Online Mindfulness Intervention for Adolescents With 22q11DS
Phase: NA
Conditions: 22Q11 Deletion Syndrome
Sponsor: Innovation Research & Training

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Study Protocol and Statistical Analysis Plan 
 
Title of Study: Online Mindfulness Training for Adolescents with 22q11.2 Deletion Syndrome 
ClinicalTrial.gov Identifier: NCT05849441 
Principal Investigators: Alison Parker, PhD 
Co-Investigator: Janis Kupersmidt, PhD 
Date of Document: 03-06-2023 
 
 
 
 
 
 

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Table of contents 
 
Page number 
Study Protocol 
3 
  Objectives  
3 
  Design 
3 
  Methods 
3 
Statistical Analysis Plan 
8 
 
 

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Study Protocol 
 
Objectives:  
 
To date, there are very few non-pharmacological, behavioral interventions that have been 
developed and evaluated specifically for adolescents with chromosome 22q11.2 deletion 
syndrome (22q11DS). Thus, there is a need for effective interventions that are tailored for this 
population to improve their health and well-being. Practicing mindfulness on a daily basis is one 
possible avenue to build self-regulatory abilities and has been associated with beneficial health 
outcomes. The Aware Program is an online mindfulness education program for adolescents with 
22q11DS designed to enhance their coping skills and ability to manage stress and anxiety in 
healthy ways. The main objective of the study is to test the effectiveness of the Aware Program 
with adolescents with 22q11DS and their parents. This study will examine if the Aware Program 
increases adolescents’ use of healthy coping strategies, emotion regulation abilities, and global 
health, as well as reduces adolescents’ anxiety and executive functioning difficulties. 
 
Design: 
 
The study is a parallel group randomized controlled trial with a 1:1 allocation ratio and 
superiority framework to test the efficacy of the Aware Program among parent-adolescent pairs. 
The randomized controlled trial will be conducted online at two time points: 1) baseline/pre-test 
and 2) post-test (four weeks after pre-test). The study questionnaires will be programmed into an 
online data collection system and the intervention itself is also completed online. 
 
Participants will be randomized to one of two conditions: 1) intervention (pairs will receive 
access to the Aware Program right away) or 2) wait-list control (pairs will not have access to the 
intervention between pre-test and post-test assessments; after completing the post-test 
questionnaire, pairs will be given the option to use the Aware Program).  
 
Participants are randomized and enrolled based on: 1) time study forms (e.g., consent) were 
completed and 2) confirmation of email addresses. A statistician will generate the allocation 
sequences using a random number generator in Excel.  After eligibility is determined, the PI will 
assign participants to condition (either intervention or wait-list control) according to those 
sequences and then enroll participants in the study. All participants will be assigned a unique ID 
number that will be associated with their data in place of a name.  
 
Methods:  
 
Sample and Recruitment. Sixty (N = 60) parent-adolescent pairs (adolescents with 
22q11DS between the ages of 12 and 19 years) will be recruited to participate in the study. To be 
eligible to participate in the study, adolescents must: 1) Have received a diagnosis of 22q11.2 
Deletion Syndrome; 2) be between the ages of 12 and 19 years old; 3) have an IQ of greater than 
or equal to 55; 4) have regular internet and computer access; 5) speak and read English (all study 
and program materials are in English). To be included in the study, parents must: 1) Have a 
participating adolescent in the study and 2) read fluently in English (all study and program 
materials are in English). Only one parent per youth may participate. Parent-adolescent pairs will 

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be recruited from across the United States. A study recruitment website will contain information 
about the research study that interested parent-adolescent pairs can review. The website will also 
have the study team contact information and a link to the eligibility screening questionnaire. 
Parent-adolescent pairs will also be recruited via a study flyer and with the help of expert 
consultants, as well as help from organizations that work with families of individuals with 
22q11DS and diagnostic clinics or centers that specialize in 22q11DS. Recruitment materials 
may also be shared on social media, through word of mouth, via email listservs, and other online 
methods in order to reach families of adolescents with 22q11DS. 
 
Procedure.  Interested parents and adolescents will visit the recruitment website to learn 
more and respond to the study eligibility questions. Parents will be notified onscreen 
immediately if the pair is eligible to participate in the study, and if so, they will then be provided 
with a link to the electronic study forms to review and sign.  For adolescents aged 12-17 years 
and their parents: The parent will be asked to complete a parent permission and consent form and 
adolescents will be asked to complete a youth assent form. For youth aged 18 and 19 years and 
their parents: Prior to reviewing the forms, parents of 18- and 19-year-olds will be asked to 
respond to the following question: “Is there legal guardianship in place between you and your 
teen?”. If there is a legal guardianship in place, the parent will be asked to complete the parent 
permission and consent form and the adolescent will be asked to complete the youth assent form.  
If there is not a legal guardianship in place, the parent will be asked to complete the parent 
consent form and the adolescent will be asked to sign a youth consent form. The permission, 
consent, and assent forms will describe the goals of the study, as well as the minor potential risks 
and the benefits of participation. Permission, consent, and assent forms will also state the 
participant may discontinue their participation at any time. Potential parent-adolescent pairs will 
be provided with the contact information of the researchers and may contact them to ask any 
questions they may have about the study. Parent-adolescent pairs will read the permission, 
consent, and assent forms and provide online permission, consent, and assent by typing their 
names into a text box, providing contact information, and clicking a button to indicate 
permission/consent/assent rather than providing a signed hard copy of the forms. They will have 
the option to download and/or print the forms to retain a copy for their files. Only parent-
adolescent pairs with completed study forms will be permitted to participate in the study. 
After completing and submitting the study forms, parents will receive an email 
confirmation that will ask parents to confirm their email address in order to receive emails about 
the study. If parents do not confirm their email address, reminders will be sent to parents via 
iRT’s study management system.  iRT project staff will determine whether or not the address the 
parent has provided for the pair in the consent forms is real using a Google map search. Eligible 
parent-adolescent pairs who have completed all study forms and confirmed their email address 
will receive a welcome email that will provide more information on the timeframe and tasks for 
the study. Participating parent-adolescent pairs will be randomly assigned to either the 
intervention group (immediate access to Aware Program) or the wait-list control group (delayed 
access to program). When the study starts, parent-adolescent pairs will receive an enrollment 
email from iRT’s study management system via the parent’s email address with a link for the 
participating parent to complete the online parent pretest questionnaire within one week. This 
enrollment email will also indicate that the parent will receive a second message with a unique 
link for their adolescents to use to complete the online teen pretest questionnaire within one 
week. Completion of the pretest questionnaires may take up to 30 minutes for participants.  Upon 

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completion of the pretest questionnaires, parent-adolescent pairs will see a message at the end of 
the questionnaire indicating that the parent will receive an email regarding the pair’s next steps 
in the research study.  
• Pairs in the intervention group will receive an email that they are able to access the 
Aware Program immediately with instructions on how to access and review the 
Aware Program. There are four courses in the Aware Program and each course has 5 
brief lessons. It is expected that adolescents will complete one course per week. For 
the purposes of the study, adolescents (and their caregivers) will be instructed that 
they have four weeks to complete the Aware Program but that it can be done at their 
own pace and schedule. Parents will have access to the parent resources as part of the 
program. Parent-adolescent pairs may also subscribe to the mobile messaging service 
associated with the Aware program; this optional service includes progress reminders, 
encouragement, and practice content sent to their phones. The mobile messages will 
not be sent after 9pm or before 8am, and families may opt out at any time from their 
phone by texting “STOP” in response to a message. Parents may opt their teen and 
themselves in mobile messaging from the parent dashboard, as well as opt out if 
needed. 
• Pairs in the wait-list control group will receive an email telling them that they will be 
asked to complete another set of questionnaires in about four weeks.  Participants in 
the wait-list control group will not have access the Aware Program during this time 
and will receive business as usual, which in this case is no mindfulness education. 
The wait-list control group will later receive access to the Aware Program once they 
have completed the posttest questionnaires.  
 
Project staff members will monitor usage of the Aware Program through iRT’s Learning 
Management System (LMS).  Approximately five weeks after completing the pretest 
questionnaire, participating parents will receive an email with a link for the parent to access the 
online parent posttest questionnaire to be completed within one week. This parent email will also 
indicate that the parent will receive another message with a unique link for their adolescents to 
use to complete the online teen posttest questionnaire within one week. Completion of the 
posttest questionnaires may take up to 30 minutes for participants. Participants in the 
intervention group will receive the Consumer Satisfaction Questionnaire at the end of their 
posttest questionnaire. Completion of the Consumer Satisfaction Questionnaire may take 
approximately 15 minutes.  Participants in the wait-list control group will have the option of 
reviewing the Aware Program after their posttest data have been collected. Adolescents will have 
access to the four courses and parents will have access to the parent dashboard, in which parents 
can opt in or out of mobile messages for themselves and their teens. After 4 weeks, the wait-list 
control group will have the opportunity to complete the Consumer Satisfaction Questionnaire 
about the Aware Program. Completion of the Consumer Satisfaction Questionnaires by 
participants in the wait-list control group is optional and those participants will not receive an 
incentive for completing these questionnaires. Parents (in the wait-list control group) will receive 
an email with a link for the parent to access the online parent Consumer Satisfaction 
Questionnaire to be completed within one week. This email will also indicate that the parent will 
receive another message with a unique link for their adolescents to use to complete the online 
teen Consumer Satisfaction Questionnaire within one week. Participants will receive automatic 
email reminders from the study management system if they have not completed the 

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questionnaires or not accessed the Aware Program. The research team will also call a parent or 
send a check-in email to a parent if there is no response following the automatic reminders. 
Incentives for completing the pretest questionnaires and for completing the posttest 
questionnaires will be physically mailed to parent-adolescent pairs using the address provided on 
their study forms. At the end of the study, responses on the online questionnaires will be 
downloaded from the online data collection system and saved on a secure, password-protected 
network in preparation for statistical analyses. 
 
Measures.  
 
Adolescents: 
 
Background information. Adolescents will be asked to provide some basic demographic 
information (e.g., age, gender, race, ethnicity).  
 
Self-Report Coping Measure (SRCM; Causey & Dubow, 1992) assesses coping in response to 
stressors across five coping domains (e.g., Seeking Social Support, Problem Solving, Distancing, 
Externalizing, and Internalizing). Adolescents will respond to 34 items on a 5-point Likert scale 
(1 = Never to 5 = Always) to indicate how often they use a given coping strategy (e.g., “Try to 
think of different ways to solve it) when facing stress. Additionally, 3 items related to 
mindfulness skills (e.g., “Stop and notice how I am feeling”) will be included as a mindfulness 
subscale in this measure.  
 
Emotion Regulation Questionnaire (ERQ; Gross & John, 2003) assesses differences in the use of 
two emotion regulation strategies: Cognitive Reappraisal and Suppression. Adolescents will 
respond to 10 items (e.g., “I keep my emotions to myself”) using a 7-point Likert rating scale (1 
= Strongly disagree to 7 = Strongly agree).  
 
Emotional Self-Efficacy Scale for Youth (Youth-ESES; Qualter et al., 2015) assesses youth’s 
beliefs about their ability to understand and manage emotions in themselves and others. 
Adolescents will rate their confidence in each of the 27 items (e.g., “I can tell when my feelings 
change”) using a 5-point Likert Scale (1 = Not at all confident to 5 = Very confident). The 
measure has four factors: Using and managing your own emotions; Identifying and 
understanding your own emotions; Dealing with emotions in others; Perceiving emotion through 
facial expressions and body language.  
 
Generalized Anxiety Disorder (GAD-7; Spitzer, Kroenke, Williams, & Lowe, 2006) assesses 
general anxiety in youth. Adolescents will respond to 7 items (e.g., “Over the last two weeks, 
how often have you been bothered by the following problems… feeling nervous, anxious, or on 
edge,”) using a 4-point Likert scale (0 = Not at all, 1 = Several days, 2 = More than half the days, 
3 = Nearly every day).  
 
Social Anxiety Scale for Adolescents (SAS-A; La Greca & Lopez, 1998) assesses social anxiety 
in youth. Adolescents will respond to 18 items (e.g., It’s hard for me to ask others to do things 
with me) using a 5-point Likert scale (1 = Not at all, 5 = All the time). The measure has three 

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factors: Fear of Negative Evaluation, Social Avoidance and Distress-New; Social Avoidance and 
Distress – General.  
 
PROMIS Pediatric Global Health Measure (PGH-7; Forrest, Bevans, Pratiwadi, Moon, Teneralli, 
Minton, & Tucker, 2014) assesses overall health and wellbeing across 7 items. Adolescents will 
respond to 4 items (e.g., In general, would you say your quality of life is…) using a 5-point 
Likert scale (5 = Excellent, 1 = Poor); 1 item (e.g., How often do you feel really sad) using a 5-
point Likert scale (5 = Never; 1 = Always); and 2 items (e.g., How often do you have fun with 
friends?) using a 5-point Likert scale (5 = Always; 1 = Never).  
 
Parents:  
 
Background information. Parents will be asked to provide some basic demographic information 
(e.g., age, gender, race, ethnicity, personality).   
 
The Emotion Regulation Checklist (Shields & Cicchetti, 1997) assesses parent reports of their 
adolescents’ emotion regulatory abilities. Parents will respond to 24 items (e.g., “Responds 
positively to neutral or friendly overtures by peers) on a 4-point Likert scale (1 = Never; 4 = 
Always). There are two subscales: Emotion Regulation (e.g., appropriate displays of emotion, 
awareness of emotions) and Negativity (e.g., lack of flexibility and regulation of emotion).  
 
Childhood Executive Functioning Inventory (Thorell & Nyberg, 2008) assesses parent ratings of 
their adolescents’ executive functioning. Parents will respond to 24 items (e.g., “Has difficulty 
thinking ahead or learning from experience.”) using a 5-item Likert scale (1 = Definitely not 
true; 5 = Definitely true). There are four subscales: Working Memory, Planning, Inhibition, and 
Regulation.  
 
Spence Children’s Anxiety Scale: Parent Report, Brief Version (SCAS-P-8; Reardon, Spence, 
Hesse, Shakir, & Creswell, 2018) assesses parent report of their adolescents’ anxiety. Parents 
will respond to 8 items (e.g., “My child worries about things.”) using a 4-point Likert scale 
(1=Never, 4 = Always).  
 
The PROMIS Pediatric Global Health Measure (PGH-7 Parent Proxy Report; Forrest et al., 
2014) assesses parent reports of their adolescents’ overall health and wellbeing across 7 items. 
Parents will respond to 4 items (e.g., In general, would you say your child’s quality of life is…) 
using a 5-point Likert scale (5 = Excellent, 1 = Poor); 1 item (e.g., How often does your child 
feel really sad) using a 5-point Likert scale (5 = Never; 1 = Always); and 2 items (e.g., How 
often does your child have fun with friends?) using a 5-point Likert scale (5 = Always; 1 = 
Never). 
 
Implementation: 
 
Dosage. iRT’s LMS will record the number of program lessons completed by adolescents and 
amount of time that adolescents spend in the program.  
 
Engagement. iRT’s LMS will record the number of Likert-type rating scale questions that 
adolescents respond to as part of the lesson activities in the Aware Program.  

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Consumer Satisfaction: 
 
Consumer Satisfaction Questionnaire for Adolescents (CSQ-A) will assess adolescents’ 
satisfaction with the Aware Program in terms of: (1) content (e.g., I think the information 
provided in this program is important for teens like me.); (2) format (e.g., The games and 
activities in the Aware program were fun.); and (3) usability (e.g., I found it easy to go through 
the program.).  Overall quality will also be assessed (e.g., I would recommend the Aware 
program to a friend or another teen.).  Participants will rate each item on a 5-point Likert 
scale. Participants will also be asked an open-ended question for improving the program (e.g., Is 
there anything you think we could do to make the Aware Program better?).  
 
Consumer Satisfaction Questionnaire for Parents (CSQ-P) will assess parents’ satisfaction with 
the Aware Program. The questions will include (1) content (e.g., The information on the My 
Teen’s Course Progress page was helpful to me.), (2) format (e.g., The design of the My Teen’s 
Course Progress page was pleasant.), and (3) usability (e.g., It took a long time for the pages to 
load in the Parent Dashboard). Overall quality will also be assessed (e.g., I would recommend 
the Aware Program to another parent of a teen with 22q11DS). Participants will rate each item 
on a 5-point Likert scale. Parents will also be able to share open-ended feedback about their 
experience using the Aware program (e.g., What did you like best about the text messaging 
system?).  
 
Statistical Analysis Plan 
 
Data will be analyzed using SAS 9.4.  
 
Preliminary analyses. Psychometric and other descriptive analyses will be conducted of 
the reliability, validity, and distributions of key measures. Summary scores will be created and 
distributions, internal consistencies, and intercorrelations of these scores will be reviewed as 
indices of reliability and validity. In addition, the impact of random assignment on producing 
essentially equivalent groups for the intervention and control conditions will be analyzed in a 
series of t-test and chi-square models estimated for each demographic variable at outcome 
variable at baseline. Missing data at each time point will also be examined using the appropriate 
imputation method and estimates and standard errors adjusted for imputations, if warranted. 
 
Main Analyses.  Multiple regression analyses will be used to investigate differences in 
outcomes (i.e., coping strategies, emotion regulation, global health, executive functioning, and 
anxiety) using condition (intervention; wait-list control) as the independent variable of interest. 
A series of multiple regressions will be used to examine if using the Aware Program impacts the 
post-test coping, emotion regulatory abilities, global health, executive functioning, and anxiety 
of adolescent participants. Pre-test scores for each outcome will be included as predictor 
variables; thus, outcome variable means will be reported as adjusted post-test scores. 
Demographic variables found to be non-equivalent between groups will be included as covariates 
in these models. The effect sizes will be calculated by dividing the appropriate contrast 
parameter by the sample standard deviation of the outcome. Analyses will be intent-to-treat, so 

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that participants who do not adhere to the protocol will be still included in the analysis in their 
assigned condition.  
 
Fidelity and Consumer Satisfaction. The process data recorded for the intervention 
group by the LMS (e.g., lessons completed, time spent using the program, number of activities 
completed) will be examined to determine dosage and engagement. In addition, consumer 
satisfaction responses will be examined including mean scale scores on the CSQ (e.g., format, 
usability). Responses to qualitative items will be summarized, and similar patterns of responses 
will be grouped by content.