Clinical trial NCT04642391: Defining the Mechanisms Underlying Adrenal Insufficiency in Cirrhosis
Official title: Defining the Mechanisms Underlying Adrenal Dysfunction in Cirrhosis and Its Prognostic Significance
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cirrhosis
Adrenal Insufficiency
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: American Association for the Study of Liver Diseases
First posted: 2020-11-24
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

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.


Eligibility criteria: 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

Primary outcomes:
measure: RAI prevalence
timeFrame: 1 year
measure: Baseline Cholesterol Esterification Percentage
timeFrame: baseline
measure: 6 month Cholesterol Esterification Percentage
timeFrame: 6 months
measure: 12 month Cholesterol Esterification Percentage
timeFrame: 12 months
measure: 18 month Cholesterol Esterification Percentage
timeFrame: 18 months
measure: 24 month Cholesterol Esterification Percentage
timeFrame: 24 months
measure: Baseline 17-OH Progesterone Level
timeFrame: baseline
measure: 6 month 17-OH Progesterone Level
timeFrame: 6 month
measure: 12 month 17-OH Progesterone Level
timeFrame: 12 months
measure: 18 month 17-OH Progesterone Level
timeFrame: 18 months
measure: 24 month 17-OH Progesterone Level
timeFrame: 24 months
measure: Baseline ACTH level
timeFrame: baseline
measure: 6 month ACTH level
timeFrame: 6 months
measure: 12 month ACTH level
timeFrame: 12 months
measure: 18 month ACTH level
timeFrame: 18 months
measure: 24 month ACTH level
timeFrame: 24 months
measure: Baseline IL-1 Level
timeFrame: baseline
measure: 6 month IL-1 Level
timeFrame: 6 months
measure: 12 month IL-1 Level
timeFrame: 12 months
measure: 18 month IL-1 Level
timeFrame: 18 months
measure: 24 month IL-1 Level
timeFrame: 24 months
measure: Baseline Plasma Renin Activity
timeFrame: baseline
measure: 6 month Plasma Renin Activity
timeFrame: 6 month
measure: 12 month Plasma Renin Activity
timeFrame: 12 month
measure: 18 month Plasma Renin Activity
timeFrame: 18 month
measure: 24 month Plasma Renin Activity
timeFrame: 24 month
measure: Baseline serum normetanephrine level
timeFrame: baseline
measure: 6 month serum normetanephrine level
timeFrame: 6 month
measure: 12 month serum normetanephrine level
timeFrame: 12 month
measure: 18 month serum normetanephrine level
timeFrame: 18 month
measure: 24 month serum normetanephrine level
timeFrame: 24 month
measure: Baseline 11-deoxycortisol level
timeFrame: baseline
measure: 6 month 11-deoxycortisol level
timeFrame: 6 months
measure: 12 month 11-deoxycortisol level
timeFrame: 12 months
measure: 18 month 11-deoxycortisol level
timeFrame: 18 months
measure: 24 month 11-deoxycortisol level
timeFrame: 24 months
measure: Baseline HDL level
timeFrame: baseline
measure: 6 month HDL level
timeFrame: 6 months
measure: 12 month HDL level
timeFrame: 12 months
measure: 18 month HDL level
timeFrame: 18 months
measure: 24 month HDL level
timeFrame: 24 months
measure: Baseline IL-6 level
timeFrame: baseline
measure: 6 month IL-6 level
timeFrame: 6 months
measure: 12 month IL-6 level
timeFrame: 12 months
measure: 18 month IL-6 level
timeFrame: 18 months
measure: 24 month IL-6 level
timeFrame: 24 months
measure: Baseline IL-10 level
timeFrame: baseline
measure: 6 month IL-10 level
timeFrame: 6 months
measure: 12 month IL-10 level
timeFrame: 12 months
measure: 18 month IL-10 level
timeFrame: 18 months
measure: 24 month IL-10 level
timeFrame: 24 months
measure: Baseline TNFa level
timeFrame: baseline
measure: 6 month TNFa level
timeFrame: 6 months
measure: 12 month TNFa level
timeFrame: 12 months
measure: 18 month TNFa level
timeFrame: 18 months
measure: 24 month TNFa level
timeFrame: 24 months
Secondary outcomes:
measure: Annualized Incidence of RAI
timeFrame: over two years
measure: 30-day transplant-free survival
timeFrame: 30 days
measure: 90-day transplant-free survival
timeFrame: 90 days
measure: 6-month transplant-free survival
timeFrame: 6 months
measure: 1 year transplant-free survival
timeFrame: 1 year
measure: 2 year transplant-free survival
timeFrame: 2 years
measure: 30 day new or worsened portal hypertensive decompensation
timeFrame: 30 days
measure: 90 day new or worsened portal hypertensive decompensation
timeFrame: 90 days
measure: 6 month new or worsened portal hypertensive decompensation
timeFrame: 6 months
measure: 1 year new or worsened portal hypertensive decompensation
timeFrame: 1 year
measure: 2 year new or worsened portal hypertensive decompensation
timeFrame: 2 years
measure: 30 day unplanned hospitalization
timeFrame: 30 days
measure: 90 day unplanned hospitalization
timeFrame: 90 days
measure: 6 month unplanned hospitalization
timeFrame: 6 month
measure: 1 year unplanned hospitalization
timeFrame: 1 year
measure: 2 year unplanned hospitalization
timeFrame: 2 year
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
References: