Digital Intervention + Cognitive Strategies for Post-Stroke Depression

Overseen By Alexandra Keenan, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: Antidepressants

Disqualifiers: Receptive aphasia, Dementia, Psychosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals who have experienced a stroke and face depression and cognitive challenges. The treatment combines an iPad-based game (AKL-T01) designed to enhance multitasking with weekly coaching sessions to improve daily activities and emotions. It aims to boost cognitive skills, elevate mood, and enhance daily life. Individuals who had their first stroke over six months ago, experience depression, and can use an iPad might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but if you are on an antidepressant, you must be on a stable dose for at least 8 weeks before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that AKL-T01, a video game for the iPad, is designed to improve thinking skills and mood. Earlier studies tested this game with stroke patients experiencing depression and cognitive issues. The research suggests that AKL-T01 is generally safe and well-tolerated, with no major reports of harmful side effects.

Since this study is in an early stage, it focuses on assessing the treatment's safety and effectiveness. This phase usually involves a smaller group of participants to closely monitor any issues. The goal is to ensure the treatment's safety before testing it with a larger group.

Overall, current evidence suggests that the AKL-T01 treatment is promising in terms of safety. However, as with any trial, researchers monitor participants to ensure their well-being throughout the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the AKL-T01 treatment for post-stroke depression because it introduces a novel, game-based approach to cognitive therapy. Unlike traditional treatments that often involve medication or standard talk therapy, AKL-T01 immerses patients in a video game-like environment that enhances multitasking skills and cognitive flexibility. This interactive method is paired with metacognitive strategy coaching, which helps participants apply their in-game experiences to real-life situations. This combination of digital intervention and reflective strategy coaching could offer a more engaging and personalized way to address cognitive and emotional challenges after a stroke.

What evidence suggests that this trial's treatments could be effective for post-stroke depression?

This trial will compare the effects of AKL-T01, a video game on an iPad, with Enhanced Metacognitive Strategy Training for post-stroke depression. Studies have shown that playing AKL-T01 can improve thinking skills and reduce depression after a stroke. The game focuses on skills needed to manage tasks and emotions. Research indicates that AKL-T01 strengthens brain connections, which may weaken after a stroke. This digital method aims to boost both mood and cognitive abilities. Initial findings suggest it could help with common post-stroke challenges. ^{1 2 4 5 6}

Who Is on the Research Team?

Abhishek Jaywant, PhD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for individuals who had their first stroke at least 6 months ago and are now experiencing moderate depression and executive dysfunction. They must be able to use an iPad, not have severe language or speech impairments, no major neurological conditions other than stroke, and if on antidepressants, they should be on a stable dose for at least 8 weeks.

Inclusion Criteria

Able to adhere to all testing and study requirements and willingness to participate in the full study duration

I have been on the same dose of antidepressant for at least 8 weeks.

You have significant symptoms of depression, as measured by a specific scale, called the Montgomery Asberg Depression Rating Scale, with a score of 18 or higher.

Exclusion Criteria

You have a history of severe mental illness like psychosis or mania.

You have severe problems with seeing or paying attention to half of your visual field.

I have a significant neurological condition, but not a stroke.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the digital intervention (AKL-T01) and metacognitive strategy coaching for post-stroke depression and executive dysfunction

6 weeks

Weekly virtual coaching sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AKL-T01
• Metacognitive Strategy Training

Trial Overview The study tests a digital therapeutic (iPad-based cognitive training) combined with metacognitive strategy training. It aims to improve cognitive skills, alleviate symptoms of depression, enhance daily functioning, and potentially affect brain connectivity in post-stroke patients.

How Is the Trial Designed?

Group I: AKL-T01 Experimental Treatment 2 Interventions

Participants in the intervention group will complete 25 minutes of AKL-T01 per day, 5 days/week, for 6 weeks. AKL-T01 trains rapid multitasking on an iPad in an immersive videogame-like environment. Participants complete go/no-go + navigation exercises by moving the iPad to navigate a character on a path while tapping when a certain stimulus is presented and ignoring other stimuli. Participants will also receive weekly 45-minute metacognitive strategy coaching sessions delivered by a clinician. Sessions use guided questions and worksheets (shared virtually) to help participants reflect on their experience with AKL-T01 and link it to daily functioning, generate strategies for daily activities, and explore any emotional responses that arise during gameplay.

Group II: Enhanced Metacognitive Strategy Training Placebo Group 1 Intervention

In the control group, participants will complete-at the same frequency and duration as the intervention group-iPad-based games designed to provide general cognitive stimulation (word searches, checkers, and "spot the differences" between two pictures). Concurrently with these cognitive stimulation games, participants will receive weekly metacognitive strategy coaching sessions akin to that described above.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

The Post-Stroke Depression Scale in the Sequelae Stage (PSDS-SS) was developed and validated with a study involving 716 stroke patients, demonstrating a stable 5-factor structure and good reliability and validity for assessing post-stroke depression.

The final version of the PSDS-SS consists of 21 items, making it an effective screening tool for identifying post-stroke depression in patients during the sequelae stage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychometric properties of the post-stroke depression scale in the sequelae stage. Zeng, Y., Li, F., Ning, L., et al.[2023]

In stroke patients, the prevalence of depressive symptoms and cognitive impairment was notably high, with 60% and 54% respectively upon admission, indicating a critical need for early detection and intervention during rehabilitation.

Factors such as recurrent strokes, cognitive impairment at admission, and dependence in activities of daily living were strongly associated with ongoing depressive symptoms at 6 months post-stroke, highlighting the importance of continuous screening to improve rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthreshold depression and cognitive impairment but not demented in stroke patients during their rehabilitation. Saxena, SK., Ng, TP., Yong, D., et al.[2016]

A telehealth-based intervention combining computerized cognitive training and metacognitive strategies was developed to help individuals with executive dysfunction after stroke, addressing barriers to access due to mobility challenges.

Preliminary results from three participants showed high satisfaction and credibility of the treatment, with a median completion rate of 96% for cognitive training sessions, indicating that this approach may be feasible and acceptable for stroke survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Acceptability of a Remotely Delivered Executive Function Intervention That Combines Computerized Cognitive Training and Metacognitive Strategy Training in Chronic Stroke. Jaywant, A., Mautner, L., Waldman, R., et al.[2023]

Meta-cognitive strategy training, specifically the CO-OP method, was successfully implemented during inpatient rehabilitation for a patient with cognitive impairments after a right hemisphere stroke, showing its feasibility in a clinical setting.

The participant demonstrated significant improvements in rehabilitation engagement and functional independence, with notable increases in performance scores across various measures, suggesting potential benefits of this training approach for stroke recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of meta-cognitive strategy training in acute inpatient stroke rehabilitation: case report. Skidmore, ER., Holm, MB., Whyte, EM., et al.[2021]

In a study of 96 ischemic stroke inpatients, high self-efficacy and strong social support were identified as the most protective factors against developing post-stroke depression (PSD) during the acute phase after stroke.

Cognitive functioning's impact on depressive symptoms was fully mediated by general self-efficacy, indicating that enhancing self-efficacy may be crucial in preventing PSD in rehabilitation settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of self-efficacy, pre-stroke depression and perceived social support on self-reported depressive symptoms during stroke rehabilitation. Lewin, A., Jöbges, M., Werheid, K.[2022]

In patients with poststroke depression (PSD), significant differences were found in event-related potentials (ERPs) N400, with prolonged incubation periods and reduced average amplitudes compared to stroke patients without depression, indicating altered brain processing related to depression.

After 3 months of treatment with fluoxetine, PSD patients showed improvements in N400 parameters and increased blood platelet 5-HT concentrations, suggesting that serotonin levels may play a role in the efficacy of treatment and the neurophysiological changes associated with PSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical studies on event-related potentials (ERPs) N400 and the related factors in patients with poststroke depression (PSD). He, W., Cai, D., Lin, L., et al.[2017]

In a study of 64 stroke patients, those with depressive features showed significantly lower connectivity between the left dorsolateral prefrontal cortex (DLPFC) and the right supramarginal gyrus, indicating a disruption in the cognitive control network associated with post-stroke depression.

These findings suggest that post-stroke depression is linked to network-level changes in brain connectivity rather than just lesions in the DLPFC, highlighting the complexity of depression as a network disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower cognitive control network connectivity in stroke participants with depressive features. Egorova, N., Cumming, T., Shirbin, C., et al.[2020]

The study proposes a new screening tool, the HRQOLISP-E, specifically designed to identify post-stroke depression (PSD) in recent stroke survivors, showing strong construct validity and reliability compared to the Hospital Anxiety and Depression Scale (HADS-D).

The HRQOLISP-E demonstrated significant correlations with depression levels, age, and stroke severity, indicating it may be a more effective tool for assessing depression in stroke patients than existing measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proposing a new stroke-specific screening tool for depression: Examination of construct validity and reliability. Ojagbemi, A., Owolabi, M., Akinyemi, J., et al.[2022]

Neurofeedback therapy (NFT) shows promise in improving cognitive deficits in stroke patients, with most of the eight studies reviewed reporting positive outcomes after therapy initiation.

However, the overall quality of the studies was limited, which affects the reliability of the findings, highlighting the need for better-designed research and standardized NFT protocols to fully understand its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback as a form of cognitive rehabilitation therapy following stroke: A systematic review. Renton, T., Tibbles, A., Topolovec-Vranic, J.[2022]

Stroke patients often overestimate their performance on cognitive tasks, such as the Weekly Calendar Planning Activity (WCPA-10), indicating a lack of awareness about their cognitive abilities during rehabilitation.

Improving metacognitive awareness—understanding one's own performance—should be a key focus in cognitive rehabilitation for stroke patients, as poor awareness is linked to worse task performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Online awareness of performance on a functional cognitive assessment in individuals with stroke: A case-control study. Jaywant, A., Arora, C., Toglia, J.[2022]

In a study involving 80 stroke patients, 4 weeks of online adaptive attention training (SAT) led to significant improvements in everyday functioning, particularly for those with spatial impairments, compared to working memory training and a waitlist group.

While no significant changes were observed in cognitive test performance, the positive patient-reported outcomes suggest that SAT may be a valuable low-cost adjunct to rehabilitation services for enhancing daily life after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized control trial of the effects of home-based online attention training and working memory training on cognition and everyday function in a community stroke sample. Peers, PV., Punton, SF., Murphy, FC., et al.[2023]

A systematic review of computer-based cognitive rehabilitation (CBCR) for working memory impairment after stroke found insufficient evidence to determine its effectiveness, as studies showed highly variable results and used different measures of working memory.

No harmful effects were reported from CBCR interventions, but the lack of meaningful differences in working memory improvement compared to control groups suggests that more research is needed to assess its true benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Computer Based Cognitive Rehabilitation in Stroke Patients with Working Memory Impairment: A Systematic Review. Niemeijer, M., Sværke, KW., Christensen, HK.[2020]

The combination of metacognitive strategy training (MCST) and transcranial direct current stimulation (tDCS) was found to be feasible and well-accepted by chronic stroke participants, with 12 sessions conducted over 4 weeks.

Participants showed significant improvements in both performance and satisfaction regarding their occupational goals, indicating that this intervention could effectively enhance daily life tasks post-stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Augmenting Cognitive Strategy Training With Non-Invasive Brain Stimulation. Boone, AE., Noe, J., Wolf, TJ.[2023]

Citations

1. withpower.com withpower.com/trial/phase-2-stroke-10-2022-dc1dd

Digital Intervention + Cognitive Strategies for Post-Stroke ... This trial tests a new treatment for stroke patients with depression and thinking problems. The treatment uses an iPad app to train the brain and online ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7481559/

An iPad application-based intervention for improving post ... The iPad application intervention lasts 3 min a day, and the usual rehabilitation lasts 3 h a day. The primary outcome is the change from baseline in The Center ...

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/387821

A Digital Intervention for Post-Stroke Depression and ... AKL-T01 is an iPad-based video game designed to improve executive dysfunction and depression symptoms by targeting executive skills ( ...

4. reporter.nih.gov reporter.nih.gov/project-details/10873174

Project Details - NIH RePORTER AKL-T01 is designed to target a common mechanism underlying post-stroke depressive symptoms and executive dysfunction, which is reduced intrinsic functional ...

5. jcto.weill.cornell.edu jcto.weill.cornell.edu/open_clinical_trials/a-digital-intervention-for-post-stroke-depression-and-executive-dysfunction

A Digital Intervention for Post-Stroke Depression and ... The purpose of this study is to compare the effect of an experimental intervention called “AKL-T01” (a mobile computerized cognitive training program) with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03864484

iPad Application-based Intervention for Post-stroke ... We plan to conduct a randomized controlled trial to examine whether usual rehabilitation plus an iPad application-based intervention improves post-stroke ...