Defining the Mechanisms Underlying Adrenal Insufficiency in Cirrhosis

December 10, 2023 updated by: Brian Wentworth, MD, University of Virginia

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

Active, not recruiting

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

76

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 Locations

    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia Health System
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Helmy Siragy, MD
        • Sub-Investigator:
          • Stephen Caldwell, MD
        • Sub-Investigator:
          • Curtis Argo, MD

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

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

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

Secondary Outcome Measures

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

Collaborators and Investigators

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

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)

August 2, 2021

Primary Completion (Actual)

June 30, 2023

Study Completion (Estimated)

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 18, 2023

Last Update Submitted That Met QC Criteria

December 10, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

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

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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