Returning to Everyday Tasks Utilizing Rehabilitation Networks-III (RETURN-III)

NCT ID: NCT04353804

Last Updated: 2025-02-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-03
• Study Completion Date: 2026-12-31

Brief Summary

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.

Detailed Description

Over a lifetime, an average American will be admitted to an intensive care unit (ICU) twice, will spend nearly a week in an ICU during their last six months of life, and will have a one in five chance of an ICU-related death. Of those millions who annually survive critical illness, ICU survivorship is marked by an inability to manage medication, handle finances, live independently, and maintain employment due to post-ICU long-term cognitive impairment (ICU-LTCI).

Data from the investigators' group and others show that 50% of ICU survivors suffer from ICU-LTCI. The investigators' Veterans Affairs (VA) Merit Award funded research, "Measuring the Incidence and determining risk factors for Neuropsychological Dysfunction in ICU Survivors" (MIND-ICU) study, helped define the epidemiology of this persistent and progressive chronic brain dysfunction that affects both executive function and memory domains of cognition. Among survivors from medical and surgical ICUs, 40% have impairments rivaling moderate traumatic brain injury, and 30% have impairments similar to mild-moderate Alzheimer's disease. The MIND-ICU study indicates that the number of Veterans who develop ICU-LTCI is as high as the number of new traumatic brain injury diagnoses among all Active Duty, National Guard, and Reserves of the Army, Navy, Air Force and Marine Corps. For a public health problem of this magnitude, there is a driving unmet need to find solutions for ICU-LTCI.

The investigators' pilot randomized "Returning to Everyday Tasks Utilizing Rehabilitation Networks-I" (RETURN-I) Study showed that a 12-week cognitive rehabilitation intervention (vs. controls) improved executive dysfunction. Next, the investigators transformed this non-computerized, resource-intensive strategy into a novel, efficient, and scalable Computerized Cognitive Rehabilitation (CCR) method. This plasticity-based adaptive CCR was applied to a case-series of ICU survivors which signaled improvements across multiple cognitive domains.

Building on nearly two decades of aging brain research with the VA-Tennessee Valley Geriatric Research, Education and Clinical Center (GRECC), the investigators now propose a Phase II randomized controlled trial (RCT) to investigate the efficacy of CCR for survivors with ICU-LTCI. The Returning to Everyday Tasks Utilizing Rehabilitation Networks-III Study (RETURN-III Study) will be the next logical data-driven approach to develop and offer innovative real-world solutions for civilians and Veterans surviving critical illness with disabling ICU-LTCI.

To test these hypotheses, the RETURN-III study will randomize medical and surgical VA ICU survivors to either intervention using CCR, or control of non-specific computer games. At three, and twelve months post-randomization, trained research personnel blinded to group assignment will use a validated battery to assess global cognition [primary outcome].

Conditions

Cognitive Rehabilitation; ICU Survivorship; Intensive Care Unit; ICU

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Computerized Cognitive Rehabilitation

Computerized Cognitive Rehabilitation

Group Type: EXPERIMENTAL

Treatment Arm: Computerized Cognitive Rehabilitation

Intervention Type: OTHER

Treatment Arm: Computerized Cognitive Rehabilitation

Active Control computer games

Active Control computer games

Group Type: ACTIVE_COMPARATOR

Active Control computer games

Intervention Type: OTHER

Active Control computer games

Interventions

Treatment Arm: Computerized Cognitive Rehabilitation

Treatment Arm: Computerized Cognitive Rehabilitation

Intervention Type: OTHER

Active Control computer games

Active Control computer games

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adults with a recent ICU stay (Medical or Surgical) requiring treatment for respiratory failure and/or shock (i.e., high-risk population)
• No longer requiring ICU-level care

Exclusion Criteria

• No history of pre-existing severe cognitive impairment (IQCODE<3.3, documentation in medical record)
• Unwilling to commit to participation in the intervention
• Under consideration for hospice
• Primary residence over 100 miles from enrolling site if the patient is unwilling to return to the enrolling site for follow-up
• Homeless without a secondary contact available
• Severe substance abuse or neuropsychiatric disorder of a severity that prevents independent living
• Active suicidal ideation
• Any past or present behavior that may be deemed a safety risk for follow-up
• Blind, deaf, or unable to understand/communicate in English
• Required ICU level care less than 24 hours
• Not capable of completing computer-based training

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

E. Wesley Ely, MD MPH

Role: PRINCIPAL_INVESTIGATOR

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Mayur B Patel, MD MPH

Role: PRINCIPAL_INVESTIGATOR

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Locations

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, United States

Site Status: RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mayur B Patel, MD MPH

Role: CONTACT

Mayur.Patel2@va.gov

(615) 873-7214

E. Wesley Ely, MD MPH

Role: CONTACT

wes.ely@vumc.org

(615) 873-6055

Facility Contacts

Matthew G Francis

Role: primary

matthew.francis@va.gov

615-873-8694 ext. 68694

Ray Stokes Peebles, MD

Role: backup

Ray.Peebles@va.gov

(615) 327-4751

Mayur B Patel, MD

Role: primary

mayur.b.patel@vumc.org

615-322-5000

E. Wesley Ely, MD

Role: backup

wes.ely@vumc.org

6153225000

Other Identifiers

1506673-1

Identifier Type: OTHER

Identifier Source: secondary_id

I01RX002992-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

230960

Identifier Type: OTHER

Identifier Source: secondary_id

D2992-R

Identifier Type: -

Identifier Source: org_study_id