Critical Illness Myopathy and Trajectory of Recovery in AKI Requiring CRRT

Acute Kidney Injury Clinical Trial

Official title:

Critical Illness Myopathy and Trajectory of Recovery in Acute Kidney Injury (AKI) Requiring Continuous Renal Replacement Therapy (CRRT): A Prospective Observational Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05287204
• Other study ID #: 202002328
• Status: Active, not recruiting
• Start date: November 29, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: March 2024
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

Acute kidney injury (AKI), the abrupt loss of kidney function, is a common complication that affects more than half of all intensive care unit (ICU) admissions, and it is associated with substantially higher rates of morbidity and mortality in both the short- and the long-term. This is especially true in patients with AKI requiring renal replacement therapy (AKI-RRT), also known as dialysis. An understudied mechanism by which AKI-RRT may contribute to poor clinical outcomes, both in the hospital and after discharge, is through its impact on muscle mass and muscle function. AKI of any severity is known to alter tissue utilization of amino acids, and preliminary data suggest that RRT in the ICU may exacerbate muscle dysfunction through the removal of large quantities of amino acids from the patient's plasma. This study will determine whether patients with AKI-RRT have greater lean muscle loss over 1 week than historical critically ill controls, whether patients with AKI-RRT have diminished recovery of muscle mass and function at 1-3 months following discharge compared to controls, and whether changes in plasma levels of amino acids during hospitalization correlate with loss of muscle function or lack of recovery.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: December 30, 2024
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

• >18 years old

• AKI requiring CRRT, with enrollment within 48 hours of CRRT initiation

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Critical Illness
• Critical Illness Myopathy
• Dialysis; Complications
• Muscular Diseases

Intervention

Diagnostic Test:
• Musculoskeletal ultrasound
Ultrasound of rectus femoris to determine cross-sectional area, muscle thickness, echo intensity.
• Assessments of muscle strength and physical function
A battery of tests of physical function and muscle strength (see outcomes section for details).
• Metabolomics
Using metabolomic analysis, concentrations of amino acids and other important analytes will be measured in patient plasma and CRRT effluent

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	University of Iowa	Iowa City	Iowa
United States	University of Kentucky	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
University of Iowa

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	RF CSA at discharge	RF CSA as assessed by MSKUS will be measured at hospital discharge.	1 month
Primary	RF mT at discharge	RF mT as assessed by MSKUS will be measured at hospital discharge.	1 month
Primary	RF EI at discharge	RF EI as assessed by MSKUS will be measured at hospital discharge.	1 month
Primary	RF CSA at post-discharge outpatient visit	RF CSA as assessed by MSKUS will be measured at outpatient follow-up visit.	1-3 months
Primary	RF mT at post-discharge outpatient visit	RF mT as assessed by MSKUS will be measured at outpatient follow-up visit.	1-3 months
Primary	RF EI at post-discharge outpatient visit	RF mT as assessed by MSKUS will be measured at outpatient follow-up visit.	1-3 months
Primary	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
Primary	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
Primary	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
Primary	Muscle Strength - knee extension by hand-held dynamometry (HHD) at hospital discharge	Maximal isometric knee extensor muscle strength as measured by HHD.	1 month
Primary	Muscle Strength - knee extension by HHD at post-discharge outpatient visit	Maximal isometric knee extensor muscle strength as measured by HHD.	1-3 months
Primary	Muscle Strength - Grip Strength at hospital discharge	Maximal isometric grip strength as measured by hand-grip dynamometry (HGD)	1 month
Primary	Muscle Strength - Grip Strength at post-discharge outpatient visit	Maximal isometric grip strength as measured by HGD	1-3 months
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Return to driving	Yes / No outcome assessed at the outpatient follow-up visit	1-3 months
Primary	Return to work or hobby	Yes / No outcome assessed at the outpatient follow-up visit	1-3 months
Primary	Hospital Readmission	Yes / No outcome assessed at the outpatient follow-up visit	1-3 months
Primary	Emergency Department Visit	Yes / No outcome assessed at the outpatient follow-up visit	1-3 months
Secondary	ICU Stage: Changes in Plasma Metabolome	Plasma samples will be obtained 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) and metabolomic analysis will be performed to determine if changes in the plasma metabolome with CRRT initiation correlate with parameters of muscle wasting and/or trajectory of recovery of muscle weakness.	7 days
Secondary	ICU Stage: Changes in CRRT Effluent Metabolome	CRRT effluent samples will be obtained 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) and metabolomic analysis will be performed to determine if changes in the effluent metabolome with CRRT initiation correlate with parameters of muscle wasting and/or trajectory of recovery of muscle weakness.	7 days