Cognitive Rehabilitation (Mega Team) and Its Effects on Emotional and Behavioral Regulation in ADHD, ASD, and CHD

ADHD Clinical Trial

Official title:

Cognitive Rehabilitation (Mega Team) and Its Effects on Emotional and Behavioral Regulation in ADHD, ASD, and CHD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03502239
• Other study ID #: 1000057380
• Status: Recruiting
• Phase: N/A
• Start date: May 26, 2018
• Est. completion date: December 2023

Study information

• Verified date: May 2021
• Source: The Hospital for Sick Children
• Contact: Taha Arshad, Hon.B.Sc
• Phone: 416-813-8210
• Email: taha.arshad[@]sickkids.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Children with disorders that impact neurodevelopment often have difficulties with executive functions and regulating emotions. Cognitive-based video game training has been shown to improve outcomes, however, this training has been expensive, has required professional supervision, and has been investigated only within a narrow group of children. The Mega Team study will test the effects of a highly engaging, take-home video game-based intervention designed to improve executive functioning in children with various brain-based developmental disorders.

Description:

The target population for this study will be children between the ages of 6-12 with a diagnosis of ADHD, ASD or CHD. Potential subjects for this study will be recruited from the clinical teams within SickKids and partnering institutions (e.g., CAMH and Holland Bloorview). Participants will be identified by a psychiatrist, psychologist or specialist physician as meeting diagnostic criteria for one of the three disorders; 1) ADHD, 2) ASD, 3) CHD. Families of children who have expressed interested in this study will be contacted by research staff to discuss the study in more detail and will coordinate the logistics of an initial consent and enrollment appointment. Parent(s)/guardian(s) of participants will be required to consent and children will be required to assent to take in this study.

This protocol is divided into 3 studies: sub-study 1 (ADHD), sub-study 2 (ASD) and sub-study 3 (CHD) each consisting of a pre-post treatment design with 6 month follow-up. Each sub-study includes an active treatment and wait -list arm. Please see study visit schedule (pg. 11) for time-line of events and measures by participant at each time point. Participants will be tested at SickKids at pre-treatment, post-treatment and follow-up. Participants will train at home with weekly calls from research staff. Assessors at all clinic visits will be blind to treatment status. All pre, post and following-up clinic assessments will be conducted off stimulant medication with a washout period of 48 hours.

Stratification: Participants may be taking medications at the time of the study (stimulants and non-stimulants including SSRI or antipsychotic medications). Families will be asked to be stabilized on their current dose of medication for at least for a month before commencing the study and to maintain the same medication and dosage during the 5 week study. If a change in the type of medication or dosage takes place during the study it will be recorded. Due to the established impact of stimulant medications on EF 20 21 this class of medication will be used as part of the randomization process to attain equal proportions of participants using stimulant medications in the Mega Team and TAU groups. As some medication use is anticipated in all disorder groups the same randomization approach will be used in all three studies.

Sample Size: The sample size for sub-study 1 (ADHD) will be 220 participants with 110 randomized into each group from initial estimated recruitment pool of 250. The sample size will provide 80% power to declare statistical significance if the true difference between treatment groups is 0.43 standard deviations or greater, using a two-sided, 5% level test of hypothesis, Bonferroni corrected for three comparisons. A pilot study of Mega Team is currently underway (Dr. Crosbie PI, a registered clinical trial) and results from that pilot will provide final estimates of the standard deviations before commencement of the current study. The planned sample for each of sub-study 2 (ASD) and sub-study 3 (CHD) will be 120 (60 per arm) given the novelty of investigating cognitive rehabilitation targeting EFs in these populations. Information from sub-study 1, which will happen first, and the results from the Mega Team pilot study, will allow adjustment in sample size of sub-study 2 and sub-study 3. All aspects of enrollment, randomization, and attrition will be monitored and documents using CONSORT flow diagram22.

Randomization: Participants within each sub-study who have consented/ assented to the study and meet all inclusion criterion will be randomized to either Mega Team or TAU waitlist stratified by medication status (yes or no)) using random block sizes. Randomization will be carried out using RedCAP23.

Blinding: Assessors at all clinic visits will be blind to treatment status. Participants and parents will be asked not to make mention of their treatment status during visits. They will be reminded of this regularly. Assessors will indicate their blinded status at the end of all visits. Parents and children will be asked not to inform teachers of the treatment status. At the time of questionnaire completion, teachers will be asked if they are aware of the treatment status of the child.

Intervention Conditions:

Mega Team Training Sessions: Mega Team is highly engaging video game based cognitive intervention that trains multiple executive functions: response inhibition, verbal working memory and visual working memory in the context of a single game with increasing difficulty based on the individual performance. Children in the treatment group will train at home on their own tablet or on a study tablet provided to the family (if needed). They will be instructed to practice Mega Team for 15 minutes a day, approximately 5 days a week for a targeted minimum of 21 sessions and a maximum of 25 sessions. The minimum value of 21 sessions has been selected based on findings of prior research. Majority of studies using other models of intervention have been able to capture significant training-induced improvements after 21 sessions 24-26. The maximum training of 25 sessions has been set to control for variability within and between our groups. Performance on Mega Team will automatically upload to a secure portal hosted by eHave for monitoring of enrolment, adherence and for data analyses. Scoring algorithms will track how often and how long the participants trained on Mega Team as well as their performance. Weekly calls from research staff will provide motivation and address barriers to game play.

TAU waiting list Control: Children in the control group will not be provided with any overt intervention but continue with treatment recommendations as provided by their clinical care team. They will be asked to complete a video game usage log weekly to record the type and duration of their regular video game playing, and will receive weekly calls from research staff, as will participants assigned to Mega Team. Participants on in the TAU group will be given access to the game at the completion of the 6 month follow-up visit.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 440
• Est. completion date: December 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 12 Years

Eligibility

Inclusion Criteria:

• Sub-Study 1 Inclusion Criteria

1. Must be 6-12 years of age

2. Have IQ above 70 as estimated by two subtests of the Wechsler Abbreviated Scale of intelligence, Second Edition (WASI II) or equivalent.

3. Diagnosed with ADHD based upon DSM 5 criteria by a referring clinician confirmed by semi structured interview with the parents using PICS, including information from parent and teacher ratings of an established measure of ADHD symptoms.

4. Does not have a diagnosis of ASD or CHD [in this case, individuals can be enrolled into Study 2 (ASD) or Study 3 (CHD)].

5. Have reliable access to the internet

• Sub-Study 2 inclusion criteria

1. Must be 6-12 years of age

2. Have IQ above 70 as estimated by two subtests of the Wechsler Abbreviated Scale of intelligence, Second Edition (WASI II) or equivalent

3. Meets clinical diagnosis of ASD by referral services (Holland Bloorview, CAMH) supported by ADOS.

4. Have reliable access to the internet

• Sub-Study 3 inclusion criteria

1. Must be 6-12 years of age

2. Have IQ above 70 as estimated by two subtests of the Wechsler Abbreviated Scale of intelligence, Second Edition (WASI II) or equivalent

3. Must have a diagnosis of Transposition of the Great Arteries (TGA) or Hypoplastic left heart syndrome

4. Must have received cardiac surgery before 6 weeks of age.

5. Have reliable access to the internet

Exclusion Criteria:

• Sub-Study 1 Exclusion Criteria

1. Younger than 6 years or older than 12

2. IQ below 70 as estimated by two subtests of the Wechsler Abbreviated Scale of intelligence, Second Edition (WASI II) or equivalent

3. Does not meet consensus diagnosis of DSM 5 criteria for ADHD based on a semi structured interview with the parents using PICS-6, including information from parent and teacher ratings of an established measure of ADHD symptoms.

4. Has a diagnosis of ASD or CHD [in this case, individuals can be enrolled into Study 2 (ASD) or Study 3 (CHD)].

• Sub-Study 2 exclusion criteria

1. Younger than 6 years or older than 12

2. IQ below 70 as estimated by two subtests of the Wechsler Abbreviated Scale of intelligence, Second Edition (WASI II) or equivalent

3. Does not meet confirmed diagnosis of ASD based on ADOS

• Sub-Study 3 exclusion criteria

1. Younger than 6 years or older than 12

2. IQ below 70 as estimated by two subtests of the Wechsler Abbreviated Scale of intelligence, Second Edition (WASI II) or equivalent

3. Does not have a diagnosis of Transposition of the Great Arteries (TGA) or Hypoplastic left heart syndrome

4. Did not receive cardiac surgery before 6 weeks of age.

Related Conditions & MeSH terms

• ADHD
• ASD
• CHD - Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases

Intervention

Other:
• Mega Team - video game
Subjects randomly assigned to the treatment group will be instructed to practice Mega Team for 15 minutes a day, 5 days a week for a minimum of 21 days and a maximum of 25 days.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (4)

Lead Sponsor	Collaborator
The Hospital for Sick Children	Child-Bright Network, Ehave, The Governors of the University of Alberta

Country where clinical trial is conducted

Canada, 

References & Publications (30)

Alloway, T. Can interactive working memory training improving learning? J. Interact. Learn. Res. 23, 197-207 (2012)

Baron IS. Behavior rating inventory of executive function. Child Neuropsychol. 2000 Sep;6(3):235-8. Erratum in: Child Neuropsychol. 2016;22(6):761. — View Citation

Beck SJ, Hanson CA, Puffenberger SS, Benninger KL, Benninger WB. A controlled trial of working memory training for children and adolescents with ADHD. J Clin Child Adolesc Psychol. 2010;39(6):825-36. doi: 10.1080/15374416.2010.517162. — View Citation

Bedard AC, Ickowicz A, Logan GD, Hogg-Johnson S, Schachar R, Tannock R. Selective inhibition in children with attention-deficit hyperactivity disorder off and on stimulant medication. J Abnorm Child Psychol. 2003 Jun;31(3):315-27. — View Citation

Bedard AC, Martinussen R, Ickowicz A, Tannock R. Methylphenidate improves visual-spatial memory in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2004 Mar;43(3):260-8. — View Citation

Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P; CONSORT Group. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med. 2008 Feb 19;148(4):295-309. — View Citation

Bussing R, Fernandez M, Harwood M, Wei Hou, Garvan CW, Eyberg SM, Swanson JM. Parent and teacher SNAP-IV ratings of attention deficit hyperactivity disorder symptoms: psychometric properties and normative ratings from a school district sample. Assessment. 2008 Sep;15(3):317-28. doi: 10.1177/1073191107313888. Epub 2008 Feb 29. — View Citation

Calderon J, Bellinger DC. Executive function deficits in congenital heart disease: why is intervention important? Cardiol Young. 2015 Oct;25(7):1238-46. doi: 10.1017/S1047951115001134. Epub 2015 Jun 17. Review. — View Citation

Chein JM, Morrison AB. Expanding the mind's workspace: training and transfer effects with a complex working memory span task. Psychon Bull Rev. 2010 Apr;17(2):193-9. doi: 10.3758/PBR.17.2.193. — View Citation

Cortese S, Ferrin M, Brandeis D, Buitelaar J, Daley D, Dittmann RW, Holtmann M, Santosh P, Stevenson J, Stringaris A, Zuddas A, Sonuga-Barke EJ; European ADHD Guidelines Group (EAGG). Cognitive training for attention-deficit/hyperactivity disorder: meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials. J Am Acad Child Adolesc Psychiatry. 2015 Mar;54(3):164-74. doi: 10.1016/j.jaac.2014.12.010. Epub 2014 Dec 29. Review. Erratum in: J Am Acad Child Adolesc Psychiatry. 2015 May;54(5):433. — View Citation

Craig F, Margari F, Legrottaglie AR, Palumbi R, de Giambattista C, Margari L. A review of executive function deficits in autism spectrum disorder and attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat. 2016 May 12;12:1191-202. doi: 10.2147/NDT.S104620. eCollection 2016. Review. — View Citation

Dahlin E, Nyberg L, Bäckman L, Neely AS. Plasticity of executive functioning in young and older adults: immediate training gains, transfer, and long-term maintenance. Psychol Aging. 2008 Dec;23(4):720-30. doi: 10.1037/a0014296. — View Citation

Dahlin, K. I. E. Effects of working memory training on reading in children with special needs. Read. Writ. 24, 479-491 (2011)

Delis, D., Kaplan, E. & Kramer, J. Delis-Kaplan executive function system (D-KEFS). Can. J. Sch. Psychol. 20, 117-128 (2001)

Diamond A. Executive functions. Annu Rev Psychol. 2013;64:135-68. doi: 10.1146/annurev-psych-113011-143750. Epub 2012 Sep 27. Review. — View Citation

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. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30. — View Citation

Holmes J, Gathercole SE, Dunning DL. Adaptive training leads to sustained enhancement of poor working memory in children. Dev Sci. 2009 Jul;12(4):F9-15. doi: 10.1111/j.1467-7687.2009.00848.x. — View Citation

Jaeggi SM, Buschkuehl M, Jonides J, Perrig WJ. Improving fluid intelligence with training on working memory. Proc Natl Acad Sci U S A. 2008 May 13;105(19):6829-33. doi: 10.1073/pnas.0801268105. Epub 2008 Apr 28. — View Citation

Johnstone SJ, Roodenrys S, Blackman R, Johnston E, Loveday K, Mantz S, Barratt MF. Neurocognitive training for children with and without AD/HD. Atten Defic Hyperact Disord. 2012 Mar;4(1):11-23. doi: 10.1007/s12402-011-0069-8. Epub 2011 Dec 20. — View Citation

Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997 Jul;36(7):980-8. — View Citation

Lawson RA, Papadakis AA, Higginson CI, Barnett JE, Wills MC, Strang JF, Wallace GL, Kenworthy L. Everyday executive function impairments predict comorbid psychopathology in autism spectrum and attention deficit hyperactivity disorders. Neuropsychology. 2015 May;29(3):445-53. doi: 10.1037/neu0000145. Epub 2014 Oct 13. — View Citation

Logan, G. D., Schachar, R. J. & Tannock, R. Impulsivity and Inhibitory Control. Psychol. Sci. 8, 60-64 (1997)

McAuley T, Crosbie J, Charach A, Schachar R. The persistence of cognitive deficits in remitted and unremitted ADHD: a case for the state-independence of response inhibition. J Child Psychol Psychiatry. 2014 Mar;55(3):292-300. doi: 10.1111/jcpp.12160. Epub 2013 Nov 22. — View Citation

Morris MC, Evans LD, Rao U, Garber J. Executive function moderates the relation between coping and depressive symptoms. Anxiety Stress Coping. 2015;28(1):31-49. doi: 10.1080/10615806.2014.925545. Epub 2014 Jun 17. — View Citation

Shalev L, Tsal Y, Mevorach C. Computerized progressive attentional training (CPAT) program: effective direct intervention for children with ADHD. Child Neuropsychol. 2007 Jul;13(4):382-8. — View Citation

Van der Molen MJ, Van Luit JE, Van der Molen MW, Jongmans MJ. Everyday memory and working memory in adolescents with mild intellectual disability. Am J Intellect Dev Disabil. 2010 May;115(3):207-17. doi: 10.1352/1944-7558-115.3.207. — View Citation

Vinogradov S, Fisher M, de Villers-Sidani E. Cognitive training for impaired neural systems in neuropsychiatric illness. Neuropsychopharmacology. 2012 Jan;37(1):43-76. doi: 10.1038/npp.2011.251. Epub 2011 Nov 2. Review. — View Citation

Wechsler, D. WASI -II: Wechsler abbreviated scale of intelligence - second edition. J. Psychoeduc. Assess. 31, 337-41 (2013)

Willcutt EG, Doyle AE, Nigg JT, Faraone SV, Pennington BF. Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review. Biol Psychiatry. 2005 Jun 1;57(11):1336-46. Review. — View Citation

Woodcock, R. W., McGrew, K. S. & Mather, N. Woodcock-Johnson III Tests of Achievement. Test 2001, 1-9 (2001)

* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Response Inhibition	Inhibitory control will be measured using the Stop Signal Task (SST). The SST measures the ability to cancel an already initiated motor response. The primary outcome measure will be the participants' average stop signal reaction time (SSRT).	Baseline, Post-training study visit #1 (4-5 weeks after baseline), Post-training study visit #2 (6 months after baseline)
Primary	Change in Working Memory	Verbal and Spatial N-back (1, 2 conditions) will be used to assess central executive working memory. The N-Back task requires on-line monitoring, updating, and manipulation of information and measures key processes within working memory. In the N-Back task, the participant is required to monitor a series of stimuli and to respond whenever a stimulus is presented that is the same as the one presented n trials previously, where n is a pre-specified integer, usually 0, 1, or 2. The current study will use letters (verbal) and spatial location (spatial) paradigms. Visual and spatial working memory span will be assessed using the Spatial Span subtest and the Digit Span item from the WISC-IV Integrated. The primary outcome measure will be the overall score.	Baseline, Post-training study visit #1 (4-5 weeks after baseline), Post-training study visit #2 (6 months after baseline)
Secondary	Planning and Organization	The Tower Test from the Delis-Kaplan Executive Function System (D-KEFS;28 is a test of planning and problem solving abilities. Participants are asked to construct towers of discs on a set of pegs corresponding to a model. Raw scores reflect the participant's ability to use the fewest possible moves to achieve the tower depicted in the model.	Baseline, Post-training study visit #1 (4-5 weeks after baseline), Post-training study visit #2 (6 months after baseline)
Secondary	Everyday functioning and impairment	Parent and teacher rating of behaviours and impairments associated with executive functions will be assessed using The Behavior Rating Inventory of Executive Function (BRIEF;29). This is a 86 item questionnaires with solid psychometric properties (ref) with correlations with other measures of emotional and behavioral functioning29.	Baseline, Post-training study visit #1 (4-5 weeks after baseline), Post-training study visit #2 (6 months after baseline)
Secondary	Inattentive and Hyperactivity Behaviour rated by parent and teacher	Items associated with inattentiveness and hyperactivity from the SNAP IV will be used to estimate behavioural symptoms associated with ADHD. The SNAP-IV (SNAP-IV; Swanson IV, 2003) is an 18-item scale that includes the DSM-IV criteria for ADHD with items 1-9 representing the inattentive subset of symptoms and items 10-18 representing the Hyperactivity/Impulsivity subset.	Baseline, Post-training study visit #1 (4-5 weeks after baseline), Post-training study visit #2 (6 months after baseline)
Secondary	Academic accuracy and efficiency	Academic efficiency and accuracy will be assessed using the fluency measures from the Woodcock Johnson III30 test of achievement. The fluency tasks measure the accuracy of completing academic tasks within a time limit. Reading, math and writing fluency subtests will be included.	Baseline, Post-training study visit #1 (4-5 weeks after baseline), Post-training study visit #2 (6 months after baseline)