Ignite Creation Date:
2025-12-25 @ 12:38 AM
Ignite Modification Date:
2025-12-25 @ 10:49 PM
Study NCT ID:
NCT00156767
Status:
COMPLETED
Last Update Posted:
2025-12-19
First Post:
2005-09-09
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Adrenal Function in Critical Illness
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000309', 'term': 'Adrenal Insufficiency'}], 'ancestors': [{'id': 'D000307', 'term': 'Adrenal Gland Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 225}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2004-11-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-03-28', 'lastUpdateSubmitDate': '2025-12-18', 'studyFirstSubmitDate': '2005-09-09', 'studyFirstSubmitQcDate': '2005-09-09', 'lastUpdatePostDateStruct': {'date': '2025-12-19', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2005-09-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Cortisol', 'timeFrame': 'after ACTH', 'description': 'cortisol increase'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['ACTH', 'Cortisol', 'Natural History'], 'conditions': ['Adrenal Insufficiency']}, 'referencesModule': {'references': [{'pmid': '25620457', 'type': 'DERIVED', 'citation': 'Abraham SB, Abel BS, Sinaii N, Saverino E, Wade M, Nieman LK. Primary vs secondary adrenal insufficiency: ACTH-stimulated aldosterone diagnostic cut-off values by tandem mass spectrometry. Clin Endocrinol (Oxf). 2015 Sep;83(3):308-14. doi: 10.1111/cen.12726. Epub 2015 Mar 20.'}], 'seeAlsoLinks': [{'url': 'https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2005-CH-0013.html', 'label': 'NIH Clinical Center Detailed Web Page'}]}, 'descriptionModule': {'briefSummary': '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.\n\n\\<TAB\\>\n\nPrevious 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.\n\n...', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '15 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': "NIH patients with Cushing's syndrome, adrenal insufficiency, hepatitis, nephrotic syndrome surrounding community healthy volunteers", 'healthyVolunteers': False, 'eligibilityCriteria': '* CRITERIA FOR ALL ARMS OF STUDY:\n\nWomen 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.\n\nCRITICAL CARE COMPONENT:\n\nINCLUSION CRITERIA:\n\nDiagnosis of sepsis by the primary clinical provider in the ICU.\n\nDiagnosis 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:\n\nInfection, documented or suspected, and some of the following:\n\nGeneral variables\n\n* Fever (core temperature greater than 38.3 C)\n* Hypothermia (core temperature greater than 36C)\n* Heart Rate greater than 90 min or greater than 2 SD above the normal value for age\n* Tachypnea\n* Altered mental status\n* Significant edema or positive fluid balance (greater than 20ml/kg over 24 hours)\n* Hyperglycemia (plasma glucose greater than 120 mg/dl) in the absence of diabetes\n\nInflammatory variables\n\n* Leukocytosis (WBC count greater than 12,000 uL)\n* Leukopenia (WBC count less than 4000 uL)\n* Normal WBC count with greater than 10 percent immature forms\n* Plasma C-reactive protein greater than 2 SD above the normal value\n* Plasma procalcitonin greater than 2 SD above the normal value\n\nHemodynamic variables\n\n* Arterial hypotension (SBP less than 90mm Hg, MAP less than 70, or an SBP decrease greater than 40 mm Hg in adults or less than 2 SD below normal for age)\n* SvO2 greater than 70 percent\n* Cardiac Index greater than 3.5L min(-1) M(-23)\n\nEXCLUSION CRITERIA:\n\nPregnancy\n\nAge less than 15 years at the Clinical Center; age less than 18 years at Georgetown or Suburban Hospitals\n\nOn 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.\n\nPatients 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)\n\nEnd 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)\n\nKnown 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.\n\nBONE MARROW TRANSPLANT COMPONENT:\n\nINCLUSION CRITERIA:\n\nParticipation 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.\n\nAgreement from the oncologist PI that the patient may participate in this protocol.\n\nEXCLUSION CRITERIA:\n\nThe presence of any contraindication to insulin tolerance testing-e.g.cardiovascular or cerebrovascular disease or any seizure history.\n\nPregnancy\n\nAge less than 15 years\n\nEnd stage renal or liver disease as defined under the critical care section\n\nKnown or anticipated blood withdrawal within 6 weeks that exceeds the NIH guidelines of 450 ml/six weeks in adults.\n\nHEALTHY VOLUNTEER COMPONENT:(Closed to recruitment)\n\nINCLUSION CRITERIA:\n\nAdults aged at least 18 years will be recruited.\n\nEXCLUSION CRITERIA:\n\nSevere hepatic, renal, cardiac, psychiatric or neurological illnesses\n\nMore 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.\n\nPregnancy\n\nKNOWN ADRENAL INSUFFICIENCY COMPONENT:\n\nINCLUSION CRITERIA:\n\nDocumented longstanding primary or secondary adrenal insufficiency\n\nEXCLUSION CRITERIA:\n\nPregnancy\n\nTRANSIENT ADRENAL INSUFFICIENCY COMPONENT:\n\nINCLUSION CRITERIA:\n\nRecent uncomplicated successful transsphemoidal surgery for Cushing s disease with serum cortisol level less than 5 micro g/dl\n\nTRANSIENT ADRENAL INSUFFICIENCY COMPONENT:\n\nEXCLUSION CRITERIA:\n\nSupra physiologic dosing of glucocorticoids as a treatment for another underlying medical disorder or surgical complication\n\nPregnancy\n\nCIRRHOSIS AND NEPHROTIC SYNDROME COMPONENT:\n\nAdults aged at least 18 years will be recruited.\n\nCIRRHOSIS\n\nINCLUSION CRITERIA:\n\n* Participation in an active NIDDK protocol entitled: Evaluation of patients with liver disease (91-DK-0214), with evidence of chronic liver disease\n* Agreement from the hepatologist PI that the patient may participate in this protocol.\n* Child-Pugh class A or B cirrhosis secondary to viral hepatitis\n* Absence of other significant medical illnesses that might interfere with prolonged follow-up evaluation\n* Normal renal function (creatinine clearance estimated as \\> 60 ml/min by the Modified Diet in Renal Disease (MDRD) equation and reported through our Clinical Research Information System (CRIS)).\n\nEXCLUSION CRITERIA:\n\n* History of the use of glucocorticoid therapy or medications that are known to interfere with HPA axis function within the past 6 months\n* Current symptoms of adrenal insufficiency (nausea, vomiting, weight loss, lightheadedness, unusual fatigue, salt craving, etc.).\n* Evidence of moderate-severe medical illness attributable to obstructive sleep apnea, heart or pulmonary failure, or active malignancy will be excluded.\n* Pregnancy\n* Known or anticipated blood withdrawal within 6 weeks that exceeds the NIH guidelines of 450 ml/six weeks in adults.\n\nNEPHROTIC SYNDROME:\n\nINCLUSION CRITERIA:\n\n* Participation in one of three active NIDDK protocols entitled: Rituximab plus cyclosporine in idiopathic membranous nephropathy (09-DK-0223), the Nephrotic Syndrome Study Network (Neptune) (11-DK-0023), or Pathogenesis of Glomerulosclerosis Study (94-DK-0127) with previously documented proteinuria \\>3.5g/day for 2 months or more or protein/creatinine ratio of 2.0 g/g on at least 2 occasions\n* Agreement from the nephrologist PI that the patient may participate in this protocol. Estimated GFR greater than or equal to 30 ml/min based on the MDRD equation and reported through CRIS.\n* Normal liver function as defined by normal liver function tests and no known history of liver disease.\n\nEXCLUSION CRITERIA:\n\n* History of the use of glucocorticoid therapy or medications that are known to interfere with HPA axis function within the past 6 months\n* Current symptoms of adrenal insufficiency (nausea, vomiting, weight loss, lightheadedness, unusual fatigue, salt craving, etc.).\n* Evidence of moderate-severe medical illness attributable to obstructive sleep apnea, heart or pulmonary failure, or active malignancy will be excluded.\n* Pregnancy\n* Known or anticipated blood withdrawal within 6 weeks that exceeds the NIH guidelines of 450 ml/six weeks in adults.'}, 'identificationModule': {'nctId': 'NCT00156767', 'briefTitle': 'Adrenal Function in Critical Illness', 'organization': {'class': 'NIH', 'fullName': 'National Institutes of Health Clinical Center (CC)'}, 'officialTitle': 'Adrenal Function in Critical Illness', 'orgStudyIdInfo': {'id': '050013'}, 'secondaryIdInfos': [{'id': '05-CH-0013'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'Bone Marrow Transplant', 'description': 'Patients enrolled in an NCI protocols for bone marrow transplant for breast cancer using prednisone treatment.'}, {'label': 'Cirrhosis', 'description': 'Adults on NIDDK protocol 91-DK-0213 with evidence of chronic liver disease with class A or B cirrhosis secondary to viral hepatitis'}, {'label': 'Critical Care', 'description': 'Patients with a diagnosis of sepsis by the primary clinical provider in the Emergency room of ICU'}, {'label': 'Healthy Volunteer', 'description': 'Healthy adult volunteers'}, {'label': 'Known Adrenal Insufficiency', 'description': 'patients with known diagnosis of Adrenal Insufficiency'}, {'label': 'Nephrotic Syndrome', 'description': 'Adults enrolled in NIDDK protocols with diagnosis of nephrotic syndrome'}, {'label': 'Post Surgical Treatment for Cushings', 'description': "Patients with transient adrenal insufficiency secondary to successful surgical treatment of cushing's syndrome"}]}, 'contactsLocationsModule': {'locations': [{'zip': '20892', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'National Institutes of Health Clinical Center', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}], 'overallOfficials': [{'name': 'Lynnette K Nieman, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}