Improving Cognitive Health in COVID-19 Survivors

Study Overview
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Brief Summary
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The primary objective of this study is to investigate the efficacy of AKL-T01, a remotely-delivered digital cognitive intervention, relative to a waitlist control in improving cognitive functioning in COVID-19 survivors.

Detailed Description
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Emerging evidence suggests a subgroup of survivors of COVID- 19 have residual difficulties with cognition and daily functioning. These deficits are pronounced in cognitive domains including attention, learning and executive skills, and may continue to impact quality of life after recovery from other COVID-19 symptoms. This study aims to investigate the efficacy of AKL-T01 (Akili Interactive), a remotely-delivered digital cognitive intervention, in targeting and improving cognition and functional outcomes in individuals recovering from COVID-19. The efficacy of the AKL-T01 intervention will be measured relative to a waitlist control group.

Official Title
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Improving Cognitive Health in COVID-19 Survivors Through Digital Therapeutics

Conditions
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Cognitive Dysfunction, Covid19

Intervention / Treatment
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* Device: AKL-T01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18-89 years of age Documentation of a deficit in cognitive function (score > 1 standard deviation below normal range) compared to age-adjusted normative data) on at least one screening measure of attention and executive function (Oral Trail Making Test, Stroop Test, or FrSBe) Previous diagnosis of COVID-19 confirmed via SARS-CoV-2 polymerase chain reaction (PCR) test (or reported experience of COVID-19 symptoms with a documented positive antibody test or clinical diagnosis based on symptoms and accompanying physician's note) documented in the electronic medical record or in other existing medical records Access to and self-report of ability to connect wireless devices to a functional wireless network. Ability to follow written and verbal instructions (English) as assessed by the PI and/or coinvestigator. Able to comply with all testing and study requirements and willingness to participate in the full study duration Exclusion Criteria: History of neurologic disorder prior to COVID-19 diagnosis, such as Parkinson's disease, multiple sclerosis, Alzheimer's disease, stroke, brain tumor, or dementia. History of severe mental illness (e.g., schizophrenia, psychosis, history of suicide attempt in the last year) or substance use disorder, recent history (in the past year) of symptoms of psychosis Participant is currently considered at risk for attempting suicide by the Investigator, has made a suicide attempt within the past year, or is currently demonstrating active suicidal ideation or self-injurious behavior. Motor condition (e.g., physical deformity of the hands/arms) that prevents game playing as reported by the participant or observed by the Investigator Recent history (within 6 months prior to screening/baseline) of substance use disorder History of seizures (excluding febrile seizures), a tic disorder, significant tics, a current diagnosis of Tourette's Disorder. Color blindness as determined by self-report Regular use of psychoactive drugs other than antidepressants or benzodiazepines, including stimulants that in the opinion of the Investigator may confound study data/assessments. Any other acute medical condition that may interfere with participation or interpretation of the results Previous exposure to AKL-T01.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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: This study is a randomized clinical trial designed to compare efficacy of the AKL-T01 intervention relative to a waitlist control in patients who were infected with COVID-19. Participants will be randomized to the AKL-T01 or a waitlist control. We will use a waitlist design; at the end of the intervention period, participants in the control group will have the option to receive the 6-week AKL-T01 intervention.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKL-T01 Intervention<br>Participants in the experimental group will complete 6 weeks of the AKL-T01 intervention. Participants enrolled in the intervention arm will play the game via an iPad application for 20-25 minutes daily for at least 5 days a week (but up to 7 days a week). Participants will also have weekly check-in visits via phone or a secure HIPAA compliant videoconferencing platform (Zoom) with a care manager, who will monitor mood symptoms and gameplay adherence. | Device: AKL-T01<br>* AKL-T01 will be administered as a 6-week intervention. It is an algorithmically delivered iPad-based video game designed to improve cognitive health by targeting attention and attentional control processes.<br>|
| No Intervention: Waitlist Control<br>Participants in the Waitlist Control arm will not be engaging in any active control condition. Participants in the waitlist control arm will continue any ongoing self- or provider-based cognitive intervention (or no intervention) during the initial 6-week waitlist period. Participants will also have weekly check-in visits via phone or a secure HIPAA compliant videoconferencing platform (Zoom) with a care manager, who will monitor mood symptoms. The control arm will be offered the intervention at the end of 6 weeks waitlist period to ensure all participants ultimately have access to the intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive function, as measured by the Digit Symbol Matching Task | Change in cognitive function in the experimental group vs. controls, measured by score on the Digit Symbol Matching Task, a timed measure of attention and processing speed. Participants are asked to correctly match pairs of shapes and numbers. Scores exceeding the normative mean (mean = 65.79) reflect better task performance and scores below the normative mean reflect poorer performance. | Baseline and Post Treatment (6 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in daily functioning, as measured by the NeuroQOL Cognitive Function scale | Change in scores on the NeuroQOL Cognitive Function scale in the experimental group vs. controls. The NeuroQOL Cognitive Function scale is a 28-item self-report measure of daily functioning. Higher scores, defined as those exceeding the normative mean (mean (SD) = 50.09 (10.23)), reflect better self-reported daily cognitive abilities, while lower scores, defined as those falling below the t-score mean of the normative sample, reflect poorer self-reported daily cognitive abilities. | Baseline and Post Treatment (6 weeks) | 
| Change in cognitive performance, as measured by the Multiple Object Tracking test | Change in scores on the Multiple Object Tracking task in the experimental group vs. controls This task measures sustained attention, cognitive control, and working memory, and requires participants to remember and track a set of target circles as they move around the screen, among a larger set of identical distractor circles. The primary outcome measure is the number of dots that a participant was able to track and identify successfully. Higher scores, defined as those exceeding the normative mean (M = 56.94) reflect better performance, while lower scores reflect poorer task performance. | Baseline and Post Treatment (6 weeks) | 
| Change in cognitive performance, as measured by the Digit Span Backwards test | Change in scores on the Test My Brain (TMT) Digit Span Backwards task in the experimental group vs. controls. This task measures sustained attention and working memory. Participants are shown a series of numbers and asked to reproduce them in reverse order. Higher scores, defined as those exceeding the normative mean (M = 5.98) reflect better performance, while lower scores reflect poorer task performance. | Baseline and Post Treatment (6 weeks) | 
| Change in cognitive performance, as measured by the Simple Reaction Time test | Change in scores on the Simple Reaction Time task in the experimental group vs. controls This task measures simple reaction time and psychomotor speed, and requires participants to press a key whenever a green square appears. Higher scores, defined as those exceeding the normative mean (M = 31.71) reflect faster response times, while lower scores reflect slower response times. | Baseline and Post Treatment (6 weeks) | 
| Change in cognitive performance, as measured by the Choice Reaction Time test | Change in scores on the Choice Reaction Time task in the experimental group vs. controls This task measures processing speed and cognitive control, and requires participants to indicate the direction of an arrow that is a different color from the rest. Higher scores, defined as those exceeding the normative mean (M = 11.49) reflect better performance, while lower scores reflect poorer performance. | Baseline and Post Treatment (6 weeks) | 
| Change in cognitive performance, as measured by the Letter-Number Switching test | Change in scores on the Letter-Number Switching task in the experimental group vs. controls This task measures sustained attention and set-shifting, and requires participants to switch between responses to letters and numbers. Lower scores, defined as those below the normative mean (M = 1.06) reflect better set-shifting performance, while higher scores reflect poorer set-shifting performance. | Baseline and Post Treatment (6 weeks) | 
| Change in cognitive performance, as measured by the Gradual Onset Continuous Performance Test | Change in scores on the Gradual Onset Continuous Performance Test in the experimental group vs. controls This task measures sustained attention and response inhibition, and requires participants to respond to specific stimuli and ignore distractors.. Higher scores, defined as those exceeding the normative mean (M = 67.97) reflect better performance, while lower scores reflect poorer performance. | Baseline and Post Treatment (6 weeks) | 
| Change in cognitive performance, as measured by the Visual Paired Associates Task | Change in scores on the Visual Paired Associates Task in the experimental group vs. controls. This task measures visual memory, and requires participants to learn and identify iamge pairs. Higher scores, defined as those exceeding the normative mean (M = 10.53) reflect better performance, while lower scores reflect poorer performance. | Baseline and Post Treatment (6 weeks) | 
| Change in overall daily functioning, as measured by the World Health Organization Disability Assessment Scale (WHODAS) 2.0 | Change in total score on the 36-item WHODAS in the experimental group vs. controls. The WHODAS 2.0 assesses the following domains of functioning: cognition, mobility, getting along, self-care, participation, and life activities. Scores range from 0 (no disability) to 100 (maximum disability), with higher scores reflecting a greater degree of overall functional disability. | Baseline and Post Treatment (6 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid19, Cognitive Dysfunction, Attention Disturbances, Cognitive Change