Muscle Recovery After Critical Illness

NCT ID: NCT05537298

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 209 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-10-18
• Study Completion Date: 2027-08-01

Brief Summary

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

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.

Conditions

ICU Acquired Weakness; Post Intensive Care Unit Syndrome; Muscle Weakness; Critical Illness

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• acute or chronic neurologic condition
• acute or chronic orthopedic condition preventing strength/functional testing
• patients who were not ambulatory prior to ICU admission
• patients not expected to survive ~6months after admission

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Oklahoma Medical Research Foundation

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

Kirby Mayer

OTHER

Sponsor Role: lead

Responsible Party

Kirby Mayer

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kirby P Mayer, PhD

Role: STUDY_DIRECTOR

University of Kentucky

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status: ACTIVE_NOT_RECRUITING

University of Kentucky

Lexington, Kentucky, United States

Site Status: RECRUITING

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States

Central Contacts

Kirby P Mayer, PhD

Role: CONTACT

kpmaye2@uky.edu

859-218-0596

Doug Long, MS

Role: CONTACT

delong2@uky.edu

859-32-5438

Facility Contacts

Kirby Mayer, DPT, PhD

Role: primary

kpmaye2@uky.edu

8593233863

References

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.

Reference Type: DERIVED

PMID: 41263932 (View on PubMed)

Other Identifiers

5K23AR079583

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01AR081002

Identifier Type: NIH

Identifier Source: secondary_id

View Link

77407

Identifier Type: -

Identifier Source: org_study_id