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Is Adrenal Insufficiency Under-diagnosed in Hospitalized Cirrhosis Patients?

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ClinicalTrials.gov Identifier: NCT03368066
Recruitment Status : Completed
First Posted : December 11, 2017
Last Update Posted : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
Zachary Henry, MD, University of Virginia

Tracking Information
First Submitted Date  ICMJE November 20, 2017
First Posted Date  ICMJE December 11, 2017
Last Update Posted Date September 13, 2019
Actual Study Start Date  ICMJE January 29, 2018
Actual Primary Completion Date March 12, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2017)
  • Cholesterol Esterification Deficiency [ Time Frame: 24 hours ]
    A percent quantification of serum cholesterol esterification will be measured via blood draw. Low values represent deficiency in esterification, which is a surrogate measure of lecthicin-cholesterol acetyltransferase (LCAT) enzymatic deficiency.
  • Spur Cell Anemia [ Time Frame: 24 hours ]
    A peripheral blood smear will be obtained and assessed for presence of acanthocytes (spur cells).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03368066 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2017)
  • Adrenal Insufficiency [ Time Frame: 24 hours ]
    A baseline total cortisol level will be obtained and then patients will receive a standard-dose synthetic ACTH (Cosyntropin) stimulation test to assess for the presence of adrenal insufficiency.
  • HDL Deficiency [ Time Frame: 24 hours ]
    Patients will have a lipid panel performed to assess for low HDL levels.
  • Free Cortisol Deficiency [ Time Frame: 24 hours ]
    Patients will have their free cortisol levels measured to assess for deficiency.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Is Adrenal Insufficiency Under-diagnosed in Hospitalized Cirrhosis Patients?
Official Title  ICMJE Is Adrenal Insufficiency Under-diagnosed in Hospitalized Cirrhosis Patients?
Brief Summary

The hepatoadrenal syndrome has been well described in the literature and is known to be associated with poorer outcomes in both stable and critically ill cirrhotic patients. In chronic liver disease, adrenal (and more specifically cortisol) insufficiency is thought to be a byproduct of altered lipid metabolism that results in decreased HDL production and thus decreased delivery of cholesterol to the adrenal for subsequent corticosteroid production. Studies to date have implicated lecithin-cholesterol acetyltransferase (LCAT) as the key enzyme which is deficient in some cirrhotic patients, leading to an impaired ability to esterify cholesterol and thus a loss of normal cellular functioning and membrane stability. The investigators seek to quantify this LCAT deficiency in a cohort of cirrhotic patients and demonstrate its association with various abnormal physiologies associated with chronic liver disease, including spur cell anemia, low HDL levels, and adrenal insufficiency.

Hospitalized cirrhotic patients at UVA that meet study eligibility criteria will be approached by a member of the study team to obtain consent for participation. If a patient agrees to become a study subject, they will have an approximate total of 35ml of blood drawn the following morning. Lab tests to be performed include: peripheral blood smear, lipid panel, free cortisol, cortisol binding globulin, serum cholesterol esters (surrogate for LCAT enzyme activity), and a standard-dose cortisol stimulation test. The latter involves blood drawn with the initial collection, administration of an intravenous 250mcg dose of synthetic ACTH, and then repeat small-volume blood draws at 30 minutes and 60 minutes later.

Subjects will be classified as adrenally sufficient or insufficient on the basis of as standard-dose cortisol stimulation test. Variables of interest for comparison between the groups include MELD score, Child-Turcotte-Pugh (CTP) classification, high-density lipoprotein (HDL) levels, presence of spur cell anemia, serum cholesterol ester percentage (surrogate for LCAT enzymatic activity), cortisol binding globulin levels, and free cortisol levels. Student's t-test and Chi Square tests will be utilized to determine significance; a p <0.05 value will be used as our threshold for significance. If multiple factors are found to be significantly different in a univariate fashion between classification groups, a multivariate logistic regression analysis will be performed for adjusted analysis. The investigators will also seek to define any correlations between variables. Furthermore, the investigators will assess correlation between MELD score and serum cholesterol ester percentage, spur cell anemia, HDL levels, cortisol binding globulin levels, and free cortisol levels; similar correlate analysis will be done using CTP classification instead of MELD score.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Adrenal Insufficiency
  • Cirrhosis
  • Spur Cell Anemia
  • Lecithin Acyltransferase Deficiency
Intervention  ICMJE Drug: Cosyntropin
Administer 250mcg cosyntropin to hospitalized cirrhosis patients to assess for the presence of adrenal insufficiency
Study Arms  ICMJE Experimental: Hospitalized cirrhosis patients
Administration of cortisol stimulation test to assess for presence or absence of adrenal insufficiency
Intervention: Drug: Cosyntropin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 12, 2019)
100
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2017)
120
Actual Study Completion Date  ICMJE March 12, 2019
Actual Primary Completion Date March 12, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age >=18 years
  • Diagnosis of cirrhosis
  • Admission to hospital

Exclusion Criteria:

  • Age < 18 years
  • Prior enrollment in study (i.e. readmission)
  • Prisoner
  • Pregnancy
  • Prednisone or Hydrocortisone use in last 24 hours
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 110 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03368066
Other Study ID Numbers  ICMJE 20212
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Zachary Henry, MD, University of Virginia
Study Sponsor  ICMJE University of Virginia
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Zachary Henry, MD University of Virginia School of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology
PRS Account University of Virginia
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP