Ignite Creation Date:
2024-10-25 @ 7:49 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06593015
Status:
COMPLETED
Last Update Posted:
None
First Post:
2024-09-04
Brief Title:
Protocol for Muscle Attenuation Cut-offs in Cirrhosis
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Study Protocol to Redefine Muscle Attenuation Cut-offs for Better Prediction of Mortality in Patients with Cirrhosis a Comprehensive Post-hoc Validation Study
Status:
COMPLETED
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Myocirrhosis
Brief Summary:
The goal of this observational study is to learn if new muscle attenuation cut-offs for the definition of myosteatosis can better predict survival in patients with cirrhosis The main questions it aims to answer are
Can these new muscle attenuation cut-offs more accurately diagnose myosteatosis fat infiltration in muscle mass in cirrhosis
Do these cut-offs work effectively across different patient groups including men and women those with obesity and those with fluid retention in the abdomen
Researchers will compare patients with cirrhosis from a retrospective Canadian cohort to those from a prospective Italian cohort to see if the new cut-offs predict survival better than existing ones
Due to the retrospective nature of the study no action is required from participants
Can these new muscle attenuation cut-offs more accurately diagnose myosteatosis fat infiltration in muscle mass in cirrhosis
Do these cut-offs work effectively across different patient groups including men and women those with obesity and those with fluid retention in the abdomen
Researchers will compare patients with cirrhosis from a retrospective Canadian cohort to those from a prospective Italian cohort to see if the new cut-offs predict survival better than existing ones
Due to the retrospective nature of the study no action is required from participants
Detailed Description:
Detailed Description This observational study seeks to redefine muscle attenuation cut-offs to better predict mortality in patients with cirrhosis particularly focusing on myosteatosis-a condition characterized by the pathological accumulation of fat within skeletal muscles Myosteatosis is a critical factor in cirrhosis associated with poor outcomes including increased risk of overt hepatic encephalopathy prolonged hospitalization post-transplant complications and reduced survival The current cut-offs for diagnosing myosteatosis are derived from studies in oncology populations which may not be appropriate for cirrhosis patients due to specific complications like fluid retention ascites and differences in fat and muscle distribution between genders
Background and Rationale Cirrhosis patients often experience muscle changes due to chronic inflammation and metabolic disturbances leading to muscle fat infiltration or myosteatosis This study builds on previous research by Ebadi et al who proposed sex-specific cut-offs lt33 HU for men and lt28 HU for women for diagnosing myosteatosis based on muscle attenuation values measured via CT scans However these cut-offs were derived from a retrospective cohort and have not been validated externally There is a clear need for liver-specific cut-offs that account for the unique characteristics of cirrhosis including the impact of fluid retention on BMI and muscle attenuation measurements
Study Objectives
The primary objective is to validate new muscle mass attenuation cut-offs for the diagnosis of myosteatosis using L3 CT scan evaluations to predict survival and outcomes in patients with cirrhosis Secondary objectives include
Assessing the accuracy of these cut-offs across different patient groups eg by gender obesity status and presence of ascites
Evaluating the prognostic significance of redefined myosteatosis when combined with sarcopenia muscle wasting
Study Design
The study involves a post-hoc analysis of data from two large cohorts
1 Retrospective Cohort Canada This cohort consists of 1104 patients evaluated for liver transplantation LT at the University of Alberta Hospital between January 2000 and August 2021 After applying exclusion criteria eg absence of cirrhosis multi-organ transplantation 863 patients were included in the final analysis
2 Prospective Cohort Italy This cohort includes 447 patients from 26 Italian centers prospectively enrolled between January 2019 and January 2020 with cirrhosis who underwent abdominal CT scans After excluding patients with incomplete data 433 patients were included in the analysis
Data Collection
Data were collected at the time of enrollment and included
Demographic characteristics Age sex
Anthropometric measurements Height weight BMI
Cirrhosis etiology Hepatitis C alcohol-related liver disease non-alcoholic steatohepatitis NASH etc
Comorbidities Diabetes hypertension dyslipidemia
Liver complications Refractory ascites variceal bleeding hepatic encephalopathy hepatocellular carcinoma HCC
Liver classification and blood tests Child-Pugh score MELD score MELD-Na score albumin sodium creatinine INR bilirubin hemoglobin etc
Radiological evaluation Muscle mass and quality assessments via CT scans at the L3 or L3L4 vertebrae level including muscle attenuation and skeletal muscle index SMI
Radiological Assessment Muscle mass and attenuation were measured using CT scans with radiodensity measured in Hounsfield Units HU being the primary indicator of myosteatosis The HU thresholds for assessing skeletal muscle ranged from -29 to 150 HU The muscle area was adjusted for height to obtain the L3 or L3L4 skeletal muscle index SMI Sarcopenia was diagnosed using validated SMI cut-off values lt50 cm²m² for men and lt39 cm²m² for women The study specifically examines muscle attenuation in relation to BMI gender and ascites to refine the diagnostic criteria for myosteatosis
Patient Classification
Patients were classified into four groups based on the presence of myosteatosis and sarcopenia
1 No muscle changes No myosteatosis no sarcopenia
2 Isolated myosteatosis Myosteatosis without sarcopenia
3 Isolated sarcopenia Sarcopenia without myosteatosis
4 Combined Both myosteatosis and sarcopenia
Statistical Analysis
To validate the new cut-offs the study will
Perform univariate analyses on variables likely associated with mortality such as muscle attenuation and muscle mass
Conduct multivariate analyses to assess the impact of confounding variables
Use Receiver Operating Characteristic ROC curves stratified by sex BMI and ascites to identify the muscle attenuation values most strongly associated with mortality
Assess non-causal concordance kappa index between CT scan measurements across the two cohorts by exchanging and reanalyzing a subset of data
The study aims to confirm or refine the cut-offs proposed by Ebadi et al and evaluate their adequacy in different cirrhotic populations stratified by disease severity and history of decompensation
Follow-Up and Outcomes In the retrospective cohort patients were followed for an average of 24 35 months with outcomes such as death and liver transplantation recorded In the prospective cohort patients were followed for 12 months post-enrollment with outcomes including survival hospitalizations and liver-related complications Data from these follow-ups will be crucial in validating the predictive power of the new muscle attenuation cut-offs
Ethical Considerations
The study protocol has been reviewed and approved by the Institutional Review Board of the University of Alberta approval number Pro00066572 for the retrospective cohort and by the Ethical Committee of the Romes Center EC n 9419 300119 for the prospective cohort Each participating center provided its own ethical approval and all patients gave informed consent for their participation
Conclusion This study aims to provide a more accurate and tailored method for diagnosing myosteatosis in patients with cirrhosis by refining muscle attenuation cut-offs By validating these new thresholds the study hopes to improve the prediction of patient outcomes and aid in the management and treatment strategies for cirrhosis ultimately leading to better patient care and survival rates
Background and Rationale Cirrhosis patients often experience muscle changes due to chronic inflammation and metabolic disturbances leading to muscle fat infiltration or myosteatosis This study builds on previous research by Ebadi et al who proposed sex-specific cut-offs lt33 HU for men and lt28 HU for women for diagnosing myosteatosis based on muscle attenuation values measured via CT scans However these cut-offs were derived from a retrospective cohort and have not been validated externally There is a clear need for liver-specific cut-offs that account for the unique characteristics of cirrhosis including the impact of fluid retention on BMI and muscle attenuation measurements
Study Objectives
The primary objective is to validate new muscle mass attenuation cut-offs for the diagnosis of myosteatosis using L3 CT scan evaluations to predict survival and outcomes in patients with cirrhosis Secondary objectives include
Assessing the accuracy of these cut-offs across different patient groups eg by gender obesity status and presence of ascites
Evaluating the prognostic significance of redefined myosteatosis when combined with sarcopenia muscle wasting
Study Design
The study involves a post-hoc analysis of data from two large cohorts
1 Retrospective Cohort Canada This cohort consists of 1104 patients evaluated for liver transplantation LT at the University of Alberta Hospital between January 2000 and August 2021 After applying exclusion criteria eg absence of cirrhosis multi-organ transplantation 863 patients were included in the final analysis
2 Prospective Cohort Italy This cohort includes 447 patients from 26 Italian centers prospectively enrolled between January 2019 and January 2020 with cirrhosis who underwent abdominal CT scans After excluding patients with incomplete data 433 patients were included in the analysis
Data Collection
Data were collected at the time of enrollment and included
Demographic characteristics Age sex
Anthropometric measurements Height weight BMI
Cirrhosis etiology Hepatitis C alcohol-related liver disease non-alcoholic steatohepatitis NASH etc
Comorbidities Diabetes hypertension dyslipidemia
Liver complications Refractory ascites variceal bleeding hepatic encephalopathy hepatocellular carcinoma HCC
Liver classification and blood tests Child-Pugh score MELD score MELD-Na score albumin sodium creatinine INR bilirubin hemoglobin etc
Radiological evaluation Muscle mass and quality assessments via CT scans at the L3 or L3L4 vertebrae level including muscle attenuation and skeletal muscle index SMI
Radiological Assessment Muscle mass and attenuation were measured using CT scans with radiodensity measured in Hounsfield Units HU being the primary indicator of myosteatosis The HU thresholds for assessing skeletal muscle ranged from -29 to 150 HU The muscle area was adjusted for height to obtain the L3 or L3L4 skeletal muscle index SMI Sarcopenia was diagnosed using validated SMI cut-off values lt50 cm²m² for men and lt39 cm²m² for women The study specifically examines muscle attenuation in relation to BMI gender and ascites to refine the diagnostic criteria for myosteatosis
Patient Classification
Patients were classified into four groups based on the presence of myosteatosis and sarcopenia
1 No muscle changes No myosteatosis no sarcopenia
2 Isolated myosteatosis Myosteatosis without sarcopenia
3 Isolated sarcopenia Sarcopenia without myosteatosis
4 Combined Both myosteatosis and sarcopenia
Statistical Analysis
To validate the new cut-offs the study will
Perform univariate analyses on variables likely associated with mortality such as muscle attenuation and muscle mass
Conduct multivariate analyses to assess the impact of confounding variables
Use Receiver Operating Characteristic ROC curves stratified by sex BMI and ascites to identify the muscle attenuation values most strongly associated with mortality
Assess non-causal concordance kappa index between CT scan measurements across the two cohorts by exchanging and reanalyzing a subset of data
The study aims to confirm or refine the cut-offs proposed by Ebadi et al and evaluate their adequacy in different cirrhotic populations stratified by disease severity and history of decompensation
Follow-Up and Outcomes In the retrospective cohort patients were followed for an average of 24 35 months with outcomes such as death and liver transplantation recorded In the prospective cohort patients were followed for 12 months post-enrollment with outcomes including survival hospitalizations and liver-related complications Data from these follow-ups will be crucial in validating the predictive power of the new muscle attenuation cut-offs
Ethical Considerations
The study protocol has been reviewed and approved by the Institutional Review Board of the University of Alberta approval number Pro00066572 for the retrospective cohort and by the Ethical Committee of the Romes Center EC n 9419 300119 for the prospective cohort Each participating center provided its own ethical approval and all patients gave informed consent for their participation
Conclusion This study aims to provide a more accurate and tailored method for diagnosing myosteatosis in patients with cirrhosis by refining muscle attenuation cut-offs By validating these new thresholds the study hopes to improve the prediction of patient outcomes and aid in the management and treatment strategies for cirrhosis ultimately leading to better patient care and survival rates
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None