Software Treatment for Actively Reducing Severity of ADHD

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of videogame-like digital therapies on attentional functioning and symptoms in children diagnosed with ADHD.

Detailed Description
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The study will be a randomized, parallel group, controlled trial of two videogame-like (iPad-based) digital therapies. The study will consist of 3 primary phases: Screening, Washout/Baseline, and Treatment. During the Screening Phase (Day -28 to Day -7), participants will undergo screening to evaluate eligibility for the study. Screening may take place up to 28 days before the Baseline Visit (Day 0). For those children currently on medication for ADHD the Washout period will begin 7 days prior to Baseline where treatment will be discontinued. On Day 0, the Baseline visit will occur wherein additional eligibility criteria will be established. The Treatment Phase (Day 1 to Day 27) will involve using the digital therapy at home for each participant followed by an In-Clinic assessment on Day 28 to assess key outcomes. Compliance with treatment/use requirements will be monitored remotely during this phase.

Official Title
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A Randomized, Controlled, Parallel-group, Intervention Study to Assess At-home, Game-based Digital Therapy for Treating Pediatric Participants Ages 8 to 12 Years Old With Attention Deficit Hyperactivity Disorder (ADHD)

Conditions
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Attention Deficit Disorder With Hyperactivity

Intervention / Treatment
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* Device: AKL-T01
* Device: AKL-T09


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed ADHD diagnosis, any presentation, at Screening based on the Diagnostic and Statistical Manual of Mental Health-Fifth Edition criteria and established via the MINI-International Neuropsychiatric Interview for Children and Adolescents administered by a trained clinician Screening/Baseline score on the clinician-rated ADHD-RS-IV score >= 28 Screening/Baseline score on the TOVA 8 API <= -1.8 Not undergoing pharmacological treatment with methylphenidate or amphetamine-based products at time of Screening; or, if undergoing pharmacological treatment, must be willing and appropriate (i.e. not optimally treated in the investigator's judgment) to wash out of current regimen Ability to follow written and verbal instructions (English), as assessed by the PI Estimated Intelligence Quotient score >= 80 as assessed by the Kaufmann Brief Intelligence Test, Second Edition (KBIT-II) Ability to comply with all the testing and requirements. Exclusion Criteria: Current, controlled (requiring a restricted medication) or uncontrolled, comorbid psychiatric diagnosis, based on MINI-KID and subsequent clinical interviewing, with significant symptoms including but not limited to post-traumatic stress disorder, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder, conduct disorder, or other symptomatic manifestations that in the opinion of the Investigator that may confound study data/assessments. Participants with clinical history of learning disorders will be allowed to participate, provided the disorder does not impact their ability to participate in the trial based on PI judgment Participants who are currently treated with a non-stimulant medication for ADHD (i.e., atomoxetine, clonidine clonidine, guanfacine) Initiation within the last 4 weeks of behavioral therapy. Participants who have been in behavior therapy consistently for more than 4 weeks may participate provided their routine is unchanged during the course of the study. Participants planning on changing or initiating behavior therapy during the course of the study will be excluded Participant is currently considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or has a prior history of, or is currently demonstrating active suicidal ideation or self-injurious behavior as measured by Columbia Suicide Severity Rating Scale at screening Motor condition (e.g., physical deformity of the hands/arms; prostheses) that prevents game playing as reported by the parent or observed by the investigator Recent history (within the past 6 months) of suspected substance abuse or dependence History of seizures (exclusive of febrile seizures), or significant motor or vocal tics, including but not limited to Tourette's Disorder Has participated in a clinical trial within 90 days prior to screening Diagnosis of or parent-reported color blindness (Confirmed in-clinic via ICBT) Uncorrected visual acuity (Confirmed in-clinic via ability of subject to play the intervention) Regular use of psychoactive drugs (other than stimulant) that in the opinion of the Investigator may confound study data/assessments Any other medical condition that in the opinion of the investigator may confound study data/assessments Has a sibling also enrolled/currently participating in the same study Has previously participated in a study of Akili's EVO videogame-like digital therapy

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Minimum number of subjects = 300, Anticipated number of subjects = 330, Maximum number of subjects = 1,000
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AKL-T01 (EVO Multi)<br>AKL-T01, or EVO Multi, is a digital intervention that requires the subject to navigate a character through a game-like space, while collecting objects, in a fixed period of time. | Device: AKL-T01<br>* Videogame-like digital therapy<br>* Other names: EVO Multi;|
| Active Comparator: AKL-T09 (EVO Words)<br>AKL-T09, or EVO Words, is a digital intervention that requires the subject to spell as many words as possible, by connecting letters in a game-like grid, in a fixed period of time. | Device: AKL-T09<br>* Videogame-like digital therapy<br>* Other names: EVO Words;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test of Variables of Attention-Attention Performance Index (Change From Baseline to Posttreatment) | TOVA API is a comparison of the subject's scores based on selected measures that persons with an independent diagnosis of ADHD frequently demonstrated. The API is calculated from variability, response time, and d' (D Prime) using the following formula: API = Response Time Z score (Half 1) + d' Z score (Half 2) + Variability Z score (Total) + 1.80 where Response Time is the average time it takes to respond correctly to a target, d' score is a response discriminability score reflecting the ratio of hits to false alarms, and Variability is a measure of consistency of speed of responding based on the standard deviation of the mean correct response times. API tells how similar the score is to the ADHD profile. A score of less than 0 indicates that the subject had similar performance to a normative ADHD population. A lower score indicates a more severe ADHD profile. The calculation for difference in TOVA API was API at Day 28 minus API at Day 0 of this study. | Day 0 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADHD-RS Total (Change From Baseline to Posttreatment) | The ADHD-RS-IV is an 18-item, clinician-administered questionnaire for which a parent respondent rates the frequency of occurrence of ADHD symptoms and behaviors as defined by criteria outlined for ADHD in the DSM-IV. Each item is scored on a 4-point scale ranging from 0 (rarely or never) to 3 (very often) with total scores ranging from 0-54. A higher score indicates more severe ADHD symptoms and behaviors. A negative change in total score indicates improvement from Day 0 to Day 28. | Day 0 to Day 28 | 
| ADHD-RS Inattentive Subscale (Change From Baseline to Posttreatment) | The ADHD-RS-IV is an 18-item, clinician-administered questionnaire for which a parent respondent rates the frequency of occurrence of ADHD symptoms and behaviors as defined by criteria outlined for ADHD in the DSM-IV. Each item is scored on a 4-point scale ranging from 0 (rarely or never) to 3 (very often) with total scores ranging from 0-54. A higher score indicates more severe ADHD symptoms and behaviors. The 18 items are grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17). Each subscale produces a sub-scale score ranging from 0-27. A higher subscale score indicates more severe ADHD symptoms and behaviors. A negative change indicated improvement on the subscale from Day 0 to Day 28. | Day 0 to Day 28 | 
| ADHD-RS Hyperactivity Subscale (Change From Baseline to Posttreatment) | The ADHD-RS-IV is an 18-item, clinician-administered questionnaire for which a parent respondent rates the frequency of occurrence of ADHD symptoms and behaviors as defined by criteria outlined for ADHD in the DSM-IV. Each item is scored on a 4-point scale ranging from 0 (rarely or never) to 3 (very often) with total scores ranging from 0-54. A higher score indicates more severe ADHD symptoms and behaviors. The 18 items are grouped into 2 subscales: hyperactivity/impulsivity (even numbered items 2-18) and inattentiveness (odd numbered items 1-17). Each subscale produces a sub-scale score ranging from 0-27. A higher subscale score indicates more severe ADHD symptoms and behaviors. A negative change indicated improvement on the subscale from Day 0 to Day 28. | Study Day 0 to Study Day 28 | 
| BRIEF Working Memory Percentile (Change From Baseline to Posttreatment) | The Behavior Rating Inventory of Executive Function (BRIEF) is a parent-rated form that assesses everyday behavior associated with specific domains of the executive functions of their child. The BRIEF working memory metacognition subscale measures the participants ability to hold information when completing a task in a sequential manner. A negative change in percentile indicated an improvement on the subscale. | Day 0 to Day 28 | 
| BRIEF Inhibit Percentile (Change From Baseline to Posttreatment) | The Behavior Rating Inventory of Executive Function (BRIEF) is a parent-rated form that assesses everyday behavior associated with specific domains of the executive functions of their child. The BRIEF Inhibit subscale measures the participant's ability to control impulses and to stop engaging in a behavior. A negative change in percentile indicated an improvement on the subscale. | Day 0 to Day 28 | 
| Impairment Rating Scale, Overall Impairment (Change From Baseline to Posttreatment) | The Impairment Rating Scale (IRS) is a parent-rated scale that assesses individualized areas of impairment for a child participant and asks parents to make a rating of how significantly these problems impact functioning across a range of domains (social, family, school, self-esteem). Parents describe the primary areas of difficulty for each child and then provide a rating (via a Visual Analog Scale) of how much the difficulties affect the different areas of functioning ranging from (1) no problem; definitely does not need treatment or special services to (7) extreme problem; definitely needs treatment or special services. The total IRS is 8 items, the 8th rating overall impairment. A negative change indicated a decrease in overall impairment. | Day 0 to Day 28 | 
| CGI-I (at Posttreatment) | The Clinical Global Impression Scale - Improvement (CGI-I) is a clinician's comparison of the participant's overall clinical condition at follow up to the overall clinical condition at baseline. The CGI-S is a 7-point scale where 1 = Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Minimally worse, 6=Much worse, and 7=Very much worse. A score of 1, 2, or 3 would indicate overall improvement of ADHD severity. | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD