Critical Illness Myopathy and Trajectory of Recovery in AKI Requiring CRRT

NCT05287204 | Active Not Recruiting

• 1 other identifier: 202002328
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine whether patients with acute kidney injury requiring renal replacement therapy have a higher incidence of muscle wasting than controls and whether the course of recovery is longer compared to controls.

Conditions

Acute Kidney Injury; Critical Illness Myopathy; Dialysis; Complications

Outcome Measures

Primary Outcomes (28)

• ICU Stage: rectus femoris (RF) cross-sectional area (CSA)

  RF CSA as assessed by musculoskeletal ultrasound (MSKUS) will be measured at day 0 (study enrollment within 48 hours of CRRT initiation), at day 3, and at day 7 (or at ICU discharge if before day 7).

  7 days

• ICU Stage: RF muscle thickness (mT)

  RF mT as assessed by MSKUS will be measured at day 0 (study enrollment within 48 hours of CRRT initiation), at day 3, and at day 7 (or at ICU discharge if before day 7).

  7 days

• ICU Stage: RF echo intensity (EI)

  RF EI as assessed by MSKUS will be measured at day 0 (study enrollment within 48 hours of CRRT initiation), at day 3, and at day 7 (or at ICU discharge if before day 7).

  7 days

• RF CSA at discharge

  RF CSA as assessed by MSKUS will be measured at hospital discharge.

  1 month

• RF mT at discharge

  RF mT as assessed by MSKUS will be measured at hospital discharge.

  1 month

• RF EI at discharge

  RF EI as assessed by MSKUS will be measured at hospital discharge.

  1 month

• RF CSA at post-discharge outpatient visit

  RF CSA as assessed by MSKUS will be measured at outpatient follow-up visit.

  1-3 months

• RF mT at post-discharge outpatient visit

  RF mT as assessed by MSKUS will be measured at outpatient follow-up visit.

  1-3 months

• RF EI at post-discharge outpatient visit

  RF mT as assessed by MSKUS will be measured at outpatient follow-up visit.

  1-3 months

• ICU Stage: ICU Mobility Scale

  The ICU Mobility Scale is an 11-point scale ranging from 0-10 which involves scoring a patient's maximum level of mobility in the prior 24-hour period. The ICU Mobility Scale will be performed at the same 3 time points as the MSKUS assessments.

  7 days

• Muscle Strength - Medical Research Council Sum-score (MRC-ss) at discharge

  MRC-ss is a measure of global peripheral muscle strength that is the current clinical standard for diagnosing ICU-acquired weakness. Muscle strength is assessed by physical exam and rated on an ordinal scale (0-5) at six bilateral muscle groups: shoulder abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, and ankle dorsiflexors.

  1 month

• Muscle Strength - MRC-ss at post-discharge outpatient visit

  MRC-ss is a measure of global peripheral muscle strength that is the current clinical standard for diagnosing ICU-acquired weakness. Muscle strength is assessed by physical exam and rated on an ordinal scale (0-5) at six bilateral muscle groups: shoulder abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, and ankle dorsiflexors.

  1-3 months

• Muscle Strength - knee extension by hand-held dynamometry (HHD) at hospital discharge

  Maximal isometric knee extensor muscle strength as measured by HHD.

  1 month

• Muscle Strength - knee extension by HHD at post-discharge outpatient visit

  Maximal isometric knee extensor muscle strength as measured by HHD.

  1-3 months

• Muscle Strength - Grip Strength at hospital discharge

  Maximal isometric grip strength as measured by hand-grip dynamometry (HGD)

  1 month

• Muscle Strength - Grip Strength at post-discharge outpatient visit

  Maximal isometric grip strength as measured by HGD

  1-3 months

• Physical Function - Short Physical Performance Battery (SPPB) at discharge

  SPPB is a performance-based composite test with a total of 12 points including components of balance (side-by-side stand, semi-tandem stand, and full-tandem stand), chair-to-stand test, and 4-meter habitual gait speed used to assess physical function and physical frailty.

  1 month

• Physical Function - SPPB at post-discharge outpatient visit

  SPPB is a performance-based composite test with a total of 12 points including components of balance (side-by-side stand, semi-tandem stand, and full-tandem stand), chair-to-stand test, and 4-meter habitual gait speed used to assess physical function and physical frailty.

  1-3 months

• TUG Test at post-discharge outpatient visit

  The Timed Up and Go (TUG) test assesses the time (in seconds) for a subject to stand on command from a seated position, walk 3 meters, turn around, walk back to the chair, and sit down, thereby assessing mobility, physical function, and fall risk.

  1-3 months

• Physical Function - 6-minute walk test (6MWT) at post-discharge outpatient visit

  The 6MWT assesses the distance a subject can walk in six minutes, providing a global representation of physical function and cardiopulmonary endurance.

  1-3 months

• Quality of Life testing using EuroQol Group 5-dimension 5-level (EQ-5D-5L) questionnaire at post-discharge outpatient visit

  The EQ-5D-5L is a standardized measure of health status developed by the Euro-Qol Group to provide an assessment of health for clinical and economic appraisal.

  1-3 months

• Physical Function - Clinical Frailty Scale (CFS) at post-discharge outpatient visit

  CFS is a widely adopted judgement-based tool to screen for frailty and to broadly stratify degrees of fitness and frailty.

  1-3 months

• Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire at post-discharge outpatient visit

  The FACIT-F scale is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function.

  1-3 months

• 36-Item Short Form Health Survey Physical Function Scale (SF-36) at post-discharge outpatient visit

  The SF-36 is a 36-item patient-reported survey of health commonly used to evaluate adult patients which contains 8 domains, including a physical function scale based on 10 of the 36 items which has been shown to have high reliability.

  1-3 months

• Return to driving

  Yes / No outcome assessed at the outpatient follow-up visit

  1-3 months

• Return to work or hobby

  Yes / No outcome assessed at the outpatient follow-up visit

  1-3 months

• Hospital Readmission

  Yes / No outcome assessed at the outpatient follow-up visit

  1-3 months

• Emergency Department Visit

  Yes / No outcome assessed at the outpatient follow-up visit

  1-3 months

Secondary Outcomes (2)

• ICU Stage: Changes in Plasma Metabolome

  7 days

• ICU Stage: Changes in CRRT Effluent Metabolome

  7 days

Study Arms (2)

AKI-RRT

Adults admitted to the ICU with AKI requiring CRRT with study enrollment within 48 hours of CRRT initiation.

Diagnostic Test: Musculoskeletal ultrasound; Diagnostic Test: Assessments of muscle strength and physical function; Diagnostic Test: Metabolomics

Historical Controls

The controls for the ICU phase will be 41 critically ill adults without AKI-RRT in whom similar measurements of muscle size, quality, and function were collected in a recent prior study \[PubMed ID: 33148301\]. The controls for the recovery phase will come from an ongoing prospective observational study being performed at the University of Kentucky, which will include outpatient functional assessments performed on 200 ICU survivors (NCT05537298).

Diagnostic Test: Musculoskeletal ultrasound; Diagnostic Test: Assessments of muscle strength and physical function

Interventions

Musculoskeletal ultrasound DIAGNOSTIC_TEST

Ultrasound of rectus femoris to determine cross-sectional area, muscle thickness, echo intensity.

AKI-RRT; Historical Controls

Assessments of muscle strength and physical function DIAGNOSTIC_TEST

A battery of tests of physical function and muscle strength (see outcomes section for details).

AKI-RRT; Historical Controls

Metabolomics DIAGNOSTIC_TEST

Using metabolomic analysis, concentrations of amino acids and other important analytes will be measured in patient plasma and CRRT effluent

AKI-RRT

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will be composed of critically ill patients with acute kidney injury requiring continuous renal replacement therapy in an ICU setting.

You may qualify if:

• \>18 years old
• AKI requiring CRRT, with enrollment within 48 hours of CRRT initiation

You may not qualify if:

• ICU admission for \>7 days
• RRT of any kind at any time prior to ICU admission
• Chronic kidney disease (CKD) with estimated glomerular filtration rate \<20 mL/min/1.73 m2 as calculated by the 2021 CKD-EPI equation
• underlying muscle disorders or muscle atrophy such as quadriplegia or hemiplegia, stroke with residual motor deficits, end-stage liver disease, active alcohol use disorder, active malignancy (other than non-melanoma skin cancer) within 1 year, burns, or other baseline neuromuscular disease
• pregnancy
• concomitant use of other extracorporeal support devices such as ventricular assist devices or extracorporeal membrane oxygenation
• anticipated inability to engage in weight-bearing testing after discharge (e.g., trauma or orthopedic surgery)
• subjects will be ineligible for outpatient testing if they remain on RRT in the week prior to the research appointment

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (3)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Related Publications (8)

• Teixeira JP, Mayer KP, Griffin BR, George N, Jenkins N, Pal CA, Gonzalez-Seguel F, Neyra JA. Intensive Care Unit-Acquired Weakness in Patients With Acute Kidney Injury: A Contemporary Review. Am J Kidney Dis. 2023 Mar;81(3):336-351. doi: 10.1053/j.ajkd.2022.08.028. Epub 2022 Nov 2.

  PMID: 36332719 BACKGROUND

• Mayer KP, Thompson Bastin ML, Montgomery-Yates AA, Pastva AM, Dupont-Versteegden EE, Parry SM, Morris PE. Acute skeletal muscle wasting and dysfunction predict physical disability at hospital discharge in patients with critical illness. Crit Care. 2020 Nov 4;24(1):637. doi: 10.1186/s13054-020-03355-x.

  PMID: 33148301 BACKGROUND

• Mayer KP, Welle MM, Evans CG, Greenhill BG, Montgomery-Yates AA, Dupont-Versteegden EE, Morris PE, Parry SM. Muscle Power is Related to Physical Function in Patients Surviving Acute Respiratory Failure: A Prospective Observational Study. Am J Med Sci. 2021 Mar;361(3):310-318. doi: 10.1016/j.amjms.2020.09.018. Epub 2020 Oct 3.

  PMID: 33189316 BACKGROUND

• Mayer KP, Dhar S, Cassity E, Denham A, England J, Morris PE, Dupont-Versteegden EE. Interrater Reliability of Muscle Ultrasonography Image Acquisition by Physical Therapists in Patients Who Have or Who Survived Critical Illness. Phys Ther. 2020 Aug 31;100(9):1701-1711. doi: 10.1093/ptj/pzaa068.

  PMID: 32302406 BACKGROUND

• Mayer KP, Ortiz-Soriano VM, Kalantar A, Lambert J, Morris PE, Neyra JA. Acute kidney injury contributes to worse physical and quality of life outcomes in survivors of critical illness. BMC Nephrol. 2022 Apr 7;23(1):137. doi: 10.1186/s12882-022-02749-z.

  PMID: 35392844 BACKGROUND

• Mayer KP, Teixeira JP, Gonzalez-Seguel F, Tran VQ, Gross JM, Horikawa-Strakovsky A, Pal CA, Shareef ZT, Puffer Israel H, Wen Y, Griffin BR, Neyra JA. Acute skeletal muscle wasting in patients with acute kidney injury requiring continuous kidney replacement therapy: A prospective multicenter study. J Crit Care. 2025 Oct;89:155142. doi: 10.1016/j.jcrc.2025.155142. Epub 2025 Jun 12.

  PMID: 40513259 DERIVED

• Gonzalez-Seguel F, Tran VQ, Pal CA, Shareef ZT, Israel HP, Horikawa-Strakovsky A, Wen Y, Griffin BR, Neyra JA, Teixeira JP, Mayer KP. Inter-rater reliability of muscle ultrasonography performed by multidisciplinary novice sonographers in the evaluation of critically ill patients with acute kidney injury requiring continuous kidney replacement therapy. Ren Fail. 2025 Dec;47(1):2472990. doi: 10.1080/0886022X.2025.2472990. Epub 2025 Mar 11.

  PMID: 40069097 DERIVED

• Teixeira JP, Griffin BR, Pal CA, Gonzalez-Seguel F, Jenkins N, Jones BM, Yoshida Y, George N, Israel HP, Ghazi L, Neyra JA, Mayer KP. Critical illness myopathy and trajectory of recovery in acute kidney injury requiring continuous renal replacement therapy: a prospective observational trial protocol. BMJ Open. 2023 May 22;13(5):e072448. doi: 10.1136/bmjopen-2023-072448.

  PMID: 37217272 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples and effluent samples will be stored for metabolomic analysis.

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 20, 2021
• First Posted: March 18, 2022
• Study Start: November 29, 2021
• Primary Completion: September 30, 2023
• Study Completion: December 30, 2024
• Last Updated: March 28, 2024

Record last verified: 2024-03

Locations

US (3)