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

Trial Summary

What is the purpose of this trial?

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 coaching to teach new thinking strategies. It aims to improve mood, thinking skills, and daily functioning.

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.

What data supports the effectiveness of the treatment AKL-T01, an iPad-based cognitive training program, Metacognitive Strategy Training, and Enhanced Metacognitive Strategy Training for post-stroke depression?

Research shows that metacognitive strategy training can improve rehabilitation engagement and daily functioning in stroke patients, and cognitive training has been well received, leading to improvements in everyday functioning. These findings suggest that combining these approaches may help address cognitive and functional challenges in post-stroke depression. ^{1 2 3 4 5}

Is the digital intervention with cognitive strategies safe for humans?

The digital intervention combining cognitive training and metacognitive strategy training has been found to be feasible and acceptable in individuals with chronic stroke, with high satisfaction and completion rates, indicating it is generally safe for humans. ^{3 6 7 8 9}

How is the treatment for post-stroke depression using AKL-T01 and Metacognitive Strategy Training different from other treatments?

This treatment is unique because it combines a digital cognitive training program with metacognitive strategies, which are techniques to help patients think about their own thinking. This approach is different from traditional treatments that may focus solely on medication or talk therapy, as it specifically targets cognitive processes and uses technology to enhance recovery. ^{1 10 11 12 13}

Research Team

Abhishek Jaywant, PhD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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 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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Psychometric properties of the post-stroke depression scale in the sequelae stage. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The feasibility of meta-cognitive strategy training in acute inpatient stroke rehabilitation: case report. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Feasibility of Augmenting Cognitive Strategy Training With Non-Invasive Brain Stimulation. [2023]

4. England 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. [2022]

5. England 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Neurofeedback as a form of cognitive rehabilitation therapy following stroke: A systematic review. [2022]

7. Switzerland 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

The Effects of Computer Based Cognitive Rehabilitation in Stroke Patients with Working Memory Impairment: A Systematic Review. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Online awareness of performance on a functional cognitive assessment in individuals with stroke: A case-control study. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical studies on event-related potentials (ERPs) N400 and the related factors in patients with poststroke depression (PSD). [2017]

11. United States pubmed.ncbi.nlm.nih.gov

Lower cognitive control network connectivity in stroke participants with depressive features. [2020]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Proposing a new stroke-specific screening tool for depression: Examination of construct validity and reliability. [2022]

13. Denmark pubmed.ncbi.nlm.nih.gov

Subthreshold depression and cognitive impairment but not demented in stroke patients during their rehabilitation. [2016]