Muscle Recovery After Critical Illness (TRACER)

Cellular and Physical Function Outcomes Leading to Failed Muscle Recovery After Critical Illness/Muscle and Physical Functional Recovery After Acute Critical Illness

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:

1. to examine the recovery of muscle and physical function in ICU survivors through longitudinal assessments
2. to investigate the underlying cellular markers and mechanisms of muscle recovery in ICU survivors
3. to determine which cellular markers contribute to physical disability in ICU survivors up to 1 year after hospital admission

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Muscle Weakness; ICU Acquired Weakness; Post Intensive Care Unit Syndrome

Detailed Description

Patients surviving critical illness develop significant impairments in skeletal muscle, commonly referred to as ICU-acquired weakness (ICUAW)[8-10]. It is estimated that up to 70-80% of patients admitted to ICU will develop some degree of neuromuscular dysfunction, weakness, myopathy or atrophy [11,12]. ICUAW encompasses muscle impairments that develop as a direct result of admission for critical illness[13] and is an independent predictor of mortality and long-term functional impairments[14-19]. Interventions to mitigate muscle deficits and improve physical function are a critical area of rehabilitation because of the high prevalence of short- and long-term impairments. ICU survivorship is particularly important as roughly 6 million Americans will survive an acute admission to the ICU this year alone.[24-26] Survivors of critical illnesses such as sepsis, viral-illnesses including coronaviruses, and acute respiratory failure (ARF) have reduced quality of life, lost wages from inability to return to work and increased caregiver and healthcare burden for years after hospital discharge.[27-31] Impairments in skeletal muscle are known contributors to physical disability and specifically prevent the performance of simple daily life activities like standing up from a chair. However, very little is known about cellular mechanisms leading to muscle and physical dysfunction in patients surviving critical illness during recovery. These gaps in knowledge are significant because identifying the phenotypes and underlying cellular mechanisms that lead to impaired muscle and physical function will facilitate the development of pharmacologic and non-pharmacologic interventions to mitigate or reverse disability. From a scientific perspective, this proposal is noteworthy because it will be the first to assess muscle protein synthesis rates in combination with cellular phenotypes, muscle strength, and physical function in patients recovering from an ICU admission. Studying muscle at the cellular level and integrating that knowledge with physical function will help improve our understanding of why certain patients fail to recover.

Elucidating cellular mechanisms during recovery phase will provide the framework to develop interventions in subsequent studies. We will assess measures of muscle and physical function in the first year of recovery to establish why some patients have restored function, yet others have sustained disability. Improved classification of muscle dysfunction and physical function enables future studies to employ a targeted approach instead of the historical rehabilitation approach of one-size-fits-all. Specifically, the cellular findings will lead to development of novel interventions specifically designed for the underlying mechanisms, while identification of the recovery trajectories will enhance clinicians' ability to implement interventions to patients with the greatest need.

• Study Type: Observational
• Enrollment (Estimated): 209

Contacts and Locations

• Study Contact: Name: Doug Long, MS; Phone Number: 859-32-5438; Email: delong2@uky.edu
• Study Contact Backup: Name: Kirby P Mayer, PhD; Phone Number: 859-218-0596; Email: kpmaye2@uky.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35005
      • Active, not recruiting
      • University of Alabama at Birmingham
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky
      • Principal Investigator: Esther E Dupont-Versteegden, PhD
      • Sub-Investigator: Ashley A Montgomery-Yates, MD
      • Sub-Investigator: Anna G. Kalema, MD
      • Sub-Investigator: Jamie L Sturgill, PhD
      • Sub-Investigator: Philip Kern, MD
      • Contact: Kirby Mayer, DPT, PhD; Phone Number: 8593233863; Email: kpmaye2@uky.edu
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73113
      • Active, not recruiting
      • Oklahoma Medical Research Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to ICU for critical illness and expected to survive

Description

Inclusion Criteria:

• adult (>18 y/o)
• admission for sepsis or acute respiratory failure with at least 72 hour stay in ICU

Exclusion Criteria:

• patients who were not ambulatory prior to ICU admission
• experienced >2 ICU admissions in the past year (chronic or recurrent critical illness due to the same or different reason
• patients not expected to survive ~6months after admission
• acute or chronic neurologic condition
• acute or chronic orthopedic condition preventing strength/functional testing
• morbid obesity >50 kg/m2 due to distortion of muscle ultrasonography

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Control; A group of healthy controls will be recruited to serve as comparator to measures of strength, power, physical function, and muscle tissue analyses. Controls will participate in a one-time assessment.
Survivor; Patients (n = 209) surviving critical illness will be enrolled to longitudinal, observational study examining muscle strength, power, and fatigue as well as physical function at hospital discharge and repeated at 3-, 6-, and 12-month following. A subset of individuals (n =32) will undergo muscle biopsies and blood will be collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical function	Short Physical Performance Battery	the change from baseline to 12-months
Mitochondrial function	muscle mitochondrial respirometry	the change from baseline to 12-months
Muscle power	lower-extremity muscle power (unilateral leg-press to record Watts)	the change from baseline to 12-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiopulmonary endurance / exercise capacity	6-minute walk test	the change from baseline to 12-months
self-reported health-related quality of life	EuroQol-5Domains (EQ-5D) visual analog scale is a self-report of quality of life (0-100) with higher scores indicating a better perception of quality of life	the change from baseline to 12-months
Muscle morphology #1	myofiber size	the change from baseline to 12-months
Muscle morphology #2	myofiber type	the change from baseline to 12-months
Physical activity	actigraphy measuring steps per day	the change from baseline to 12-months
Functional mobility	timed-up and go test	the change from baseline to 12-months
Muscle strength	lower-extremity muscle strength measured by hand-held dynamometry (kilogram of force)	the change from baseline to 12-months

Collaborators and Investigators

• Sponsor: Esther Dupont-Versteegden
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); University of Alabama at Birmingham; Oklahoma Medical Research Foundation
• Investigators: Study Director: Kirby P Mayer, PhD, University of Kentucky

Publications and helpful links

General Publications

• Gonzalez-Seguel F, Summers LA, Fresenko LE, Long DE, Scott LN, Slone SA, Shankara Bhaktula S, Wen Y, Miller BF, Morris PE, Salyer AL, Kalema AG, Montgomery-Yates AA, Dupont-Versteegden EE, Mayer KP; TRACER study group Collaborators. Trajectories of Recovery after ACutE and cRitical illness (TRACER): a prospective observational study protocol. BMJ Open. 2025 Nov 19;15(11):e108885. doi: 10.1136/bmjopen-2025-108885.

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2022
• Primary Completion (Estimated): July 2, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: July 27, 2022
• First Submitted That Met QC Criteria: September 8, 2022
• First Posted (Actual): September 13, 2022

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: physical function; skeletal muscle
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Critical Illness; Muscle Weakness
• Other Study ID Numbers: 77407; 5K23AR079583 (U.S. NIH Grant/Contract); R01AR081002 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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