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

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Of the millions of patients who live through critical illness annually, Intensive Care Unit (ICU)
survivorship is marked by a dementia-like brain injury called post-ICU long-term cognitive impairment
(ICU-LTCI) that creates grave difficulties with managing medications, handling finances, living
independently, and maintaining employment. Data from our group and others show that 50% of ICU
survivors suffer from ICU-LTCI and that the number of veterans who develop ICU-LTCI is as high as
the number of patients with new traumatic brain injury diagnoses among all Active Duty, National
Guard, and Reserves. Our pilot randomized “Returning to Everyday Tasks Utilizing Rehabilitation
Networks-I” (RETURN-I) study showed that a 12-week cognitive rehabilitation intervention (versus
controls) improved executive dysfunction. We then transformed this non-computerized resource-
intensive strategy into a novel, efficient, and scalable Computerized Cognitive Rehabilitation (CCR)
approach. This plasticity-based adaptive CCR was applied to ICU survivors enrolled in our
uncontrolled case-series (RETURN-II) that signaled improvements across multiple cognitive domains.
 Building on nearly two decades of aging brain research with the VA-Tennessee Valley
Healthcare System Geriatric Research, Education and Clinical Center (VA-TVHS GRECC), we
propose this randomized controlled trial to investigate the efficacy of CCR for survivors with ICU-
LTCI. The RETURN-III Study will be the next logical data-driven approach to create real-world
solutions for Veterans and civilians surviving critical illness with disabling ICU-LTCI.
 The RETURN-III Study will test the hypotheses that a 12-week CCR intervention in medical
and surgical ICU survivors will reduce the severity of cognitive impairment (Aim 1), and result in
Magnetic Resonance Imaging (MRI) changes of decreased brain atrophy, greater functional
connectivity, and greater cerebral blood flow (Exploratory Aim 2).
 To test these hypotheses, the RETURN-III study will randomize 160 medical and surgical VA
ICU survivors with documented ICU-LTCI up to 14 days post-hospital discharge to either 12-weeks of
intervention using CCR (n=80) vs. control of non-specific computer games (n=80). At 3, 6, and 12
months post-randomization, trained research personnel blinded to group assignment will use a
validated battery to assess global cognition [primary outcome] (Aim 1: domains of processing
speed, working memory, episodic memory, executive function), and to investigate 12-month MRI
imaging metrics [exploratory outcome] (Aim 2: standard structural and anatomic protocols, baseline
blood oxygenation level dependent responses, pseudo-continuous arterial spin labeling).

## Key facts

- **NIH application ID:** 9951437
- **Project number:** 1I01RX002992-01A2
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** E Wesley ELY
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9951437

## Citation

> US National Institutes of Health, RePORTER application 9951437, Returning to Everyday Tasks Utilizing Rehabilitation Networks-III Pilot Randomized Clinical Trial (RETURN-III Pilot RCT) (1I01RX002992-01A2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9951437. Licensed CC0.

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