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Is Adrenal Insufficiency Under-diagnosed in Hospitalized Cirrhosis Patients?

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

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.


Condition or disease Intervention/treatment Phase
Adrenal Insufficiency Cirrhosis Spur Cell Anemia Lecithin Acyltransferase Deficiency Drug: Cosyntropin Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Is Adrenal Insufficiency Under-diagnosed in Hospitalized Cirrhosis Patients?
Estimated Study Start Date : December 15, 2017
Estimated Primary Completion Date : June 30, 2018
Estimated Study Completion Date : June 30, 2018


Arm Intervention/treatment
Experimental: Hospitalized cirrhosis patients
Administration of cortisol stimulation test to assess for presence or absence of adrenal insufficiency
Drug: Cosyntropin
Administer 250mcg cosyntropin to hospitalized cirrhosis patients to assess for the presence of adrenal insufficiency




Primary Outcome Measures :
  1. 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.

  2. Spur Cell Anemia [ Time Frame: 24 hours ]
    A peripheral blood smear will be obtained and assessed for presence of acanthocytes (spur cells).


Secondary Outcome Measures :
  1. 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.

  2. HDL Deficiency [ Time Frame: 24 hours ]
    Patients will have a lipid panel performed to assess for low HDL levels.

  3. Free Cortisol Deficiency [ Time Frame: 24 hours ]
    Patients will have their free cortisol levels measured to assess for deficiency.



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Ages Eligible for Study:   18 Years to 110 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT03368066


Contacts
Contact: Brian J Wentworth, MD 973-943-6781 bw8xz@hscmail.mcc.virginia.edu
Contact: Zachary Henry, MD 434-243-2718 zhh6z@hscmail.mcc.virginia.edu

Locations
United States, Virginia
University of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22903
Contact: Brian J Wentworth, MD    973-943-6781    bw8xz@hscmail.mcc.virginia.edu   
Contact: Zachary H Henry, MD    434-243-2718    zhh6z@virginia.edu   
Sponsors and Collaborators
University of Virginia
Investigators
Principal Investigator: Zachary Henry, MD University of Virginia School of Medicine, Department of Medicine, Division of Gastroenterology & Hepatology

Publications:

Responsible Party: Zachary Henry, MD, Principal Investigator, University of Virginia
ClinicalTrials.gov Identifier: NCT03368066     History of Changes
Other Study ID Numbers: 20212
First Posted: December 11, 2017    Key Record Dates
Last Update Posted: December 13, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Hypoalphalipoproteinemias
Fibrosis
Liver Cirrhosis
Adrenal Insufficiency
Lecithin Cholesterol Acyltransferase Deficiency
Pathologic Processes
Liver Diseases
Digestive System Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Hypolipoproteinemias
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Epinephrine
Racepinephrine
Epinephryl borate
Cosyntropin
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents