Recovery of Physical Function After Critical Illness In Older Adults (RETURN)

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.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Acute Lung Injury(ALI)

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 Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Doug Long, MS; Phone Number: 859-218-0596; Email: delong2@uky.edu
• Study Contact Backup: Name: Kirby P Mayer, DPT, Ph.D.; Phone Number: 859-218-0596; Email: kpmaye2@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky, Lexington, Kentucky 40536
      • Principal Investigator: Kirby P Mayer, DPT, Ph.D.
      • Sub-Investigator: Esther Dupont-Versteegden, Ph.D.
      • Contact: Doug A Long, MS; Phone Number: 8593231100; Email: delong2@uky.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

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.

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
RETURN; Survivors of critical illness

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle morphology # 1	Myofiber size	Percent change from baseline to 12 months
Muscle morphology #2	Myofiber type	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.	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.	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.	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.	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.	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.	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.	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.	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).	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.	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.	Baseline and repeated 3-, 6-, 12-, and 24-months after baseline assessment.

Collaborators and Investigators

• Sponsor: University of Kentucky
• Investigators: Principal Investigator: Kirby P Mayer, DPT, Ph.D., University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: October 1, 2025
• First Submitted That Met QC Criteria: November 5, 2025
• First Posted (Actual): November 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: intensive care unit; sepsis; acute respiratory failure; Acquired muscle weakness
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Lung Diseases; Lung Injury; Pathological Conditions, Signs and Symptoms; Sepsis; Acute Lung Injury
• Other Study ID Numbers: 106867

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Not yet decided.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No