SepsisRETURNNCT07225257
Recovery of Physical Function After Critical Illness In Older Adults
An observational study of Sepsis and Acute Lung Injury(ALI), run by University of Kentucky at 1 site in United States.
Trial summary
The proposed study is a prospective, observational study assessing the recovery of muscle and physical function in patients surviving critical illness (n =150) at hospital discharge (baseline) and repeated serially. Patients will be enrolled after life-saving modalities have been weaned near hospital discharge. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Sepsis, Acute Lung Injury(ALI)
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Mar 2026to 31 Dec 2031
- Phase
- Observational
- 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 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adults with a diagnosis of acute lung injury or sepsis who have survived an Intensive Care Unit admission for at least 72 hours.
Who may be able to join
- adult patients (≥40 years of age)
- patients who have survived an ICU admission of at least 72 hours
- diagnosis of acute lung injury or sepsis are eligible.
Who cannot join
- individuals who were not ambulatory prior to ICU admission,
- not expected to survive at least 6 months,
- have a new or pre-existing brain infarct, injury, or neurological condition with deficits preventing participation in physical testing,
- have a pre-existing geriatric syndrome that were confound recovery trajectory
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Kentucky, Lexington, Kentucky 40536
Lexington, Kentucky, 40536
Doug A Long, MS, 8593231100, delong2@uky.edu
Kirby P Mayer, DPT, Ph.D.
About this study
Official title: RETURN: Recovery of Physical Function After Critical Illness In Older Adults
The proposed study is a prospective, observational study assessing the recovery of muscle and physical function in patients surviving critical illness (n =150) at hospital discharge (baseline) and repeated serially. Patients will be enrolled after life-saving modalities have been weaned near hospital discharge. Patients will participate in testing at baseline, 3-, 6-, 12-, and 24-months after hospital discharge. In a subset of patients (n = 18), muscle biopsies will be performed at baseline and then repeated once at either 12- or 24-months after hospital discharge.
Read the detailed description
The overarching goal of the proposed study is to determine the trajectories of physical recovery and cellular markers involved with the underlying failure to recover muscle after critical illness, while exploring which characteristics are associated with sustained physical disability. This proposal will examine muscle pathophysiology carefully aligned with physical function outcomes in order to longitudinally assess the recovery, or failed recovery, of muscle function in participants after critical illness:
Aim 1: Determine the long-term trajectory of muscle strength, physical function and ADL recovery in ICU survivors. Patients (n = 150) will participate in a battery of tests to determine muscle and physical function aligned with self-reported measures of ADLs and quality of life at hospital discharge, 3-, 6-, 12-, and 24-months post.
Aim 2: Assess cellular changes in skeletal muscle in ICU survivors contributing to long-term physical dysfunction. In a subgroup of patients enrolled in Aim 1, muscle biopsies will be collected at baseline and long-term follow-up to determine oxidative stress, mitochondrial function, and cellular senescence.
- Conditions
- Sepsis, Acute Lung Injury(ALI)
- Keywords
- sepsis, acute respiratory failure, intensive care unit, Acquired muscle weakness
- Medical subject headings
- Sepsis, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| RETURN | Survivors of critical illness |
What is being measured
The primary outcome is the main question the study is designed to answer.
Muscle Strength measured by Chair Rise Test
Performance on 5x sit to stand test will be the primary outcome measure representing lower extremity muscle strength ; measured as time in seconds to complete 5 repetitive sit-stands.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Functional Capacity
The 6-minute walk test (6MWT), which measures the distance a participant can walk in six minutes and serves as an indicator of cardiopulmonary function, will be used as a primary outcome.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Secondary outcomes (13)
Muscle morphology # 1
Myofiber size
Measured: Percent change from baseline to 12 months
Muscle morphology #2
Myofiber type
Measured: Percent change from baseline to 12 months
Lower-extremity Muscle Power
Muscular Power: Power will be assessed using a linear potentiometer (HUMAC-360, CSMi, Stoughton, MA) to record the velocity and peak-velocity of a functional movement using a Shuttle MiniPress (Shuttle Systems, Bellingham, WA) as hamstring/gluteal pressdown. Outcome measure is Watts.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Muscle Size and Quality measured by Ultrasound
Ultrasound imaging will be performed to acquire images of quadriceps and tibialis anterior to measure muscle cross-sectional area, muscle thickness and echo intensity of muscles.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Activities of Daily Living (ADL)
Katz ADL will be used to assess ADL. The range of scores are 0 - 6 with a higher score being an better outcome.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Health Reported Quality of Life
5 Dimension Euro-Quality of Life (EQ-5D) is a self-report instrument including 5 questions and a visual analog scale (0-100) used to measure subjective quality of life with a higher score being a better outcome.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Fatigue
The Functional Assessment of Chronic Illness Therapy (FACIT-fatigue instrument) will be used to measure subjective fatigue and quality of life. All items are summed to create a single score with a range from 0 to 52. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning and a higher quality of life.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Physical Frailty
Physical frailty will be quantified using Fried Frailty Phenotype with five criteria (weight loss, weakness, exhaustion, gait speed, and physical activity) and the Clinical Frailty Scale. Scoring is 0-5 with: ≥3/5 criteria met indicates frailty; 1-2/5 indicates pre-or-intermediate frailty; 0/5 indicates non-frail.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Physical Activity
Patients will wear an Actigraph (Garmin, Vivofit 4) or an Oura ring to measure the number of steps per day. The outcome measure will be average number of steps per day over a seven day period.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Muscle strength of quadriceps
Strength of quadriceps muscle will be recorded using a hand-held dynamometry, Lafayette Manual Muscle Test System Model-01165 (Lafayette Company, Lafayette, IN). Outcome is measured in kilograms.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Grip Strength
Hand grip strength will be assessed with a handgrip dynamometry (HGD), Jamar Hydraulic dynamometer (Sammons Preston Rolyan, Bolingbrook, IL, USA). Outcome is measured in kilograms (kgs).
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Physical function
The Short Physical Performance Battery (SPPB) assesses balance, repeated sit-to-stand performance, and 4-meter gait speed. Each component is scored and converted to an ordinal scale, with the total score ranging from 0 to 12.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Physical function
Timed-up and Go Test (TUG), which is a measure of mobility and fall risk requiring patients to stand from a chair and walk short-distance for time in seconds.
Measured: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2025
- Study start11 Mar 2026
- Primary completion1 Jun 2030 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Kentucky
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kirby Mayer, University of Kentucky
- Investigators
- Kirby P Mayer, DPT, Ph.D., Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07225257
- Sponsor's protocol ID
- 106867
- Acronym
- RETURN
- Status last verified
- May 2026
- First submitted
- 1 Oct 2025
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Not yet decided.
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RETURN: Recovery of Physical Function After Critical Illness In Older Adults
- ClinicalTrials.gov ID
- NCT07225257
- Acronym / sponsor ID
- RETURN / 106867
- Conditions
- Sepsis, Acute Lung Injury(ALI)
- Keywords
- sepsis, acute respiratory failure, intensive care unit, Acquired muscle weakness
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University of KentuckyUniversity, hospital or other
- Study start
- 11 Mar 2026 (actual)
- Primary completion
- 1 Jun 2030 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 6 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study is a prospective, observational study assessing the recovery of muscle and physical function in patients surviving critical illness (n =150) at hospital discharge (baseline) and repeated serially. Patients will be enrolled after life-saving modalities have been weaned near hospital discharge. Patients will participate in testing at baseline, 3-, 6-, 12-, and 24-months after hospital discharge. In a subset of patients (n = 18), muscle biopsies will be performed at baseline and then repeated once at either 12- or 24-months after hospital discharge.
Detailed description
The overarching goal of the proposed study is to determine the trajectories of physical recovery and cellular markers involved with the underlying failure to recover muscle after critical illness, while exploring which characteristics are associated with sustained physical disability. This proposal will examine muscle pathophysiology carefully aligned with physical function outcomes in order to longitudinally assess the recovery, or failed recovery, of muscle function in participants after critical illness:
Aim 1: Determine the long-term trajectory of muscle strength, physical function and ADL recovery in ICU survivors. Patients (n = 150) will participate in a battery of tests to determine muscle and physical function aligned with self-reported measures of ADLs and quality of life at hospital discharge, 3-, 6-, 12-, and 24-months post.
Aim 2: Assess cellular changes in skeletal muscle in ICU survivors contributing to long-term physical dysfunction. In a subgroup of patients enrolled in Aim 1, muscle biopsies will be collected at baseline and long-term follow-up to determine oxidative stress, mitochondrial function, and cellular senescence.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RETURN | – | –Survivors of critical illness |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with a diagnosis of acute lung injury or sepsis who have survived an Intensive Care Unit admission for at least 72 hours.
Key inclusion criteria (3 listed)
- adult patients (≥40 years of age)
- patients who have survived an ICU admission of at least 72 hours
- diagnosis of acute lung injury or sepsis are eligible.
Key exclusion criteria (4 listed)
- individuals who were not ambulatory prior to ICU admission,
- not expected to survive at least 6 months,
- have a new or pre-existing brain infarct, injury, or neurological condition with deficits preventing participation in physical testing,
- have a pre-existing geriatric syndrome that were confound recovery trajectory
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Muscle Strength measured by Chair Rise Test
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Performance on 5x sit to stand test will be the primary outcome measure representing lower extremity muscle strength ; measured as time in seconds to complete 5 repetitive sit-stands.
Functional Capacity
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
The 6-minute walk test (6MWT), which measures the distance a participant can walk in six minutes and serves as an indicator of cardiopulmonary function, will be used as a primary outcome.
13 secondary outcomes
Muscle morphology # 1
Time frame: Percent change from baseline to 12 months
Muscle morphology #2
Time frame: Percent change from baseline to 12 months
Lower-extremity Muscle Power
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Muscle Size and Quality measured by Ultrasound
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Activities of Daily Living (ADL)
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Health Reported Quality of Life
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Fatigue
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Physical Frailty
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Physical Activity
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Muscle strength of quadriceps
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Grip Strength
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Physical function
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Physical function
Time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Individual participant dataSharing planned: Undecided. Not yet decided.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kirby P Mayer, DPT, Ph.D. principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Acute Lung Injury(ALI), run by University of Kentucky at 1 site 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 3 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Contact Doug Long, MS (859-218-0596, delong2@uky.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscle Strength measured by Chair Rise Test (time frame: Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 May 2026.