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Defining the Mechanisms Underlying Adrenal Insufficiency in Cirrhosis

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ClinicalTrials.gov Identifier: NCT04642391
Recruitment Status : Not yet recruiting
First Posted : November 24, 2020
Last Update Posted : November 24, 2020
Sponsor:
Information provided by (Responsible Party):
Brian Wentworth, MD, University of Virginia

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
Cirrhosis Adrenal Insufficiency Drug: Cosyntropin

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Study Type : Observational
Estimated Enrollment : 135 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Defining the Incidence of and Mechanisms Underlying Adrenal Insufficiency in Cirrhosis
Estimated Study Start Date : July 1, 2021
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : December 30, 2023


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




Primary Outcome Measures :
  1. RAI prevalence [ Time Frame: 1 year ]
  2. Baseline Cholesterol Esterification Percentage [ Time Frame: baseline ]
  3. 6 month Cholesterol Esterification Percentage [ Time Frame: 6 months ]
  4. 12 month Cholesterol Esterification Percentage [ Time Frame: 12 months ]
  5. 18 month Cholesterol Esterification Percentage [ Time Frame: 18 months ]
  6. 24 month Cholesterol Esterification Percentage [ Time Frame: 24 months ]
  7. Baseline 17-OH Progesterone Level [ Time Frame: baseline ]
  8. 6 month 17-OH Progesterone Level [ Time Frame: 6 month ]
  9. 12 month 17-OH Progesterone Level [ Time Frame: 12 months ]
  10. 18 month 17-OH Progesterone Level [ Time Frame: 18 months ]
  11. 24 month 17-OH Progesterone Level [ Time Frame: 24 months ]
  12. Baseline ACTH level [ Time Frame: baseline ]
  13. 6 month ACTH level [ Time Frame: 6 months ]
  14. 12 month ACTH level [ Time Frame: 12 months ]
  15. 18 month ACTH level [ Time Frame: 18 months ]
  16. 24 month ACTH level [ Time Frame: 24 months ]
  17. Baseline IL-1 Level [ Time Frame: baseline ]
  18. 6 month IL-1 Level [ Time Frame: 6 months ]
  19. 12 month IL-1 Level [ Time Frame: 12 months ]
  20. 18 month IL-1 Level [ Time Frame: 18 months ]
  21. 24 month IL-1 Level [ Time Frame: 24 months ]
  22. Baseline Plasma Renin Activity [ Time Frame: baseline ]
  23. 6 month Plasma Renin Activity [ Time Frame: 6 month ]
  24. 12 month Plasma Renin Activity [ Time Frame: 12 month ]
  25. 18 month Plasma Renin Activity [ Time Frame: 18 month ]
  26. 24 month Plasma Renin Activity [ Time Frame: 24 month ]
  27. Baseline serum normetanephrine level [ Time Frame: baseline ]
  28. 6 month serum normetanephrine level [ Time Frame: 6 month ]
  29. 12 month serum normetanephrine level [ Time Frame: 12 month ]
  30. 18 month serum normetanephrine level [ Time Frame: 18 month ]
  31. 24 month serum normetanephrine level [ Time Frame: 24 month ]
  32. Baseline 11-deoxycortisol level [ Time Frame: baseline ]
  33. 6 month 11-deoxycortisol level [ Time Frame: 6 months ]
  34. 12 month 11-deoxycortisol level [ Time Frame: 12 months ]
  35. 18 month 11-deoxycortisol level [ Time Frame: 18 months ]
  36. 24 month 11-deoxycortisol level [ Time Frame: 24 months ]
  37. Baseline HDL level [ Time Frame: baseline ]
  38. 6 month HDL level [ Time Frame: 6 months ]
  39. 12 month HDL level [ Time Frame: 12 months ]
  40. 18 month HDL level [ Time Frame: 18 months ]
  41. 24 month HDL level [ Time Frame: 24 months ]
  42. Baseline IL-6 level [ Time Frame: baseline ]
  43. 6 month IL-6 level [ Time Frame: 6 months ]
  44. 12 month IL-6 level [ Time Frame: 12 months ]
  45. 18 month IL-6 level [ Time Frame: 18 months ]
  46. 24 month IL-6 level [ Time Frame: 24 months ]
  47. Baseline IL-10 level [ Time Frame: baseline ]
  48. 6 month IL-10 level [ Time Frame: 6 months ]
  49. 12 month IL-10 level [ Time Frame: 12 months ]
  50. 18 month IL-10 level [ Time Frame: 18 months ]
  51. 24 month IL-10 level [ Time Frame: 24 months ]
  52. Baseline TNFa level [ Time Frame: baseline ]
  53. 6 month TNFa level [ Time Frame: 6 months ]
  54. 12 month TNFa level [ Time Frame: 12 months ]
  55. 18 month TNFa level [ Time Frame: 18 months ]
  56. 24 month TNFa level [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Annualized Incidence of RAI [ Time Frame: over two years ]
  2. 30-day transplant-free survival [ Time Frame: 30 days ]
  3. 90-day transplant-free survival [ Time Frame: 90 days ]
  4. 6-month transplant-free survival [ Time Frame: 6 months ]
  5. 1 year transplant-free survival [ Time Frame: 1 year ]
  6. 2 year transplant-free survival [ Time Frame: 2 years ]
  7. 30 day new or worsened portal hypertensive decompensation [ Time Frame: 30 days ]
  8. 90 day new or worsened portal hypertensive decompensation [ Time Frame: 90 days ]
  9. 6 month new or worsened portal hypertensive decompensation [ Time Frame: 6 months ]
  10. 1 year new or worsened portal hypertensive decompensation [ Time Frame: 1 year ]
  11. 2 year new or worsened portal hypertensive decompensation [ Time Frame: 2 years ]
  12. 30 day unplanned hospitalization [ Time Frame: 30 days ]
  13. 90 day unplanned hospitalization [ Time Frame: 90 days ]
  14. 6 month unplanned hospitalization [ Time Frame: 6 month ]
  15. 1 year unplanned hospitalization [ Time Frame: 1 year ]
  16. 2 year unplanned hospitalization [ Time Frame: 2 year ]


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04642391


Contacts
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Contact: Brian J Wentworth, MD 4342432109 bw8xz@hscmail.mcc.virginia.edu

Locations
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United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22903
Contact: Brian J Wentworth, MD    434-243-2109    bw8xz@hscmail.mcc.virginia.edu   
Contact: Zachary H Henry, MD    434-243-2718    zhh6z@virginia.edu   
Sub-Investigator: Helmy Siragy, MD         
Sub-Investigator: Stephen Caldwell, MD         
Sub-Investigator: Curtis Argo, MD         
Sponsors and Collaborators
University of Virginia
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Responsible Party: Brian Wentworth, MD, Transplant Hepatology Fellow, University of Virginia
ClinicalTrials.gov Identifier: NCT04642391    
Other Study ID Numbers: 16007
First Posted: November 24, 2020    Key Record Dates
Last Update Posted: November 24, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Cirrhosis
Adrenal Insufficiency
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Cosyntropin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs