Defining the Mechanisms Underlying Adrenal Insufficiency in Cirrhosis

Defining the Mechanisms Underlying Adrenal Dysfunction in Cirrhosis and Its Prognostic Significance

This study aims to define the prevalence and potential pathophysiologic mechanisms underlying relative adrenal insufficiency (RAI) in outpatients with decompensated cirrhosis. Patients will be followed prospectively for up to two years to determine incidence of RAI, whether RAI represents a permanent or dynamic physiologic state in cirrhosis, and to determine whether RAI in this setting is associated with important clinical outcomes.

Study Overview

• Status: Completed
• Conditions: Cirrhosis; Adrenal Insufficiency
• Intervention / Treatment: Drug: Cosyntropin

• Study Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Decompensated cirrhosis (cirrhosis + at least 1 clinically-significant decompensation including ascites/hepatic hydrothorax, spontaneous bacterial peritonitis, variceal bleed, hepatic encephalopathy)

Description

Inclusion Criteria:

• Age >= 18y
• Diagnosis of cirrhosis by biopsy or compatible clinical picture
• Experienced at least one portal decompensating event in the past and currently have a Child-Pugh B or C classification

Exclusion Criteria:

• Pregnant women
• Prisoners
• Not been treated with medication known to affect the adrenal axis within the past 4 weeks (oral or IV steroids, ketoconazole, etomidate)
• Hospitalized at time of enrollment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
RAI; Subjects will be diagnosed with relative adrenal insufficiency as determined by administration of a standard-dose ACTH stimulation test (0.25mg Cosyntropin) and an increase in serum total cortisol <9mcg/dL.	Drug: Cosyntropin; Administer 0.25mg Cosyntropin to determine adrenal sufficiency vs. insufficiency in patients with decompensated cirrhosis
Non-RAI; Subjects will have not have relative adrenal insufficiency as determined by administration of a standard-dose ACTH stimulation test (0.25mg Cosyntropin) and an increase in serum total cortisol >= 9mcg/dL.	Drug: Cosyntropin; Administer 0.25mg Cosyntropin to determine adrenal sufficiency vs. insufficiency in patients with decompensated cirrhosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
RAI prevalence	1 year
Baseline Cholesterol Esterification Percentage	baseline
6 month Cholesterol Esterification Percentage	6 months
12 month Cholesterol Esterification Percentage	12 months
18 month Cholesterol Esterification Percentage	18 months
24 month Cholesterol Esterification Percentage	24 months
Baseline 17-OH Progesterone Level	baseline
6 month 17-OH Progesterone Level	6 month
12 month 17-OH Progesterone Level	12 months
18 month 17-OH Progesterone Level	18 months
24 month 17-OH Progesterone Level	24 months
Baseline ACTH level	baseline
6 month ACTH level	6 months
12 month ACTH level	12 months
18 month ACTH level	18 months
24 month ACTH level	24 months
Baseline IL-1 Level	baseline
6 month IL-1 Level	6 months
12 month IL-1 Level	12 months
18 month IL-1 Level	18 months
24 month IL-1 Level	24 months
Baseline Plasma Renin Activity	baseline
6 month Plasma Renin Activity	6 month
12 month Plasma Renin Activity	12 month
18 month Plasma Renin Activity	18 month
24 month Plasma Renin Activity	24 month
Baseline serum normetanephrine level	baseline
6 month serum normetanephrine level	6 month
12 month serum normetanephrine level	12 month
18 month serum normetanephrine level	18 month
24 month serum normetanephrine level	24 month
Baseline 11-deoxycortisol level	baseline
6 month 11-deoxycortisol level	6 months
12 month 11-deoxycortisol level	12 months
18 month 11-deoxycortisol level	18 months
24 month 11-deoxycortisol level	24 months
Baseline HDL level	baseline
6 month HDL level	6 months
12 month HDL level	12 months
18 month HDL level	18 months
24 month HDL level	24 months
Baseline IL-6 level	baseline
6 month IL-6 level	6 months
12 month IL-6 level	12 months
18 month IL-6 level	18 months
24 month IL-6 level	24 months
Baseline IL-10 level	baseline
6 month IL-10 level	6 months
12 month IL-10 level	12 months
18 month IL-10 level	18 months
24 month IL-10 level	24 months
Baseline TNFa level	baseline
6 month TNFa level	6 months
12 month TNFa level	12 months
18 month TNFa level	18 months
24 month TNFa level	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Annualized Incidence of RAI	over two years
30-day transplant-free survival	30 days
90-day transplant-free survival	90 days
6-month transplant-free survival	6 months
1 year transplant-free survival	1 year
2 year transplant-free survival	2 years
30 day new or worsened portal hypertensive decompensation	30 days
90 day new or worsened portal hypertensive decompensation	90 days
6 month new or worsened portal hypertensive decompensation	6 months
1 year new or worsened portal hypertensive decompensation	1 year
2 year new or worsened portal hypertensive decompensation	2 years
30 day unplanned hospitalization	30 days
90 day unplanned hospitalization	90 days
6 month unplanned hospitalization	6 month
1 year unplanned hospitalization	1 year
2 year unplanned hospitalization	2 year

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: American Association for the Study of Liver Diseases

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 24, 2020

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Digestive System Diseases; Liver Diseases; Adrenal Gland Diseases; Fibrosis; Liver Cirrhosis; Adrenal Insufficiency; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Cosyntropin
• Other Study ID Numbers: HSR200392

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No