compared to young people with intellectual disability. Journal of Autism and Developmental Disorders. 
2006;36(7):863-870. 
4. 
Hartley S, Sikora D, McCoy R. Prevalence and risk factors of maladaptive behaviour in young children 
with autistic disorder. Journal of Intellectual Disability Research. 2008;52(10):819-829. 
5. 
Lecavalier L. Behavioral and emotional problems in young people with pervasive developmental 
disorders: Relative prevalence, effects of subject characteristics, and empirical classification. Journal of 
Autism and Developmental Disorders. 2006;36(8):1101-1114. 
6. 
Rosenberg RE, Kaufmann WE, Law JK, Law PA. Parent report of community psychiatric comorbid 
diagnoses in autism spectrum disorders. Autism research and treatment. 2011;2011. 
7. 
Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in children 
with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a population-derived 
sample. Journal of the American Academy of Child & Adolescent Psychiatry. 2008;47(8):921-929. 
8. 
Hallett V, Lecavalier L, Sukhodolsky D, et al. Exploring the Manifestations of Anxiety in Children with 
Autism Spectrum Disorders. Journal of Autism and Developmental Disorders. 2013;43(10):2341-2352. 
9. 
Honomichl RD, Goodlin-Jones B, Burnham MM, Gaylor E, Anders T. Sleep patterns of children with 
pervasive developmental disorders. Journal of Autism and Developmental Disorders. 2002;32(6):553-
561. 
10. 
Johnson CR. Sleep problems in children with mental retardation and autism. Child and Adolescent 
Psychiatric Clinics of North America. 1996;5(3):673–683. 
11. 
Johnson CR, Turner KS, Foldes EL, Malow BA, Wiggs L. Comparison of sleep questionnaires in the 
assessment of sleep disturbances in children with autism spectrum disorders. Sleep Medicine. 
2012;13(7):795-801. 
12. 
Wiggs L, Stores G. Sleep patterns and sleep disorders in children with autistic spectrum disorders: 
insights using parent report and actigraphy. Developmental Medicine & Child Neurology. 
2004;46(6):372-380. 
13. 
Coury D. Medical treatment of autism spectrum disorders. Current opinion in neurology. 
2010;23(2):131-136. 
14. 
Knapp M, Mandell D, Buescher A, Cidav A. Autism: Economic impact and implications. Autism 
Summit, Investing in our Future. 2012. 
15. 
Rogers SJ, Vismara LA. Evidence-based comprehensive treatments for early autism. Journal of Clinical 
Child & Adolescent Psychology. 2008;37(1):8-38. 
16. 
Sallows GO, Graupner TD. Intensive behavioral treatment for children with autism: Four-year outcome 
and predictors. American Journal of Mental Retardation. 2005;110(6):417-438. 
17. 
Smith T, Scahill L, Dawson G, et al. Designing Research Studies on Psychosocial Interventions in 
Autism. Journal of Autism and Developmental Disorders. 2007;37(2):354-366. 
18. 
Prizant BM, Wetherby AM, Rubin E, Laurent AC, Rydell PJ. The SCERTS [TM] Model: A 
Comprehensive Educational Approach for Children with Autism Spectrum Disorders. ERIC; 2005. 

Version 1.2: 7-12-2018                                                                                                                                  Page 19 of 27 
19. 
Council NR. Educating children with autism. Committee on Educational Interventions for Children with 
Autism. . In: Lord C, McGee JP, eds. Division of Behavioral and Social Sciences and Education. 
Washington, DC:: National Academy Press; 2001. 
20. 
Matson JL, Dempsey T. Autism spectrum disorders: Pharmacotherapy for challenging behaviors. 
Journal of Developmental and Physical Disabilities. 2008;20(2):175-191. 
21. 
Scahill L, Martin A. Psychopharmacology. In: Volkmar F, Klin A, Paul R, eds. Handbook of Autism and 
Pervasive Developmental Disorders 3rd ed. New York: Wiley; 2005:1102-1117. 
22. 
Croen LA, Grether JK, Hoogstrate J, Selvin S. The changing prevalence of autism in California. Journal 
of Autism and Developmental Disorders. 2002;32:207-215. 
23. 
Gerhardt PF, Lainer I. Addressing the needs of adolescents and adults with autism: a crisis on the 
horizon. Journal of Contemporary Psychotherapy. 2011;41(1):37-45. 
24. 
Jensen VK, Sinclair LV. Treatment of autism in young children: behavioral intervention and applied 
behavior analysis. Infants & Young Children. 2002;14(4):42-52. 
25. 
Stahmer A. The Basic Structure of Community Early Intervention Programs for Children with Autism: 
Provider Descriptions. Journal of Autism and Developmental Disorders. 2007;37(7):1344-1354. 
26. 
Committee IAC. IACC strategic plan for autism spectrum disorder research. Washington (DC): US 
Department of Health and Human Services. 2011. 
27. 
Organization WH. Atlas: Global resources for persons with intellectual disabilities 2007. World Health 
Organization; 2007. 
28. 
Brookman-Frazee L, Drahota A, Stadnick N, Palinkas LA. Therapist perspectives on community mental 
health services for children with autism spectrum disorders. Administration and Policy in Mental Health 
and Mental Health Services Research. 2012;39(5):365-373. 
29. 
Meltzer LJ, Phillips C, Mindell JA. Clinical psychology training in sleep and sleep disorders. Journal of 
Clinical Psychology. 2009;65(3):305-318. 
30. 
Wacker DP, Lee JF, Dalmau YCP, et al. Conducting functional analyses of problem behavior via 
telehealth. Journal of Applied Behavior Analysis. 2013;46(1):31-46. 
31. 
Bearss K, Johnson, C.R., Smith, T. . Effect of parent training vs parent education on behavioral 
problems in children with autism spectrum disorder:  A randomized clinical trial. Journal of the 
American Medical Association. 2015;313(15):1524-1533. 
32. 
Garstang J, Wallis M. Randomized controlled trial of melatonin for children with autistic spectrum 
disorders and sleep problems. Child: Care, Health, and Development. 2006;32(5):585-589. 
33. 
Iglowstein I, Jenni OG, Molinari L, Largo RH. Sleep duration from infancy to adolescence: Reference 
values and generational trends. Pediatrics. 2003;111(2):302-307. 
34. 
Moore M, Allison D, Rosen CL. A review of pediatric nonrespiratory sleep disorders. Chest. 
2006;130(4):1252-1262. 
35. 
Meltzer LJ, Mindell JA. Sleep and sleep disorders in children and adolescents. Psychiatric Clinics of 
North America. 2006;29(4):1059-1076. 
36. 
Stores GE, Wiggs LE. Sleep disturbance in children and adolescents with disorders of development: Its 
significance and management. Cambridge University Press; 2001. 
37. 
Stores G. Sleep-wake function in children with neurodevelopmental and psychiatric disorders. Seminars 
in Pediatric Neurology. 2001;8(4):188-197. 
38. 
Dahl RE. The impact of inadequate sleep on children's daytime cognitive function. Seminars in 
Pediatric Neurology. 1996;3(1):44-50. 
39. 
Graven S. Sleep and brain development. Clinics in Perinatology. 2006;33(3):693. 
40. 
Kurth S, Ringli M, Geiger A, LeBourgeois MK, Jenni OG, Huber R. Mapping of Cortical Activity in the 
First Two Decades of Life: A High-Density Sleep Electroencephalogram Study. Journal of 
Neuroscience. 2010;30(40):13211-13219. 
41. 
Bernier A, Carlson SM, Bordeleau S, Carrier J. Relations between physiological and cognitive 
regulatory systems: Infant sleep regulation and subsequent executive functioning. Child Development. 
2010;81(6):1739-1752. 

Version 1.2: 7-12-2018                                                                                                                                  Page 20 of 27 
42. 
Frank MG, Issa NP, Stryker MP. Sleep enhances plasticity in the developing visual cortex. Neuron. 
2001;30(1):275. 
43. 
Goel N, Rao H, Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Semin 
Neurol. 2009;29(4):320-339. 
44. 
Maquet P. The Role of Sleep in Learning and Memory. Science. 2001;294(5544):1048-1052. 
45. 
Sadeh AVI, Gruber R, Raviv A. Sleep, neurobehavioral functioning, and behavior problems in school-
age children. Child Development. 2002;73(2):405-417. 
46. 
Stickgold R, Walker MP. Sleep and memory: the ongoing debate. Sleep. 2005;28(10):1225-1227. 
47. 
Walker MP, Stickgold R. Sleep, memory, and plasticity Annual review of psychology. 2006;57(1):139-
166. 
48. 
Leotta C, Carskadon M, Acebo C, Seifer R, Quinn B. Effects of acute sleep restriction on affective 
response in adolescents: Preliminary results. Sleep Research. 1997;26:201. 
49. 
Randazzo AC, Muehlbach MJ, Schweitzer PK, Walsh JK. Cognitive function following acute sleep 
restriction in children ages 10-14. Sleep: Journal of Sleep Research & Sleep Medicine. 1998. 
50. 
Steenari M-R, Vuontela V, Paavonen EJ, Carlson S, Fjällberg M, Aronen ET. Working memory and 
sleep in 6-to 13-year-old schoolchildren. Journal of the American Academy of Child & Adolescent 
Psychiatry. 2003;42(1):85-92. 
51. 
Vriend JL, Davidson FD, Corkum PV, Rusak B, McLaughlin EN, Chambers CT. Sleep quantity and 
quality in relation to daytime functioning in children. Children's Health Care. 2012;41(3):204-222. 
52. 
Sadeh A, Gruber R, Raviv A. The effects of sleep restritction and extension on school-age children: 
What a difference an hour makes. Child Development. 2003;74(2):444-455. 
53. 
Fallone G, Acebo C, Arnedt JT, Seifer R, Carskadon MA. Effects of acute sleep restriction on behavior, 
sustained attention, and response inhibition in children. Perceptual and Motor Skills 2001;93(1):213-
229. 
54. 
Fallone G, Acebo C, Seifer R, Carskadon MA. Experimental restriction of sleep opportunity in children: 
effects on teacher ratings. Sleep. 2005;28(12):1561. 
55. 
Gruber R, Grizenko N, Schwartz G, Bellingham J, Guzman R, Joober R. Performance on the continuous 
performance test in children with ADHD is associated with sleep efficiency. Sleep. 2007;30(8):1003. 
56. 
Gruber R, Xi T, Frenette S, Robert M, Vannasinh P, Carrier J. Sleep disturbances in prepubertal children 
with attention deficit hyperactivity disorder: a home polysomnography study. Sleep. 2009;32(3):343. 
57. 
Gruber R, Cassoff J, Frenette S, Wiebe S, Carrier J. Impact of sleep extension and restriction on 
children’s emotional lability and impulsivity. Pediatrics. 2012;130(5):e1155-e1161. 
58. 
Gruber R, Wiebe S, Montecalvo L, Brunetti B, Amsel R, Carrier J. Impact of sleep restriction on 
neurobehavioral functioning of children with attention deficit hyperactivity disorder. Sleep. 
2011;34(3):315. 
59. 
Peters JD, Biggs SN, Bauer KM, et al. The sensitivity of a PDA‐ based psychomotor vigilance task to 
sleep restriction in 10‐ year‐ old girls. Journal of Sleep Research. 2009;18(2):173-177. 
60. 
Fredriksen K, Rhodes J, Reddy R, Way N. Sleepless in Chicago: tracking the effects of adolescent sleep 
loss during the middle school years. Child Development. 2004;75(1):84-95. 
61. 
Gregory AM, Rijsdijk FV, Eley TC. A twin study of sleep difficulties in school aged children. Child 
Development. 2006;77(6):1668-1679. 
62. 
Kurnatowski P, Putyński L, Łapienis M, Kowalska B. Physical and emotional disturbances in children 
with adenotonsillar hypertrophy. The Journal of Laryngology & Otology. 2008;122(09):931-935. 
63. 
Carskadon MA, Harvey K, Dement WC. Sleep loss in young adolescents. Sleep. 1981;4(3):299-312. 
64. 
Wolfson AR, Carskadon MA. Sleep schedules and daytime functioning in adolescents. Child 
Development. 1998;69(4):875-887. 
65. 
Bates JE, Viken RJ, Alexander DB, Beyers J, Stockton L. Sleep and adjustment in preschool children: 
Sleep diary reports by mothers relate to behavior reports by teachers. Child Development. 
2002;73(1):62-75. 
66. 
Chu J, Richdale AL. Sleep quality and psychological wellbeing in mothers of children with 
developmental disabilities. Research in Developmental Disabilities. 2009;30(6):1512-1522. 

Version 1.2: 7-12-2018                                                                                                                                  Page 21 of 27 
67. 
Couturier JL, Speechley KN, Steele M, Norman R, Stringer B, Nicolson R. Parental perception of sleep 
problems in children of normal intelligence with pervasive developmental disorders: prevalence, 
severity, and pattern. Journal of American Academy of Child and Adolescent Psychiatry. 
2005;44(8):815-822. 
68. 
Wiggs L, Stores G. Behavioural treatment for sleep problems in children with severe intellectual 
disabilities and daytime challenging behaviour: Effect on mothers and fathers. British Journal of Health 
Psychology. 2001;6(3):257. 
69. 
Alfano CA, Ginsburg GS, Kingery JN. Sleep-related problems among children and adolescents with 
anxiety disorders. Journal of the American Academy of Child & Adolescent Psychiatry. 2007;46(2):224-
232. 
70. 
Scott N, Blair PS, Emond AM, et al. Sleep patterns in children with ADHD: a population‐ based cohort 
study from birth to 11 years. Journal of Sleep Research. 2013;22(2):121-128. 
71. 
Dahl R, Lewin D. Sleep and depression. In: G.Stores, L.Wiggs, eds. Sleep disturbance in children and 
adolescents with disorders of development: Its significance and management. New York: Cambridge 
University Press; 2001:161–168. 
72. 
Glod CA, Teicher MH, Hartman CR, Harakal T. Increased nocturnal activity and impaired sleep 
maintenance in abused children. Journal of the American Academy of Child & Adolescent Psychiatry. 
1997;36(9):1236-1243. 
73. 
Gregory AM, Caspi A, Eley TC, Moffitt TE, O’Connor TG, Poulton R. Prospective longitudinal 
associations between persistent sleep problems in childhood and anxiety and depression disorders in 
adulthood. Journal of Abnormal Child Psychology. 2005;33(2):157-163. 
74. 
Gregory AM, Rijsdijk FV, Dahl RE, McGuffin P, Eley TC. Associations between sleep problems, 
anxiety, and depression in twins at 8 years of age. Pediatrics. 2006;118(3):1124-1132. 
75. 
Harvey AG. Sleep and circadian rhythms in bipolar disorder: Seeking synchrony, harmony, and 
regulation. The American Journal of Psychiatry. 2008;165(7):820-829. 
76. 
El‐ Sheikh M, Buckhalt JA, Mark Cummings E, Keller P. Sleep disruptions and emotional insecurity 
are pathways of risk for children. Journal of Child Psychology and Psychiatry. 2007;48(1):88-96. 
77. 
Smaldone A, Honig JC, Byrne MW. Does assessing sleep inadequacy across its continuum inform 
associations with child and family health? Journal of Pediatric Health Care. 2009;23(6):394-404. 
78. 
Gregory AM, Van der Ende J, Willis TA, Verhulst FC. Parent-reported sleep problems during 
development and self-reported anxiety/depression, attention problems, and aggressive behavior later in 
life. Archives of pediatrics & adolescent medicine. 2008;162(4):330. 
79. 
Hemmi MH, Wolke D, Schneider S. Associations between problems with crying, sleeping and/or 
feeding in infancy and long-term behavioural outcomes in childhood: a meta-analysis. Archives of 
Disease in Childhood. 2011;96(7):622-629. 
80. 
Spoormaker VI, Montgomery P. Disturbed sleep in post-traumatic stress disorder: Secondary symptom 
or core feature? Sleep Medicine Reviews. 2008;12(3):169-184. 
81. 
Harb GC, Cook JM, Gehrman PR, Gamble GM, Ross RJ. Post-traumatic stress disorder nightmares and 
sleep disturbance in Iraq war veterans: a feasible and promising treatment combination. Journal of 
Aggression, Maltreatment & Trauma. 2009;18(5):516-531. 
82. 
Spilsbury JC. Sleep as a mediator in the pathway from violence-induced traumatic stress to poorer health 
and functioning: a review of the literature and proposed conceptual model. Behavioral sleep medicine. 
2009;7(4):223-244. 
83. 
Buysse D, Yu, L., Moul, D.E., Germain, A/. Stover, A., Dodds, N.E., Johnons, K.K., Shablesky-Cade, 
M.A., & Pilkonis, P. Development and validation of patient-reported outcome measures for sleep 
disturbance and sleep-related impairments. Sleep. 2010;33:1-12. 
84. 
Delahaye J, Kovacs E, Sikora D, et al. The relationship between Health-Related Quality of Life and 
sleep problems in children with Autism Spectrum Disorders. Research in Autism Spectrum Disorders. 
2014;8(3):292-303. 
85. 
Jan JE, Owens JA, Weiss MD, et al. Sleep Hygiene for Children With Neurodevelopmental Disabilities. 
Pediatrics. 2008;122(6):1343-1350. 

Version 1.2: 7-12-2018                                                                                                                                  Page 22 of 27 
86. 
Owens JA. Classification and epidemiology of childhood sleep disorders. Sleep Medicine Clinics. 
2007;2(3):353-361. 
87. 
Adkins KW, Goldman SE, Fawkes D, et al. A pilot study of shoulder placement for actigraphy in 
children. Behavioral sleep medicine. 2012;10(2):138-147. 
88. 
Goldman SE, McGrew S, Johnson K, Richdale A, Clemons T, Malow B. Sleep is associated with 
problem behaviors in children and adolescents with autism spectrum disorders. Research in Autism 
Spectrum Disorders. 2011;5:1223-1229. 
89. 
Goldman SE, Richdale AL, Clemons T, Malow BA. Parental sleep concerns in autism spectrum 
disorders: Variations from childhood to adolescence. Journal of Autism and Developmental Disorders. 
2012;42(4):531-538. 
90. 
Krakowiak P, Goodlin-Jones B, Hertz‐ Piccioto I, Croen LA, Hansen RL. Sleep problems in children 
with autism spectrum disorders, developmental delays, and typical development: a population‐ based 
study. Journal of Sleep Research. 2008;17(2):197-206. 
91. 
Polimeni MA, Richdale AL, Francis AJ. A survey of sleep problems in autism, asperger's disorder and 
typically developing children. Journal of Intellectual Disability Research. 2005;49(Pt 4):260-268. 
92. 
Richdale AL, Prior MR. The sleep/wake rhythm in children with autism. European Child and 
Adolescent Psychiatry. 1995;4(3):175-186. 
93. 
Richdale AL, Schreck KA. Sleep problems in autism spectrum disorders: Prevalence, nature, and 
possible biopsychosocial aetiologies. Sleep Medicine Reviews. 2009;13(6):403-411. 
94. 
Souders MC, Mason TB, Valladares O, et al. Sleep behaviors and sleep quality in children with autism 
spectrum disorders. Sleep. 2009;32(12):1566-1578. 
95. 
Turner KS, Johnson CR. Behavioral interventions to address sleep disturbances in children with autism 
spectrum disorders: A review. Topics in Early Childhood Special Education. 2012;33(3):144-152. 
96. 
Vriend JL, Corkum PV, Moon EC, Smith IM. Behavioral interventions for sleep problems in children 
with autism spectrum disorders: current findings and future directions. Journal of Pediatric Psychology. 
2011;36(9):1017-1029. 
97. 
Johnson CR, Turner KS, Foldes E, Brooks MM, Kronk R, Wiggs L. Behavioral parent training to 
address sleep disturbances in young children with autism spectrum disorder: a pilot trial. Sleep 
Medicine. 2013;14(10):995-1004. 
98. 
Allik H, Larsson JO, Smedje H. Sleep patterns of school-age children with asperger syndrome or high-
functioning autism. Journal of Autism and Developmental Disorders. 2006;36(5):585-595. 
99. 
Henderson JA, Barry TD, Bader SH, Jordan SS. The relation among sleep, routines, and externalizing 
behavior in children with an autism spectrum disorder. Research in Autism Spectrum Disorders. 
2011;5(2):758-767. 
100. 
Ibrahim SH, Voigt RG, Katusic SK, Weaver AL, Barbaresi WJ. Incidence of gastrointestinal symptoms 
in children with Autism: A population-based study. Pediatrics. 2009;124(2):680-686. 
101. 
Reynolds AM, Malow BA. Sleep and autism spectrum disorders. Pediatric Clinics of North America. 
2011;58(3):685-698. 
102. 
Liu X, Hubbard JA, Fabes RA, Adam JB. Sleep disturbances and correlates of children with autism 
spectrum disorders. Child Psychiatry & Human Development. 2006;37(2):179-191. 
103. 
Malow BA. Sleep disorders, epilepsy, and autism. Mental Retardation and Developmental Disabilities 
Research Reviews. 2004;10(2):122-125. 
104. 
Melmed R, Schneider C, Fabes R, Phillips J, Reichelt K. Metabolic markers and gastrointestinal 
symptoms in children with autism and related disorders. Journal of Pediatric Gastroenterology and 
Nutrition. 2000;31:S31–32. 
105. 
Valicenti-McDermott M, McVicar K, Rapin I, Wershil BK, Cohen H, Shinnar S. Frequency of 
gastrointestional symptoms in children with autistic spectrum disorders and association with family 
histry of autoimmune disease. Journal of Developmental and Behavioiral Pediatrics. 2006;27(2):S128-
136. 
106. 
Mazurek MOP, G.F. Sleep problems in childrne with autism spectrum disorder:  Eamining the 
contributions of sensory over-responsivity and anxiety. Sleep Medicine. 2015;16:270-279. 

Version 1.2: 7-12-2018                                                                                                                                  Page 23 of 27 
107. 
Stores G, Wiggs L. Clinical services for sleep disorders. Archives of Disease in Childhood. 
1998;79(6):495-497. 
108. 
Malow BA, McGrew SG. Sleep disturbances and autism. Sleep Medicine Clinics. 2008;3(3):479-488. 
109. 
Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-
analysis. Developmental Medicine & Child Neurology. 2011;53(9):783-792. 
110. 
Tordjman S, Anderson GM, Pichard N, Charbuy H, Touitou Y. Nocturnal excretion of 6-
sulphatoxymelatonin in children and adolescents with autistic disorder. Biological Psychiatry. 
2005;57(2):134-138. 
111. 
Tordjman S, Anderson GM, Bellissant E, et al. Day and nighttime excretion of 6-sulphatoxymelatonin in 
adolescents and young adults with autistic disorder. Psychoneuroendocrinology. 2012;37(12):1990-
1997. 
112. 
Gabriels RL, Cuccaro ML, Hill DE, Ivers BJ, Goldson E. Repetitive behaviors in autism: relationships 
with associated clinical features. Research in Developmental Disabilities. 2005;26(2):169-181. 
113. 
Goldman SE, Surdyka K, Cuevas R, Adkins K, Wang L, Malow BA. Defining the sleep phenotype in 
children with autism. Developmental neuropsychology. 2009;34(5):560-573. 
114. 
Malow BA, Marzec ML, McGrew SG, Wang L, Henderson LM, Stone WL. Characterizing sleep in 
children with autism spectrum disorders: a multidimensional approach. Sleep. 2006;29(12):1563-1571. 
115. 
Schreck KA, Williams K, Smith AF. A comparison of eating behaviors between children with and 
without Autism. Journal of Autism and Developmental Disorders. 2004;34(4):433-438. 
116. 
Mayes SD, Calhoun SL. Variables related to sleep problems in children with autism. Research in Autism 
Spectrum Disorders. 2009;3(4):931-941. 
117. 
Mazurek MO, Sohl K. Sleep and behavioral problems in children with autism spectrum disorder. 
Journal of Autism and Developmental Disorders. 2016;46(6):1906-1915. 
118. 
Richdale AL, Schreck KA. Sleep problems in autism spectrum disorders: prevalence, nature, & possible 
biopsychosocial aetiologies. Sleep Med Rev. 2009;13(6):403-411. 
119. 
Hollway JA, Aman MG. Sleep correlates of pervasive developmental disorders: a review of the 
literature. Research in Developmental Disabilities. 2011;32(5):1399-1421. 
120. 
Williams PG, Sears LL, Allard A. Sleep problems in children with autism. Journal of Sleep Research. 
2004;13(3):265-268. 
121. 
Lopez-Wagner MC, Hoffman CD, Sweeney DP, Hodge D, Gilliam JE. Sleep problems of parents of 
typically developing children and parents of children with autism. The Journal of Genetic Psychology. 
2008;169(3):245-259. 
122. 
Meltzer LJ. Brief report: sleep in parents of children with autism spectrum disorders. Journal of 
Pediatric Psychology 2008;33(4):380-386. 
123. 
Meltzer LJ, Mindell JA. Relationship between child sleep disturbances and maternal sleep, mood, and 
parenting stress: a pilot study. Journal of Family Psychology. 2007;21(1):67-73. 
124. 
Meltzer LJ. Factors associated with depressive symptoms in parents of children with autism spectrum 
disorders. Research in Autism Spectrum Disorders. 2011;5(1):361-367. 
125. 
Doyen C, Mighiu D, Kaye K, et al. Melatonin in children with autistic spectrum disorders: recent and 
practical data. European Child and Adolescent Psychiatry. 2011;20(5):231-239. 
126. 
Guénolé F, Godbout R, Nicolas A, Franco P, Claustrat B, Baleyte J-M. Melatonin for disordered sleep in 
individuals with autism spectrum disorders: Systematic review and discussion. Sleep Medicine Reviews. 
2011;15(6):379-387. 
127. 
Giannotti F, Cortesi F, Cerquiglini A, Bernabei P. An open-label study of controlled-release melatonin 
in treatment of sleep disorders in children with autism. Journal of Autism and Developmental Disorders. 
2006;36(6):741-752. 
128. 
Wasdell MB, Jan JE, Bomben MM, et al. A randomized, placebo-controlled trial of controlled release 
melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with 
neurodevelopmental disabilities. Journal of pineal research. 2008;44(1):57-64. 

Version 1.2: 7-12-2018                                                                                                                                  Page 24 of 27 
129. 
Braam W, Didden R, Smits M, Curfs L. Melatonin treatment in individuals with intellectual disability 
and chronic insomnia: a randomized placebo‐ controlled study. Journal of Intellectual Disability 
Research. 2008;52(3):256-264. 
130. 
Wright B, Sims D, Smart S, et al. Melatonin versus placebo in children with autism spectrum conditions 
and severe sleep problems not amenable to behaviour management strategies: a randomised controlled 
crossover trial. Journal of Autism and Developmental Disorders. 2011;41(2):175-184. 
131. 
Harrington JW, Rosen L, Patrick PA. Parental perceptions and use of complementary and alternative 
medicine practices for children with autistic spectrum disorders in private practice. Developmental and 
Behavioral Pediatrics. 2006(27):S156-S161. 
132. 
Andersen I, Kaczmarska J, McGrew S, Malow B. Melatonin for insomnia in children with autism 
spectrum disorders. Journal of Child Neurology. 2008;23(5):482-485. 
133. 
Malow B, Adkins KW, McGrew SG, et al. Melatonin for sleep in children with autism: a controlled trial 
examining dose, tolerability, and outcomes. Journal of Autism and Developmental Disorders. 
2012;42(8):1729-1737. 
134. 
Mindell JA, Emslie G, Blumer J, et al. Pharmacologic Management of Insomnia in Children and 
Adolescents: Consensus Statement. Pediatrics. 2006;117(6):e1223-1232. 
135. 
Malow BA, Byars K, Johnson K, et al. A practice pathway for the identification, evaluation, and 
management of insomnia in children and adolescents with autism spectrum disorders. Pediatrics. 
2012;130 Suppl 2:S106-124. 
136. 
Durand VM, Gernert-Dott P, Mapstone E. Treatment of sleep disorders in children with developmental 
disabilities. Journal of the Association of Persons with Severe Handicap. 1996;21:114–122. 
137. 
Durand VM. Treating Sleep Terrors in Children with Autism. Journal of Positive Behavior 
Interventions. 2002;4(2):66-72. 
138. 
Wolf MM, Risley T, Meese H. Application of operant conditioning procedures to the behavior problems 
of an autistic child. Behavior Research and Therapy. 1963;1(2):305-312. 
139. 
Christodulu K, Durand VM. Reducing bedtime disturbance and night waking using positive bedtime 
routines and sleep restriction. Focus on Autism and Other Developmental Disabilities. 2004;19(3):130-
139. 
140. 
Durand VM, Christodulu K. Description of a sleep-restriction program to reduce bedtime disturbances 
and night waking. Journal of Positive Behavior Interventions. 2004;6(2):83-91. 
141. 
Weiskop S, Richdale A, Matthews J. Behavioural treatment to reduce sleep problems in children with 
autism or fragile X syndrome. Developmental Medicine & Child Neurology. 2005;47(2):94-104. 
142. 
Mindell JA, Kuhn B, Lewin DS, Meltzer LJ, Sadeh A. Behavioral treatment of bedtime problems and 
night wakings in infants and young children. Sleep. 2006;29(10):1263-1276. 
143. 
Piazza CC, Fisher WW, Sherer M. Treatment of multiple sleep problems in children with developmental 
disabilities: faded bedtime with response cost versus bedtime scheduling. Developmental Medicine & 
Child Neurology. 1997;39(6):414-418. 
144. 
Wiggs L, Stores G. Behavioural treatment for sleep problems in children with severe learning 
disabilities and challenging daytime behaviour: Effect on sleep patterns of mother and child. Journal of 
Sleep Research. 1998;7(2):119-126. 
145. 
Weiskop S, Matthews J, Richdale A. Treatment of sleep problems in a 5-year-old boy with autism using 
behavioural principles. Autism. 2001;5(2):209-221. 
146. 
Montgomery P, Stores G, Wiggs L. The relative efficacy of two brief treatments for sleep problems in 
young learning disabled (mentally retarded) children: a randomised controlled trial. Archives of Disease 
in Childhood. 2004;89(2):125-130. 
147. 
Moon E, Corkum P, Smith I. Case study: A case-series evaluation of a behavioral sleep intervention for 
three children with autism and primary insomnia. Journal of Pediatric Psychology. 2010;36(1):47-54. 
148. 
Aman MG, McDougle CJ, Scahill L, et al. Medication and parent training in children with pervasive 
developmental disorders and serious behavior problems: results from a randomized clinical trial. Journal 
of American Academy of Child and Adolescent Psychiatry. 2009;48(12):1143-1154. 

Version 1.2: 7-12-2018                                                                                                                                  Page 25 of 27 
149. 
Scahill L, McDougle CJ, Aman MG, et al. Effects of Risperidone and parent training on adaptive 
functioning in children With pervasive developmental disorders and serious behavioral problems. 
Journal of the American Academy of Child and Adolescent Psychiatry. 2012;51(2):136-146. 
150. 
Whittingham K, Sofronoff K, Sheffield J, Sanders M. Stepping Stones Triple P: an RCT of a parenting 
program with parents of a child diagnosed with an Autism Spectrum Disorder. Journal of Abnormal 
Child Psychology. 2009;37(4):469-480. 
151. 
Aman MG, McDougle CJ, Scahill L, et al. Medication and parent training in children with pervasive 
developmental disorders and serious behavior problems: results from a randomized clinical trial. Journal 
of American Academy of Child and Adolescent Psychiatry. 2009;48(12):1143-1154. 
152. 
Solomon M, Ono M, Timmer S, Goodlin-Jones B. The effectiveness of parent child interaction therapy 
for families of children on the autism spectrum. Journal of Autism and Developmental Disorders. 
2008;38(9):1767-1776. 
153. 
Tonge BJ, Brereton A, Kiomall M, MacKinnon A, King N, Rinehart N. Effects on parental mental 
health of an education and skills training program for parents of young children with autism: a 
randomized controlled trial. Journal of American Academy of Child and Adolescent Psychiatry. 
2006;45(5):561-569. 
154. 
Scahill L, Bearss K, Lecavalier L, et al. Effect of parent training on adaptive behavior in children with 
autism spectrum disorder and disruptive behavior: results of a randomized trial. Journal of the American 
Academy of Child & Adolescent Psychiatry. 2016;55(7):602-609. 
155. 
Smith T, Scahill L, Dawson G, et al. Designing research studies on psychosocial interventions in autism. 
Journal of Autism and Developmental Disorders. 2007;37:354-366. 
156. 
Cortesi F, Giannotti F, Sebastiani T, Panunzi S, Valente D. Controlled-release melatonin, singly and 
combined with cognitive behavioural therapy, for persistent insomnia in children with autism spectrum 
disorders: a randomized placebo-controlled trial. Journal of Sleep Research. 2012;21(6):700-709. 
157. 
Malow B, Adkins K, Reynolds A, et al. Parent-Based Sleep Education for Children with Autism 
Spectrum Disorders. Journal of Autism and Developmental Disorders. 2014;44(1):216-228. 
158. 
Dudding CC. Digital videoconferencing: Applications across the disciplines. Communication Disorders 
Quarterly. 2009;30(3):178-182. 
159. 
Ingersoll B, Wainer AL, Berger NI, Pickard KE, Bonter N. Comparison of a self-directed and therapist-
assisted telehealth parent-mediated intervention for children with ASD: A pilot RCT. Journal of autism 
and developmental disorders. 2016;46(7):2275-2284. 
160. 
Vismara LA, McCormick C, Young GS, Nadhan A, Monlux K. Preliminary findings of a telehealth 
approach to parent training in autism. Journal of Autism and Developmental Disorders. 
2013;43(12):2953-2969. 
161. 
Wacker DP, Lee JF, Dalmau YCP, et al. Conducting functional communication training via telehealth to 
reduce the problem behavior of young children with autism. Journal of developmental and physical 
disabilities. 2013;25(1):35-48. 
162. 
Suess AN, Wacker DP, Schwartz JE, Lustig N, Detrick J. Preliminary evidence on the use of telehealth 
in an outpatient behavior clinic. Journal of applied behavior analysis. 2016;49(3):686-692. 
163. 
Pickard KE, Wainer AL, Bailey KM, Ingersoll BR. A mixed-method evaluation of the feasibility and 
acceptability of a telehealth-based parent-mediated intervention for children with autism spectrum 
disorder. Autism. 2016;20(7):845-855. 
164. 
Johnson C, Foldes, E., Demand, A. Relationship between sleep of children with autism spectrum 
disorder and parental sleep quality. in preparation. 
165. 
Sivertsen B, Posserud MB, Gillberg C, Lundervold AJ, Hysing M. Sleep problems in children with 
autism spectrum problems: a longitudinal population-based study. Autism. 2012;16(2):139-150. 
166. 
Blunden S, Lushington K, Lorenzen B, Martin J, Kennedy D. Neuropsychological and psychosocial 
function in children with a history of snoring or behavioral sleep problems. The Journal of Pediatrics. 
2005;146(6):780-786. 

Version 1.2: 7-12-2018                                                                                                                                  Page 26 of 27 
167. 
Ebert JCS, Drake AF. The impact of sleep-disordered breathing on cognition and behavior in children: 
A review and meta-synthesis of the literature. Otolaryngology - Head and Neck Surgery. 
2004;131(6):814. 
168. 
Mindell JA, Emslie G, Blumer J, et al. Pharmacologic management of insomnia in children and 
adolescents: consensus statement. Pediatrics. 2006;117(6):e1223-1232. 
169. 
Robins DL, Casagrande K, Barton M, Chen CM, Dumont-Mathieu T, Fein D. Validation of the 
Modified Checklist for Autism in Toddlers, revised with follow-up (M-CHAT-R/F). Pediatrics. 
2014;133(1):37-45. 
170. 
Rutter M, Bailey A, Lord C. The Social Communication Questionnaire: Manual. Torrance, CA: Western 
Psychological Services; 2003. 
171. 
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture 
(REDCap)—a metadata-driven methodology and workflow process for providing translational research 
informatics support. Journal of biomedical informatics. 2009;42(2):377-381. 
172. 
Guy W. Dosage Record and Treatment Emergent Symptoms Scale. ECDEU Assessment Manual for 
Psychopharmacology (Revised). Rockville, MD.: US Department of Health, Education and Human 
Welfare publication (ADM); 1976:223-244. 
173. 
Simonds J, Parraga H. Prevalence of sleep disorders and sleep behaviors in children and adolescents. 
Journal of American Academy of Child and Adolescent Psychiatry. 1982;21:383-388. 
174. 
Spruyt K, Gozal D. Pediatric sleep questionnaire as diagnostic and epidemiological tools: A review of 
currently available instruments. Sleep Medicine Reviews. 2011;15:19-32. 
175. 
Wiggs L, Stores G. Severe sleep disturbances and daytime challenging behavior in children with severe 
learning disabilities. Journal of Intellectual Disability Research. 1996;40:518-528. 
176. 
Maas A, Didden R, Korzilius H, et al. Psychometric properties of a sleep questionnaire for use in 
individuals with intellectual disabilities. Research in Developmental Disabilities. 2011;32:2467-2479. 
177. 
Scahill L, McCracken JT, King BH, et al. Extended-release guanfacine for hyperactivity in children with 
autism spectrum disorder. American Journal of Psychiatry. 2015;172(12):1197-1206. 
178. 
Aman MG, Singh NN, Stewart AW, Field CJ. Psychometric characteristics of the Aberrant Behavior 
Checklist. American Journal of Mental Deficiency. 1985;89(5):492-502. 
179. 
Aman MG, Singh NN, Stewart AW, Field CJ. The aberrant behavior checklist: A behavior rating scale 
for the assessment of treatment effects. American Journal of Mental Deficiency. 1985;89(5):485-491. 
180. 
Shea S, Turgay A, Carroll A, et al. Risperidone in the treatment of disruptive behavioral symptoms in 
children with autistic and other pervasive developmental disorders. Pediatrics. 2004;114(5):e634-e641. 
181. 
King BH, Hollander E, Sikich L, et al. Lack of efficacy of citalopram in children With autism spectrum 
disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Archives 
of General Psychiatry. 2009;66(6):583-590. 
182. 
Network RUoPPRA. Risperidone in children with autism and serious behavioral problems. New 
England Journal of Medicine. 2002;347:314-321. 
183. 
Network R. Risperidone treatment of autistic disorder: Longer term benefits and blinded discontinuation 
after six months. American Journal of Psychiatry 2005;162(7):1361-1369. 
184. 
Aman MG, Singh NN. Aberrant Behavior Checklist Manual, Second Edition. East Aurora, NY: Slosson 
Educational Publications, Inc.; 2017. 
185. 
Abidin R. Parenting Stress Index (3rd ed.). Lutz, FL: Psychological Assessment Resources; 1995. 
186. 
Hassall R, Rose J, McDonald J. Parenting stress in mothers of children with an intellectual disability: the 
effects of parental cognitions in relation to child characteristics and family support. Journal of 
Intellectual Disability Research. 2005;49(6):405-418. 
187. 
Montes G, Halterman JS. Characteristics of school-age children with autism. Journal of Developmental 
and Behavioral Pediatrics. 2006;27(5):379-385. 
188. 
Wolery M, Garfinkle AN. Measures in intervention research with young children who have autism. 
Journal of Autism and Developmental Disorders. 2002;32(5):463. 
189. 
Tomanik S, Harris GE, Hawkins J. The relationship between behaviours exhibited by children with 
autism and maternal stress. Journal of intellectual & developmental disability. 2004;29(1):16-26. 

Version 1.2: 7-12-2018                                                                                                                                  Page 27 of 27 
190. 
Postorino V, Gillespie S, Lecavalier L, et al. Clinical correlates of parenting stress in children with 
Autism Spectrum Disorder and serious behavioral problems. Journal of Child and Adolescent 
Psychology. In press. 
191. 
Johnson C, Foldes E, DeMand A, Brooks M. Behavioral Parent Training to Address Feeding Problems 
in Children with Autism Spectrum Disorder: A Pilot Trial. Journal of Developmental and Physical 
Disabilities. 2015:1-17. 
192. 
Kroenke K, Strine TW, Spitzer RL, Williams JB, Berry JT, Mokdad AH. The PHQ-8 as a measure of 
current depression in the general population. Journal of affective disorders. 2009;114(1):163-173. 
193. 
Gibaud-Wallson J, Wandersman LP. Development and utility of the Parenting Sense of Competence 
Scale. Paper presented at: American Psychological Association1978; Toronto. 
194. 
Gilmore L, Cuskelly M. Factor structure of the Parenting Sense of Competence scale using a normative 
sample. Child: Care, health and development. 2009;35(1):48-55. 
195. 
Iadarola S, Levato L, Harrison B, et al. Teaching parents behavioral strategies for ASD: Effects on 
stress, strain and competence. Journal of Autism and Developmental Disorders. In press. 
196. 
Buysse DJ, Reynolds III CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a 
new instrument for psychiatric practice and research. Psychiatry research. 1989;28(2):193-213. 
197. 
Johnson CR, Handen BL, Butter E, et al. Development of a parent training program for children with 
pervasive developmental disorders. Behavioral Interventions. 2007;22(3):201-221. 
198. 
Bearss K, Johnson C, Handen B, Smith T, Scahill L. A pilot study of parent training in young children 
with autism spectrum disorders and disruptive behavior. Journal of Autism and Developmental 
Disorders. 2013;43(4):829-840. 
199. 
Gurka MJ. Selecting the best linear mixed model under REML. The American Statistician. 
2006;60(1):19-26. 
200. 
Kenward MG, Roger JH. Small sample inference for fixed effects from restricted maximum likelihood. 
Biometrics. 1997:983-997. 
201. 
Molenberghs G TH, Jansen I, Beunckens C, Kenward MG, Mallinckrodt C, Carroll RJ. Analyzing 
incomplete longitudinal clincal trial data. Biostatiscis. 2004;5(3):445-464. 
202. 
Carpenter JR, Kenward MG. Missing data in randomised controlled trials-a practical guide. Medical 
Statistics Unit, London School of Hygiene & Tropical Medicine: London School of Hygiene & Tropical 
Medicine. 2007.