Defining the Mechanisms Underlying Adrenal Insufficiency in Cirrhosis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
Study Design
Arms and Interventions
| Arm | 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
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Virginia Health System | Charlottesville | Virginia | United States | 22903 |
Sponsors and Collaborators
- University of Virginia
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 16007