Computerized Cognitive Rehabilitation for ICU Survivorship

(RETURN-III Trial)

Recruiting at 1 trial location

Overseen By Mayur B Patel, MD MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Disqualifiers: Severe cognitive impairment, Hospice, Substance abuse, Suicidal ideation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

160 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Computerized Cognitive Rehabilitation for ICU Survivorship?

Research shows that early cognitive rehabilitation training can significantly improve planning, decision-making, and executive function in ICU patients with cognitive impairment. Additionally, early rehabilitation in the ICU may reduce complications associated with post-intensive care syndrome, which includes cognitive impairments. ^{1 2 3 4 5}

Is computerized cognitive rehabilitation safe for humans?

Research on computerized cognitive rehabilitation, including studies on brain injury and stroke patients, shows it is generally safe. Some patients experienced mild side effects like mental fatigue, headache, and eye irritation, but overall, it was well-tolerated. ^{6 7 8 9 10}

How is Computerized Cognitive Rehabilitation different from other treatments for ICU survivorship?

Computerized Cognitive Rehabilitation is unique because it uses computer programs to help improve cognitive functions like memory and attention, offering a flexible and individualized approach compared to traditional methods like pen and paper exercises. This treatment is particularly novel as it allows for personalized therapy that can be adjusted to the specific needs of each patient, potentially enhancing recovery outcomes. ^{9 10 11 12 13}

What is the purpose of this trial?

Millions of patients survive care in medical and surgical Intensive Care Units (ICUs) every year, only to suffer from a new or accelerated dementia-like process, called post-ICU long-term cognitive impairment (ICU-LTCI). ICU-LTCI causes considerable problems with personal relationships, return to work, and everyday tasks, such as managing medicines and money. No treatment for these patients is currently available. Technology using computerized cognitive rehabilitation could improve ICU-LTCI by harnessing the healing potential of the brain (i.e., neuroplasticity). This intervention is scalable, portable, and economical. The investigators will evaluate the effectiveness of computerized cognitive rehabilitation in a randomized controlled trial of 160 VA patients with ICU-LTCI. The investigators hypothesize that this intervention could improve cognition, and brain structure shown by MRI. This research has high potential to influence rehabilitation strategies for Veteran and civilian ICU survivors.

Research Team

E. Wesley Ely, MD MPH

Principal Investigator

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Mayur B Patel, MD MPH

Principal Investigator

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Eligibility Criteria

This trial is for adults who've recently been in an ICU due to respiratory failure or shock, are now stable, and live close enough to the study site. It's not for those with severe pre-existing cognitive issues, substance abuse problems that prevent independent living, active suicidal thoughts, or sensory impairments that hinder communication.

Inclusion Criteria

I was recently in the ICU for severe breathing problems or shock.

No longer requiring ICU-level care

Exclusion Criteria

Homeless without a secondary contact available

You have a severe substance abuse problem or mental illness that makes it difficult for you to live independently.

I am currently having thoughts about harming myself.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Computerized Cognitive Rehabilitation or active control computer games

12 weeks

Follow-up

Participants are monitored for cognitive improvements and safety post-treatment

12 months

Assessments at 3 and 12 months post-randomization

Treatment Details

Interventions

• Computerized Cognitive Rehabilitation

Trial Overview The RETURN-III trial tests computerized cognitive rehabilitation on patients with post-ICU cognitive impairment. Participants will be randomly assigned to either play control computer games or undergo targeted cognitive rehab exercises designed to improve brain function and structure.

Participant Groups

Group I: Computerized Cognitive Rehabilitation Experimental Treatment 1 Intervention

Computerized Cognitive Rehabilitation

Group II: Active Control computer games Active Control 1 Intervention

Active Control computer games

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

Findings from Research

Long-term cognitive impairment affects up to 60% of ICU survivors, highlighting the need for early functional and cognitive rehabilitation interventions during their ICU stay.

This systematic review aims to evaluate various rehabilitation interventions and their impact on cognitive function, quality of life, and mortality rates 6-12 months post-ICU discharge, setting the stage for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional and cognitive rehabilitation interventions during intensive care admission: A protocol for a systematic integrative review. Collet, MO., Laerkner, E., Jensen, J., et al.[2023]

A pilot study involving 87 ICU patients showed that early cognitive therapy combined with physical therapy was feasible and safe, with 95% of patients receiving the cognitive therapy as planned.

Despite the successful implementation of the therapy, there were no significant differences in cognitive, functional, or quality of life outcomes among the different treatment groups at the 3-month follow-up, indicating that further research is needed to assess the benefits of cognitive therapy in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial. Brummel, NE., Girard, TD., Ely, EW., et al.[2023]

Early rehabilitation interventions in the ICU can significantly reduce the physical and mental health impairments associated with post-intensive care syndrome (PICS), which can negatively affect survivors' quality of life.

Effective rehabilitation requires a multidisciplinary team approach and consideration of factors such as safety, feasibility, and available resources, with specific mental health strategies including ICU diaries and coping skills training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Rehabilitation in the Intensive Care Unit: Preventing Physical and Mental Health Impairments. Parker, A., Sricharoenchai, T., Needham, DM.[2022]

A study involving 136 critically ill patients showed that early cognitive rehabilitation training significantly improved cognitive function after 6 months, with scores in the intervention group being higher than in the control group (26.69 vs. 23.03).

The intervention group also experienced notable improvements in quality of life across various domains, including physical functioning and mental health, indicating that cognitive rehabilitation can enhance overall well-being in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of early cognitive rehabilitation training on cognitive function and quality of life in critically ill patients with cognitive impairment: A randomised controlled trial. Dong, Q., Yang, Y., Tang, Q., et al.[2023]

A proof-of-concept study involving 20 critically ill patients showed that daily 20-minute virtual reality neurocognitive stimulation sessions were feasible and safe, with no adverse events reported during the intervention.

Heart rate variability analysis indicated that the exercises effectively stimulated attention and working memory, and patients found the sessions enjoyable and not overly tiring, suggesting potential for future neurocognitive rehabilitation in critical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and safety of virtual-reality-based early neurocognitive stimulation in critically ill patients. Turon, M., Fernandez-Gonzalo, S., Jodar, M., et al.[2020]

The study identified four key facilitators that help ensure treatment fidelity in computerized cognitive training (CCT) for heart failure patients, including proper training for facilitators, a supportive work environment, a clear implementation guide, and the confidence of the intervenors.

Conversely, three main barriers were noted that could hinder treatment fidelity: technical issues, logistical challenges, and the characteristics of the patient sample, highlighting areas for improvement in future CCT interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceived Facilitators and Barriers to Treatment Fidelity in Computerized Cognitive Training Interventions. Algashgari, EY., Jung, M., Von Ah, D., et al.[2023]

In a study of 39 stroke survivors, computerized cognitive training (CCT) using Lumosity software led to significant improvements in global cognitive function and specific cognitive skills like verbal working memory and processing speed after 12 weeks of training.

While CCT showed immediate cognitive benefits that were maintained for 4 weeks, it did not significantly affect daily activities or participation, and no major differences were found when compared to conventional cognitive training methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of computerized cognitive training on cognitive function, activity, and participation in individuals with stroke: A randomized controlled trial. Ho, HY., Chen, MD., Tsai, CC., et al.[2022]

This pilot study aims to evaluate the effectiveness of a customized tele-rehabilitation platform (GNPT®) for cognitive training in chronic stroke patients, with a focus on improving attention, memory, and executive functions over six weeks with five sessions per week.

The study uses a randomized controlled crossover design, allowing participants to experience both the experimental and sham interventions, which will help determine if personalized cognitive rehabilitation can significantly enhance cognitive function and quality of life for stroke survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A customized home-based computerized cognitive rehabilitation platform for patients with chronic-stage stroke: study protocol for a randomized controlled trial. Gil-Pagés, M., Solana, J., Sánchez-Carrión, R., et al.[2023]

In a study of 34 patients with cognitive dysfunction after traumatic brain injury (TBI), those who underwent 30 sessions of computerized cognitive rehabilitation showed significant improvements, particularly younger patients who excelled in various cognitive tests compared to older patients.

The results suggest that age influences the effectiveness of computerized cognitive rehabilitation, with younger individuals benefiting more in areas like verbal memory and attention, while older patients showed limited improvement, indicating a need for further research with larger sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of computerized cognitive rehabilitation in comparison between young and old age after traumatic brain injury. Kim, SH., Gwak, DW., Jeong, JG., et al.[2023]

The RehaCom computerized cognitive training program significantly improved attention and memory functions in 50 brain injury patients after 60 training sessions, with all patients showing enhanced performance in the targeted areas.

The program was well-tolerated, with no reported negative effects such as mental fatigue, headache, or eye irritation, indicating its safety for use in rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical impact of RehaCom software for cognitive rehabilitation of patients with acquired brain injury. Fernández, E., Bringas, ML., Salazar, S., et al.[2022]

Cognitive rehabilitation for brain-injured patients is increasingly utilizing computer-assisted therapy, with 73% of surveyed rehabilitation centers incorporating computers to address various cognitive deficits such as attention, memory, and problem-solving.

Effective computer-assisted therapy requires careful supervision by therapists, including detailed patient assessments and individualized software adaptations to optimize treatment outcomes, particularly during rehabilitation and post-rehabilitation phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Microcomputer and rehabilitation of cognitive cerebral performance disorders]. Schönle, PW., Wiebold, G., Wieding, J., et al.[2015]

A new cognitive rehabilitation tool, CoRe, was developed to automate and personalize rehabilitation exercises for patients with cognitive impairments, tested on 38 healthy volunteers and 9 patients, showing favorable ratings and suggestions for improvement.

The tool aims to enhance patient compliance, especially among elderly individuals, by providing a variety of exercises and plans to evolve into a telerehabilitation system for home therapy, ensuring continuity of care and reducing costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computer-based cognitive rehabilitation: the CoRe system. Alloni, A., Sinforiani, E., Zucchella, C., et al.[2018]

A randomized controlled study involving service members with combat-related cognitive symptoms found that only 18 out of 120 eligible participants completed a 6-week computer-based cognitive training program, highlighting significant challenges in recruitment and retention.

To improve future studies, the authors suggest design changes such as broader inclusion criteria, the use of a sham control group, and more flexible scheduling to enhance participant compliance and overall feasibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computer-based cognitive rehabilitation research in a military treatment facility: Recruitment, compliance, and lessons learned. Sullivan, KW., Solomon, NP., Pramuka, M., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Functional and cognitive rehabilitation interventions during intensive care admission: A protocol for a systematic integrative review. [2023]

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

Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial. [2023]

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

Early Rehabilitation in the Intensive Care Unit: Preventing Physical and Mental Health Impairments. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Effects of early cognitive rehabilitation training on cognitive function and quality of life in critically ill patients with cognitive impairment: A randomised controlled trial. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Feasibility and safety of virtual-reality-based early neurocognitive stimulation in critically ill patients. [2020]

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

Perceived Facilitators and Barriers to Treatment Fidelity in Computerized Cognitive Training Interventions. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of computerized cognitive training on cognitive function, activity, and participation in individuals with stroke: A randomized controlled trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

A customized home-based computerized cognitive rehabilitation platform for patients with chronic-stage stroke: study protocol for a randomized controlled trial. [2023]

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

Effect of computerized cognitive rehabilitation in comparison between young and old age after traumatic brain injury. [2023]

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

Clinical impact of RehaCom software for cognitive rehabilitation of patients with acquired brain injury. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

[Microcomputer and rehabilitation of cognitive cerebral performance disorders]. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Computer-based cognitive rehabilitation: the CoRe system. [2018]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Computer-based cognitive rehabilitation research in a military treatment facility: Recruitment, compliance, and lessons learned. [2018]