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Cognitive RehabilitationRETURN-IIINCT04353804

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

A study testing Treatment Arm: Computerized Cognitive Rehabilitation in people with Cognitive Rehabilitation and ICU Survivorship, run by VA Office of Research and Development at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Treatment Arm: Computerized Cognitive Rehabilitation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
2 sitesUnited States
Study dates
3 Oct 2022to 31 Jul 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • History of pre-existing severe cognitive impairment (IQCODE>=3.8 or 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
Show all 13Show fewer
  • 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
  • Co-enrollment in another study
  • Incarcerated

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

    Nashville, Tennessee, 37212-2637

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212

Other trials in United States

About this study

Official title: 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 ICU survivors. The investigators hypothesize that this intervention could improve cognition. This research has high potential to influence rehabilitation strategies for Veteran and civilian ICU survivors.

Read the 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 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].

Being tested
Treatment Arm: Computerized Cognitive Rehabilitation, Active Control computer games
Keywords
Cognitive Rehabilitation, ICU Survivorship, Intensive Care Unit, ICU

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Treatment Arm: Computerized Cognitive RehabilitationOther

    Treatment Arm: Computerized Cognitive Rehabilitation

  • Active Control computer gamesOther

    Active Control computer games

Study groups in NCT04353804
Study groupRoleWhat they receive
Computerized Cognitive RehabilitationExperimentalComputerized Cognitive Rehabilitation
Receives: Other: Treatment Arm: Computerized Cognitive Rehabilitation
Active Control computer gamesActive comparatorActive Control computer games
Receives: Other: Active Control computer games

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 3 months

Secondary outcomes (4)

  1. Disabilities in Instrumental Activities in Daily Living (IADLs)

    Measured by Functional Assessment Questionnaire (FAQ)

    Measured: 3 and 12 months

  2. 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.

    Measured: 12 months

  3. Trail Making Test (TMT) Part B

    Evaluation of processing speed and executive function

    Measured: 3 and 12 months

  4. Cognitive Self Report Questionnaire (CSRQ)

    Self-perceived recent cognition

    Measured: 3 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2020
  2. Study start3 Oct 2022
  3. Primary completion14 Apr 2026
  4. Study completion31 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The RETURN-III study will randomize medical and surgical ICU survivors to either 12-weeks of intervention using Computerized Cognitive Rehabilitation (CCR), or control of non-specific computer games.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
160 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04353804
Sponsor's protocol ID
D2992-R
Other IDs
1506673-1, I01RX002992-01A2, 230960
Acronym
RETURN-III
Status last verified
Jun 2026
First submitted
16 Apr 2020
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The investigators will share data de-identified after study publication in accordance to clinical trial best practices and complying with federal guidelines for research.

Publications

  • Rolfsen ML, Murphy TJ, Birdrow CI, Raman R, Mastalerz NA, Wurtz MJ, Lee J, Thompson J, Mart MF, Rivera EL, Nordness MF, Collar EM, Kiehl A, Trindade AJ, Dragnich A, Qian ET, Greevy RA Jr, Jackson JC, Ely EW, Patel MB. Protocol for a multicentre, randomised controlled trial of computerised cognitive rehabilitation in survivors of critical illness: the RETURN-III study. BMJ Open. 2026 Aug 19;16(8):e118830. doi: 10.1136/bmjopen-2026-118830.

    PubMed 42624606

Questions about this trial

What is this clinical trial studying?

A study testing Treatment Arm: Computerized Cognitive Rehabilitation in people with Cognitive Rehabilitation and ICU Survivorship, run by VA Office of Research and Development at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Global Cognitive Composite Score (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04353804, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.

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