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Sponsored by: |
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00156767 |
An appropriate hypothalamic-pituitary-adrenal (HPA) axis response is required to survive critical illness. Primary adrenal insufficiency, relative adrenal insufficiency, tissue resistance to glucocorticoids, ACTH deficiency and immune-mediated inhibition of the HPA axis may impair the secretion or action of glucocorticoids in critically ill patients. Adrenal insufficiency is estimated to occur in up to 77% of critically ill patients, but currently, there is no consensus on the diagnostic criteria for adrenal insufficiency in this setting, and standard testing does not discriminate among the aforementioned factors. We will study the incidence and natural history of adrenal insufficiency in critically ill patients to further define adrenal insufficiency and provide data to develop diagnostic tests. Clinical features and outcomes will be correlated with laboratory measurements of hormones, cytokines and glucocorticoid action. Healthy volunteers will undergo cortrosyn tests with measurement of free cortisol levels to develop a normative range for this endpoint.
Previous glucocorticoid use, if prolonged and supraphysiologic, also inhibits the HPA and can result in adrenal insufficiency. Patients with short intermittent courses of glucocorticoid administration have not been studied well, and may also be at risk. To gain further information about this group, patients receiving pulse glucocorticoid doses as part of bone marrow transplant regimens at the Clinical Center will also be studied.
Condition |
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Adrenal Insufficiency |
Study Type: | Observational |
Official Title: | Adrenal Function in Critical Illness |
Study Start Date: | October 2004 |
An appropriate hypothalamic-pituitary-adrenal (HPA) axis response is required to survive critical illness. Primary adrenal insufficiency, relative adrenal insufficiency, tissue resistance to glucocorticoids, ACTH deficiency and immune-mediated inhibition of the HPA axis may impair the secretion or action of glucocorticoids in critically ill patients. Adrenal insufficiency is estimated to occur in up to 77 percent of critically ill patients, but currently, there is no consensus on the diagnostic criteria for adrenal insufficiency in this setting, and standard testing does not discriminate among the aforementioned factors. We will study the incidence and natural history of adrenal insufficiency in critically ill patients to further define adrenal insufficiency and provide data to develop diagnostic tests. Clinical features and outcomes will be correlated with laboratory measurements of hormones, cytokines and glucocorticoid action. Healthy volunteers will undergo cortrosyn tests with measurement of free cortisol levels to develop a normative range for this endpoint. Patients with known adrenal insufficiency will also be studied to help determine the clinical utility of diagnostic tests among these different groups.
Previous glucocorticoid use, if prolonged and supraphysiologic, also inhibits the HPA axis and can result in adrenal insufficiency. Patients with short intermittent courses of glucocorticoid administration have not been studied well, and may also be at risk. To gain further information about this group, patients receiving pulse glucocorticoid doses as part of bone marrow transplant regimens at the Clinical Center will also be studied.
Ages Eligible for Study: | 15 Years to 85 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Women of reproductive age will also undergo a pregnancy test (urine hCG) prior to starting the testing procedure. If the woman is determined to be pregnant, she will not be able to participate in this study.
INCLUSION CRITERIA - CRITICAL CARE COMPONENT:
Diagnosis of sepsis by the primary clinical provider in the ICU.
Diagnosis of the above is based on diagnostic criteria for sepsis as defined by the 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference as listed below:
Infection, documented or suspected, and some of the following:
General variables
Inflammatory variables
Hemodynamic variables
EXCLUSION CRITERIA - CRITICAL CARE COMPONENT:
Pregnancy
Age less than 15 years at the Clinical Center; age less than 18 years at Georgetown or Suburban Hospitals
On glucocorticoids or megace within two weeks of admission unless using more than one of the following medications, patients taking inhaled corticosteriods (less than 1.5 mg/day budesonide, beclomethasone dipropionate and triamcinolone acetonide and less thab 0.75 mg/day for fluticasone propionate) or intranasal corticosteriods will not be excluded.
Patients who have received chronic steroid suppressive medications, i.e. etomidate, ketoconazole (Patients receiving etomidate for intubation purposes as a one time dose will not be excluded)
End stage renal or liver disease (creatinine clearance estimated as less than 20 cc/min by the cockcroft-gault equation: (140 - age) times lean body weight (kg)/ pCr (mg/dl) times 72, in patients with stable renal function; patients requiring dialysis; acute or fulminant hepatitis, alcoholic hepatitis, chronic severe hepatitis, severe obstructive hepatitis, severe coagulopathy, extrahepatic manifestations of ESLD, i.e. hypoxia, cardiomyopathy, acute renal failure)
Known or anticipated blood withdrawal within 6 weeks that exceeds the NIH guidelines of 450 l/six weeks in adults or 7 ml/kg/six weeks in children.
INCLUSION CRITERIA - BONE MARROW TRANSPLANT COMPONENT:
Participation in a Clinical Center bone marrow transplant protocol for breast cancer (generally Allogeneic Breast Protocol 2: Phase 1 Trial of T cell Exchange with Th2/Tc2 Cells for Allogeneic Stem Cell Transplantation after Reduced Intensity Conditioning for Metastatic Breast Cancer), or for hematologic malignancy (generally either: T-cell depleted, reduced intensity allogeneic stem cell transplant from haploidentical related donors for hematologic malignancies: A sequential dose escalation study of donor Th2/Tc2 cells or Th2, Sirolimus in Allogeneic HSCT.
Agreement from the oncologist PI that the patient may participate in this protocol.
EXCLUSION CRITERIA - BONE MARROW TRANSPLANT COMPONENT:
The presence of any contraindication to insulin tolerance testing-e.g.cardiovascular or cerebrovascular disease or any seizure history.
Pregnancy
Age less than 15 years
End stage renal or liver disease as defined under the critical care section
Known or anticipated blood withdrawal within 6 weeks that exceeds the NIH guidelines of 450 ml/six weeks in adults.
INCLUSION CRITERIA - HEALTHY VOLUNTEER COMPONENT:
Adults aged at least 18 years will be recruited.
EXCLUSION CRITERIA - HEALTHY VOLUNTEER COMPONENT:
Severe hepatic, renal, cardiac, psychiatric or neurological illnesses
More than two weeks of oral antifungal or glucocorticoid medications or near daily use of topical glucocorticoids with broken skin. Frequent use of topical antifungal agents will be considered on a case-by-case basis.
Pregnancy
INCLUSION CRITERIA - KNOWN ADRENAL INSUFICIENTY COMPONENT:
Documented longstanding primary or secondary adrenal insufficiency
EXCLUSION CRITERIA - KNOWN ADRENAL INSUFFICNCY COMPONENT:
Pregnancy
INCLUSION CRITERIA - TRANSIENT ADRENAL INSUFICIENTY COMPONENT:
Recent uncomplicated successful transsphemoidal surgery for Cushing's disease with serum cortisol level less than 5 micro g/dl
EXCLUSION CRITERIA - TRANSIENT ADRENAL INSUFFICNCY COMPONENT:
Supra physiologic dosing of glucocorticoids as a treatment for another underlying medical disorder or surgical complication
Pregnancy
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 | |
Suburban Hospital | Recruiting |
Bethesda, Maryland, United States, 20814 |
Study ID Numbers: | 050013, 05-CH-0013 |
Study First Received: | September 9, 2005 |
Last Updated: | December 10, 2008 |
ClinicalTrials.gov Identifier: | NCT00156767 |
Health Authority: | United States: Federal Government |
Critical Care Adrenal Insufficiency Septic Shock Cortrosyn Steroids Cortisol |
Critical Care Unit Adrenal Insufficiency Adrenal Gland Function Healthy Volunteer HV |
Adrenal Insufficiency Addison's disease Hydrocortisone Autoimmune Diseases Cortisol succinate Adrenal Gland Diseases Endocrine System Diseases Cosyntropin Healthy Hypoadrenalism |
Adrenal gland hypofunction Shock Critical Illness Adrenoleukodystrophy Shock, Septic Addison Disease Hydrocortisone acetate Endocrinopathy Epinephrine X-linked adrenoleukodystrophy |
Disease Attributes Pathologic Processes Immune System Diseases |