Attention Deficit Disorder With Hyperactivity
Conditions
Keywords
ADHD
Brief summary
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
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.
Interventions
DEVICEAKL-T01
Videogame-like digital therapy
DEVICEAKL-T09
Videogame-like digital therapy
Sponsors
Akili Interactive Labs, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Minimum number of subjects = 300, Anticipated number of subjects = 330, Maximum number of subjects = 1,000
Eligibility
Sex/Gender
ALL
Age
8 Years to 12 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Test of Variables of Attention-Attention Performance Index (Change From Baseline to Posttreatment) | Day 0 to Day 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ADHD-RS Inattentive Subscale (Change From Baseline to Posttreatment) | Day 0 to Day 28 | 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. |
| ADHD-RS Hyperactivity Subscale (Change From Baseline to Posttreatment) | Study Day 0 to Study Day 28 | 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. |
| BRIEF Working Memory Percentile (Change From Baseline to Posttreatment) | Day 0 to Day 28 | 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. |
| ADHD-RS Total (Change From Baseline to Posttreatment) | Day 0 to Day 28 | 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. |
| Impairment Rating Scale, Overall Impairment (Change From Baseline to Posttreatment) | Day 0 to Day 28 | 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. |
| CGI-I (at Posttreatment) | Day 28 | 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. |
| BRIEF Inhibit Percentile (Change From Baseline to Posttreatment) | Day 0 to Day 28 | 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. |
Countries
United States
Participant flow
Pre-assignment details
Participants who met full criteria for ADHD at Screening and who the PI believed were not optimally treated with current medication were eligible to washout their medication regimen. For those electing to washout, treatment was discontinued between 7 and 3 days prior to their scheduled Baseline Visit.
Participants by arm
| Arm | Count |
|---|---|
| AKL-T01 (EVO Multi) 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.
AKL-T01: Videogame-like digital therapy | 180 |
| AKL-T09 (EVO Words) 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.
AKL-T09: Videogame-like digital therapy | 168 |
| Total | 348 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Parent/Guardian | 1 | 2 |
Baseline characteristics
| Characteristic | AKL-T09 (EVO Words) | AKL-T01 (EVO Multi) | Total |
|---|---|---|---|
| Age, Continuous | 9.601 years STANDARD_DEVIATION 1.341 | 9.711 years STANDARD_DEVIATION 1.322 | 9.658 years STANDARD_DEVIATION 1.331 |
| Race/Ethnicity, Customized Black or African American | 26 Participants | 25 Participants | 51 Participants |
| Race/Ethnicity, Customized Other | 23 Participants | 22 Participants | 45 Participants |
| Race/Ethnicity, Customized White | 119 Participants | 133 Participants | 252 Participants |
| Region of Enrollment United States | 168 participants | 180 participants | 348 participants |
| Sex: Female, Male Female | 45 Participants | 55 Participants | 100 Participants |
| Sex: Female, Male Male | 123 Participants | 125 Participants | 248 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 180 | 0 / 168 |
| other Total, other adverse events | 12 / 180 | 3 / 168 |
| serious Total, serious adverse events | 0 / 180 | 0 / 168 |
Outcome results
Primary
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.
Time frame: Day 0 to Day 28
Population: Intent to Treat Population - all randomized participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T01 (EVO Multi) | Test of Variables of Attention-Attention Performance Index (Change From Baseline to Posttreatment) | 0.93 z-score | Standard Deviation 3.2 |
| AKL-T09 (EVO Words) | Test of Variables of Attention-Attention Performance Index (Change From Baseline to Posttreatment) | 0.03 z-score | Standard Deviation 3.2 |
Secondary
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.
Time frame: Study Day 0 to Study Day 28
Population: Intent to Treat Population - all randomized participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T01 (EVO Multi) | ADHD-RS Hyperactivity Subscale (Change From Baseline to Posttreatment) | -2.6 score on a scale | Standard Deviation 4.2 |
| AKL-T09 (EVO Words) | ADHD-RS Hyperactivity Subscale (Change From Baseline to Posttreatment) | -2.5 score on a scale | Standard Deviation 4.5 |
Secondary
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.
Time frame: Day 0 to Day 28
Population: Participants in the ITT (all randomized participants) from whom both Day 0 and Day 28 data was able to be collected in full. For the ADHD-RS, this population included all participants for whom all 9 items of the sub-scale were completed. In the AKL-T01 arm, two participants were missing a response for at least one item of the sub-scale.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T01 (EVO Multi) | ADHD-RS Inattentive Subscale (Change From Baseline to Posttreatment) | -3.6 score on a scale | Standard Deviation 4.8 |
| AKL-T09 (EVO Words) | ADHD-RS Inattentive Subscale (Change From Baseline to Posttreatment) | -3.2 score on a scale | Standard Deviation 5 |
Secondary
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.
Time frame: Day 0 to Day 28
Population: Participants in the ITT (all randomized participants) from whom both Day 0 and Day 28 data was able to be collected in full. For the ADHD-RS, this population included all participants for whom all 18 items of the rating scale were completed. In the AKL-T01 arm, two participants were missing a response for at least one item of the ADHD-RS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T01 (EVO Multi) | ADHD-RS Total (Change From Baseline to Posttreatment) | -6.2 score on a scale | Standard Deviation 7.6 |
| AKL-T09 (EVO Words) | ADHD-RS Total (Change From Baseline to Posttreatment) | -5.7 score on a scale | Standard Deviation 8.2 |
Secondary
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.
Time frame: Day 0 to Day 28
Population: Participants in the ITT from whom both Day 0 and Day 28 data was able to be collected in full. For BRIEF Inhibit this includes all participants for whom all items of the sub-scale were completed. In both the AKL-T01 and AKL-T09 arms 9 participants were missing a response for at least one item (18 total participants were missing responses to items).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T01 (EVO Multi) | BRIEF Inhibit Percentile (Change From Baseline to Posttreatment) | -2.8 percentile | Standard Deviation 13.3 |
| AKL-T09 (EVO Words) | BRIEF Inhibit Percentile (Change From Baseline to Posttreatment) | -3.5 percentile | Standard Deviation 9.2 |
Secondary
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.
Time frame: Day 0 to Day 28
Population: Participants in the ITT from whom both Day 0 and Day 28 data was able to be collected in full. For the BRIEF WM, this includes all participants for whom all items of the sub-scale were completed. In both the AKL-T01 and AKL-T09 arms 9 participants were missing a response for at least one item (18 total participants were missing responses to items).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T01 (EVO Multi) | BRIEF Working Memory Percentile (Change From Baseline to Posttreatment) | -3.1 percentile | Standard Deviation 8 |
| AKL-T09 (EVO Words) | BRIEF Working Memory Percentile (Change From Baseline to Posttreatment) | -3.3 percentile | Standard Deviation 9.4 |
Secondary
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.
Time frame: Day 28
Population: Intent to Treat Population - all randomized participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T01 (EVO Multi) | CGI-I (at Posttreatment) | 3.4 score on a scale | Standard Deviation 0.9 |
| AKL-T09 (EVO Words) | CGI-I (at Posttreatment) | 3.4 score on a scale | Standard Deviation 0.9 |
Secondary
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.
Time frame: Day 0 to Day 28
Population: Participants in the ITT from whom both Day 0 and Day 28 data was able to be collected in full. For the IRS, this includes all participants for whom item #8 (overall impairmant) was completed. In the AKL-T01 arm, item #8 was not answered by 4 participants. In the AKL-T09 arm, item #8 was not answered by 3 participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AKL-T01 (EVO Multi) | Impairment Rating Scale, Overall Impairment (Change From Baseline to Posttreatment) | -0.5 score on a scale | Standard Deviation 1.4 |
| AKL-T09 (EVO Words) | Impairment Rating Scale, Overall Impairment (Change From Baseline to Posttreatment) | -0.4 score on a scale | Standard Deviation 1.2 |