Defining the Mechanisms Underlying Adrenal Insufficiency in Cirrhosis

NCT04642391 | Completed FDA Drug

• 1 other identifier: HSR200392
• Study Type: observational
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cirrhosis; Adrenal Insufficiency

Outcome Measures

Primary Outcomes (56)

• 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 Outcomes (16)

• 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

Study Arms (2)

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

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

Interventions

Cosyntropin DRUG

Administer 0.25mg Cosyntropin to determine adrenal sufficiency vs. insufficiency in patients with decompensated cirrhosis

Non-RAI; RAI

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Virginia: lead
• American Association for the Study of Liver Diseases: collaborator

Study Sites (1)

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Human serum and plasma

MeSH Terms

Conditions

Fibrosis; Adrenal Insufficiency

Interventions

Cosyntropin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Adrenocorticotropic Hormone; Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Medicine

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 24, 2020
• Study Start: August 2, 2021
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)