Muscle Recovery After Critical Illness

Critical Illness Clinical Trial

— TRACER-RECOVER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05537298
• Other study ID #: 77407
• Secondary ID: 5K23AR079583R01A
• Status: Recruiting
• Start date: October 18, 2022
• Est. completion date: August 1, 2027

Study information

• Verified date: June 2024
• Source: University of Kentucky
• Contact: Kirby P Mayer, PhD
• Phone: 859-218-0596
• Email: kpmaye2[@]uky.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 206
• Est. completion date: August 1, 2027
• Est. primary completion date: July 2, 2027
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Asthenia
• Critical Illness
• ICU Acquired Weakness
• Muscle Weakness
• Post Intensive Care Unit Syndrome

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Kentucky	Lexington	Kentucky
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma

Sponsors (4)

Lead Sponsor	Collaborator
Kirby Mayer	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Oklahoma Medical Research Foundation, University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Physical function	Short Physical Performance Battery	the change from baseline to 12-months
Primary	Mitochondrial function	muscle mitochondrial respirometry	the change from baseline to 12-months
Primary	Muscle strength	lower-extremity muscle strength	the change from baseline to 12-months
Primary	Muscle power	lower-extremity muscle power (unilateral leg-press)	the change from baseline to 12-months
Secondary	Physical activity	actigraphy	the change from baseline to 12-months
Secondary	functional mobility	timed-up and go test	the change from baseline to 12-months
Secondary	Cardiopulmonary endurance / exercise capacity	6-minute walk test	the change from baseline to 12-months
Secondary	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
Secondary	Muscle morphology #1	myofiber size	the change from baseline to 12-months
Secondary	Muscle morphology #2	myofiber type	the change from baseline to 12-months