Critical Illness Myopathy and Trajectory of Recovery in AKI Requiring CRRT

March 27, 2024 updated by: Benjamin Griffin, University of Iowa

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Kentucky
      • Lexington, Kentucky, United States, 40506
        • University of Kentucky
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
AKI-RRT
Adults admitted to the ICU with AKI requiring CRRT with study enrollment within 48 hours of CRRT initiation.
Diagnostic test: Musculoskeletal ultrasound
Ultrasound of rectus femoris to determine cross-sectional area, muscle thickness, echo intensity.
Diagnostic test: Assessments of muscle strength and physical function
A battery of tests of physical function and muscle strength (see outcomes section for details).
Diagnostic test: Metabolomics
Using metabolomic analysis, concentrations of amino acids and other important analytes will be measured in patient plasma and CRRT effluent
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
Ultrasound of rectus femoris to determine cross-sectional area, muscle thickness, echo intensity.
Diagnostic test: Assessments of muscle strength and physical function
A battery of tests of physical function and muscle strength (see outcomes section for details).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
ICU Stage: rectus femoris (RF) cross-sectional area (CSA)
Time Frame: 7 days
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)
Time Frame: 7 days
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)
Time Frame: 7 days
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
Time Frame: 1 month
RF CSA as assessed by MSKUS will be measured at hospital discharge.
1 month
RF mT at discharge
Time Frame: 1 month
RF mT as assessed by MSKUS will be measured at hospital discharge.
1 month
RF EI at discharge
Time Frame: 1 month
RF EI as assessed by MSKUS will be measured at hospital discharge.
1 month
RF CSA at post-discharge outpatient visit
Time Frame: 1-3 months
RF CSA as assessed by MSKUS will be measured at outpatient follow-up visit.
1-3 months
RF mT at post-discharge outpatient visit
Time Frame: 1-3 months
RF mT as assessed by MSKUS will be measured at outpatient follow-up visit.
1-3 months
RF EI at post-discharge outpatient visit
Time Frame: 1-3 months
RF mT as assessed by MSKUS will be measured at outpatient follow-up visit.
1-3 months
ICU Stage: ICU Mobility Scale
Time Frame: 7 days
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
Time Frame: 1 month
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
Time Frame: 1-3 months
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
Time Frame: 1 month
Maximal isometric knee extensor muscle strength as measured by HHD.
1 month
Muscle Strength - knee extension by HHD at post-discharge outpatient visit
Time Frame: 1-3 months
Maximal isometric knee extensor muscle strength as measured by HHD.
1-3 months
Muscle Strength - Grip Strength at hospital discharge
Time Frame: 1 month
Maximal isometric grip strength as measured by hand-grip dynamometry (HGD)
1 month
Muscle Strength - Grip Strength at post-discharge outpatient visit
Time Frame: 1-3 months
Maximal isometric grip strength as measured by HGD
1-3 months
Physical Function - Short Physical Performance Battery (SPPB) at discharge
Time Frame: 1 month
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
Time Frame: 1-3 months
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
Time Frame: 1-3 months
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
Time Frame: 1-3 months
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
Time Frame: 1-3 months
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
Time Frame: 1-3 months
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
Time Frame: 1-3 months
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
Time Frame: 1-3 months
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
Time Frame: 1-3 months
Yes / No outcome assessed at the outpatient follow-up visit
1-3 months
Return to work or hobby
Time Frame: 1-3 months
Yes / No outcome assessed at the outpatient follow-up visit
1-3 months
Hospital Readmission
Time Frame: 1-3 months
Yes / No outcome assessed at the outpatient follow-up visit
1-3 months
Emergency Department Visit
Time Frame: 1-3 months
Yes / No outcome assessed at the outpatient follow-up visit
1-3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
ICU Stage: Changes in Plasma Metabolome
Time Frame: 7 days
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
ICU Stage: Changes in CRRT Effluent Metabolome
Time Frame: 7 days
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Iowa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 29, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 20, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 18, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 28, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202002328

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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