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

Returning to Everyday Tasks Utilizing Rehabilitation Networks-III Pilot Randomized Clinical Trial (RETURN-III Pilot RCT)

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.

Study Overview

• Status: Recruiting
• Conditions: Intensive Care Unit; ICU; Cognitive Rehabilitation; ICU Survivorship
• Intervention / Treatment: Other: Treatment Arm: Computerized Cognitive Rehabilitation; Other: Active Control computer games

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].

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mayur B Patel, MD MPH; Phone Number: (615) 873-7214; Email: Mayur.Patel2@va.gov
• Study Contact Backup: Name: E. Wesley Ely, MD MPH; Phone Number: (615) 873-6055; Email: wes.ely@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Mayur B Patel, MD; Phone Number: 615-322-5000; Email: mayur.b.patel@vumc.org
      • Contact: E. Wesley Ely, MD; Phone Number: 6153225000; Email: wes.ely@vumc.org
    • Nashville, Tennessee, United States, 37212-2637
      • Recruiting
      • Tennessee Valley Healthcare System Nashville Campus, Nashville, TN
      • Contact: Matthew G Francis; Phone Number: 68694 615-873-8694; Email: matthew.francis@va.gov
      • Principal Investigator: E. Wesley Ely, MD MPH
      • Principal Investigator: Mayur B Patel, MD MPH
      • Contact: Ray Stokes Peebles, MD; Phone Number: (615) 327-4751; Email: Ray.Peebles@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Computerized Cognitive Rehabilitation	Other: Treatment Arm: Computerized Cognitive Rehabilitation; Treatment Arm: Computerized Cognitive Rehabilitation
Active Comparator: Active Control computer games	Other: Active Control computer games; Active Control computer games

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Cognitive Composite Score	Global Cognitive Composite Score derived from the composite score provided by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, range 40-160). The higher the number, the better the outcome.	3 months

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Vanderbilt University Medical Center
• Investigators: Principal Investigator: E. Wesley Ely, MD MPH, Tennessee Valley Healthcare System Nashville Campus, Nashville, TN; Principal Investigator: Mayur B Patel, MD MPH, Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 16, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: ICU; Intensive Care Unit; Cognitive Rehabilitation; ICU Survivorship
• Other Study ID Numbers: D2992-R; 1506673-1 (Other Identifier: TVHS IRB); I01RX002992-01A2 (U.S. NIH Grant/Contract); 230960 (Other Identifier: VUMC IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators will share data de-identified after study publication in accordance to clinical trial best practices and complying with federal guidelines for research.
• IPD Sharing Time Frame: We will share data de-identified >12 months after study publication in accordance to clinical trial best practices and complying with federal guidelines for research.
• IPD Sharing Access Criteria: We will share data de-identified after study publication in accordance to clinical trial best practices and complying with federal guidelines for research for an unlimited period of time.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No