Development of Virtual Reality-based Interventions to Strengthen Cognitive Skillsets Related to Attention Deficit Hyperactivity Disorder (ADHD): A Pilot Phase I and Randomized Controlled Phase II Trial

Study Description: This study will be a randomized double-blind placebo-controlled trial examining the efficacy of a novel virtual reality (VR) adaptive cognitive training intervention for youth with ADHD in improving symptoms of inattention relative to a non-adaptive training control intervention. Prior to the main randomized trial, a proof-of concept open-label pilot study will assess the safety, tolerability, usability, feasibility, credibility and treatment expectancy of the intervention. It will also provide an initial assessment of the efficacy on the intervention in improving inattention symptoms and neuropsychological performance.When these parameters are met, the pilot will be complete and the RCT will begin.

Objectives:

Primary Objective: Examine the efficacy of the Floreo VR intervention in improving symptoms of inattention in children/adolescents with ADHD.

Secondary Objectives: Examine the efficacy of the VR intervention in improving neuropsychological performance in four cognitive domains pertinent to ADHD.

Pilot Study Objective: Assess the safety, tolerability, usability, feasibility, credibility and treatment expectancy of the VR intervention. Provide an initial open-label assessment of the efficacy of the intervention.

Endpoints:

Primary Endpoint: The primary endpoint of the main trial is to investigate whether the intervention decreases symptoms of inattention as assessed using the ADHD Rating Scale-5 for Children and Adolescents (ADHD-RS-5).

A secondary aim of the main study is to investigate whether the intervention brings about improvements in performance on four neuropsychological performance indices. These are stop signal reaction time on the Stop Signal task (inhibitory control), visuospatial working memory as determined using number of correct responses on the Dot Matrix task, a composite measure of temporal deviation on a Temporal Reproduction task, and the number of correct responses on the NIH Toolbox Pattern Comparison Processing Speed Test.

Pilot intervention Endpoints: Responses to structured interview items on safety, tolerability, usability, credibility and treatment expectancy of the intervention. Reports of adverse events will be used to assess safety. Feasibility will be assessed using participation and compliance rates. Usability will also be assessed using a System Usability Scale. Open-label assessments of efficacy will also be performed, using the ADHD-RS-5 inattention subscale. Secondary endpoints for the pilot study are the same as for the main study.

• INCLUSION CRITERIA:

In order to be eligible to participate, an individual must meet all of the following criteria:

• Children must provide informed assent and parents must provide informed consent to participate in the study.
• Any sex assigned at birth, or race/ethnicity.
• Aged between 8 and 16 years of age, including all months leading up to age 17.
• Meets diagnosis for ADHD, predominately inattentive or combined presentations, or a specified presentation of having prominent symptoms of inattention that are impairing in two or more settings (but not numerous enough to meet a diagnosis of inattentive or combined presentation).
• Stated willingness to comply with all study procedures and lifestyle considerations and availability for the duration of the study.
• For the Pilot only: If treated for ADHD with psychostimulants, willing to withdraw medication three days prior to baseline assessments and to stay off medication until completion of the post-intervention assessment. Not receiving any other psychotropic medication for at least 30 days prior to baseline assessment.

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Cognitively not capable of performing study procedures. Indications of a lack of cognitive capacity could include a known IQ under 70, or a history from the screening interview that implies global intellectual disabilities (e.g., placement in a school for children with intellectual disability etc.)
• History of severe migraines, vertigo, epilepsy (with the exception of febrile seizures), or serious balance disorders.
• Impairments in uncorrected visual acuity that would interfere with engagement with the VR training.
• Known to be pregnant.
• Psychotic disorders (including schizophrenia, psychosis not otherwise specified), current substance dependence. Other psychiatric disorders elicited on the interview are not considered exclusionary provided that ADHD is considered to be one of the dominant sources of impairment for the child.
• Considered a suicide risk as determined during the clinical interview at baseline.
• Any other medical or psychiatric condition that in the opinion of the PI may confound study data/assessments (e.g., limitations in mobility that would render the VR headset unusable).
• Recent (within three months) treatment with other cognitive training interventions (e.g., Cogmed) for ADHD.
• The VR equipment produces excessive discomfort to the child in the opinion of the PI (e.g., including participants with small interpupillary distances (IPD) that are only able to see blurry images on the VR headset, or children showing signs of undue neck and upper body strain or fatigue while trying the headset).
• For the main trial only: Certain psychotropic medications classes that are likely to interfere with the completion of the intervention are exclusionary: antipsychotics, mood stabilizers (lithium, valproate, lamotrigine, gabapentin). Medications for ADHD will not be considered as exclusionary. This includes psychostimulants, atomoxetine, alpha 2 adrenergic agonists. Antidepressant and anxiolytic medication will also not be exclusionary if they are deemed not to not interfere with study procedures
• For the main trial only: Prior use of Floreo s products including but not limited to their ADHD cognitive training application.