[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"mild-autonomous-cortisol-secretion\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:mild-autonomous-cortisol-secretion":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,44,57],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":28,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":33,"startDateStruct":36,"completionDateStruct":38,"leadSponsor":40,"locationsCount":43},"100053534","phase-1-ketoconazole-effects-on-the-daily-cortisol-rhythm-in-mild-autonomous-cortisol-secretion-100053534",false,"NCT07649317","Ketoconazole Effects on the Daily Cortisol Rhythm in Mild Autonomous Cortisol Secretion","Ketoconazole Effects on Cortisol Circadian Rhythm in Mild Autonomous Cortisol Secretion: A Pilot Study","* INCLUSION CRITERIA:\n\nTo be eligible to participate in this study, an individual must meet all of the following criteria:\n\n1. Aged 18 years or older.\n2. Stated willingness to comply with all study procedures and availability for the duration of the study.\n3. Agreement to adhere to Lifestyle Considerations throughout the study.\n\nA. Subjects with Mild Autonomous Cortisol Secretion (MACS):\n\n1. Co-enrollment in protocol 19DK0066.\n2. Abnormal low-dose overnight dexamethasone suppression test (morning serum cortisol \\>1.8 mcg\u002FdL following 1 mg oral dexamethasone between 2300-0000h the evening prior)\n3. One or more \\>=1 cm adrenal nodule(s) on one or both adrenal glands on CT or MRI\n4. One normal 24-hour urine free cortisol value (per the reference range of the assay used).\n5. One morning plasma ACTH value \\\u003C10 pg\u002FmL.\n\nB. Healthy volunteers:\n\n1. In good general health as evidenced by medical history and physical examination; and in a stable state of health without ongoing acute\u002Ftemporary illness per the clinical judgment of the investigator.\n2. Normal low-dose overnight dexamethasone suppression test (morning serum cortisol \\\u003C=1.8 mcg\u002FdL following 1 mg oral dexamethasone between 2300-0000h the evening prior)\n3. Matching a participant with MACS who has completed testing in regard to:\n\n   * Age: Birth year within 5 years of that of the participant with MACS.\n   * Sex\n   * BMI (kg\u002Fm2) category: \\\u003C18.5 (underweight); 18.5-24.9 (normal weight); 25-29.9 (overweight); 30-34.9 (obesity class 1); 35-39.9 (obesity class 2); \\>=40 (obesity class 3).\n   * For women: menopausal status as judged by absence of menses for one year and FSH\\>15 mIU\u002FmL.\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n1. Inability to comply with all study procedures and visits.\n2. Inability of subject to understand or to sign a written informed consent document.\n3. Pregnancy or breastfeeding.\n4. Use of estrogen-containing oral contraceptives or oral estrogen therapy within 6 weeks before inpatient admission, due to possible increases in serum corticosteroid-binding globulin, and thereby total cortisol.\n5. Use of medications within 2 weeks before inpatient admission that can block glucocorticoid production or action: ketoconazole (systemic), levoketoconazole, metyrapone, osilodrostat, mifepristone.\n6. Use of oral, injectable, or inhaled glucocorticoids (unless intermittent, for symptomatic asthma) within the year before inpatient admission. Use of topical non-hydrocortisone containing potent glucocorticoids on more than 36 square inches within six months before inpatient admission.\n7. Anemia (hemoglobin \\\u003C13.7 g\u002FdL for males, \\\u003C11.2 g\u002FdL for females).\n8. Daily alcohol risk use (\\>2 standard drinks per day by self-report during screening visit).\n9. Severely uncontrolled diabetes mellitus (HbA1c \\>9.0%).\n10. Highly irregular sleep schedule in the week leading up to inpatient admission (e.g. shift work).\n11. Any contraindication to intravenous catheter use.\n12. Previous participation in this protocol.\n13. Any condition that in the opinion of the Investigator would jeopardize the participant s appropriate participation in this study.\n14. Any hematology or chemistry screening laboratory value drawn at screening that the Investigator deems clinically significant for exclusion.\n\nA. Subjects with Mild Autonomous Cortisol Secretion (MACS):\n\n1. Evidence of hyperaldosteronism, which must have been ruled out with serum aldosterone and plasma renin activity measurements if the participant has a history of hypertension or hypokalemia, per standard clinical care.\n2. Evidence of pheochromocytoma, which must have been ruled out with plasma or 24-hour urine metanephrines if an unenhanced adrenal nodule is \\>10 HU, per standard clinical care.\n3. Known allergy or hypersensitivity to ketoconazole.\n4. Significant liver disease or alanine aminotransferase (ALT) and\u002For aspartate aminotransferase (AST) \\>3xULN, and\u002For total bilirubin \\>1.5xULN during Screening.\n5. Prolonged QTc interval (\\>500 msec) on screening ECG.\n6. Use of medications in the 2 weeks before inpatient admission that can:\n\n   * Prolong QT when combined with ketoconazole (KTZ):\n\n     \\-- dofetilide, quinidine, pimozide, cisapride, methadone, disopyramide, dronedarone, ranolazine.\n   * Cause toxicity from increased concentration due to KTZ-induced CYP3A4 inhibition:\n\n     --methadone, disopyramide, dronedarone, ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine, methylergometrine, irinotecan, lurasidone, oral midazolam, alprazolam, triazolam, felodipine, nisoldipine, ranolazine, tolvaptan, eplerenone, lovastatin, simvastatin and colchicine.\n   * Inhibit CYP3A4 and increase KTZ bioavailability:\n\n     \\-- ritonavir, darunavir, fosamprenavir.\n   * Induce CYP3A4 and decrease KTZ bioavailability:\n\n     * Isoniazid, rifabutin, rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine.\n7. Inability to pause, for 24 hours, use of medication that reduces KTZ absorption: proton pump inhibitors (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole) and H2 antagonists (cimetidine, famotidine, nizatidine).\n\nInability to pause, for 3 hours, use of short-acting acid neutralizers that reduce KTZ absorption, e.g. aluminum hydroxide (acceptable if taken \\>=1 hour before or \\>=2 hours after KTZ).","ALL","18 Years","100 Years",{"count":20,"type":21},36,"ESTIMATED","INTERVENTIONAL",[24],"PHASE1","Background:\n\nCortisol is a hormone in the blood. Cortisol levels normally go down at night and up in the morning. Mild autonomous cortisol secretion (MACS) is a disease in which the body makes too much cortisol. MACS can cause high blood pressure, diabetes, and\u002For weight gain. Researchers think these problems may be caused by higher cortisol levels at night.\n\nObjective:\n\nTo compare daily cortisol levels in people with MACS with those in healthy people. Also, to test a drug (ketoconazole) that may help lower cortisol levels in people with MACS.\n\nEligibility:\n\nPeople aged 18 years and older with MACS. Healthy volunteers are also needed.\n\nDesign:\n\nParticipants with MACS will have a 2-night stay in the hospital.\n\nDay 1: A thin tube called a catheter will be inserted into a vein in the arm. Blood will be collected through the catheter every 2 hours starting at 8 PM. Participants will begin a 24-hour urine collection. Saliva will be collected every 6 hours for 24 hours.\n\nDay 2: Participants will take 2 tablets of the study drug ketoconazole with their evening meal. Blood will be collected via the catheter at regular intervals throughout the night.\n\nDay 3: Participants will leave the hospital in the morning.\n\nHealthy volunteers will be screened with a physical exam and blood tests. They will be tested to make sure they do not have MACS. To do this, they will take a drug (dexamethasone) at 11 PM on a day they choose; then they will return the next morning for a blood test.\n\nHealthy volunteers will have a 1-night stay in the hospital. They will have blood, urine, and saliva collected for 24 hours.",[27],"Mild Autonomous Cortisol Secretion",[29,30,27],"Cortisol","KETOCONAZOLE","RECRUITING","2026-07-10",{"date":34,"type":35},"2026-07-13","ACTUAL",{"date":37,"type":21},"2026-07-16",{"date":39,"type":21},"2027-12-31",{"name":41,"class":42},"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","NIH",1,{"id":45,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":46,"targetDuration":4,"studyType":22,"phases":47,"briefSummary":25,"conditions":48,"keywords":49,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":50,"lastUpdatePostDateStruct":51,"startDateStruct":53,"completionDateStruct":55,"leadSponsor":56,"locationsCount":43},"100641283",{"count":20,"type":21},[24],[27],[29,30,27],"2026-07-01",{"date":52,"type":35},"2026-07-02",{"date":54,"type":21},"2026-07-07",{"date":39,"type":21},{"name":41,"class":42},{"id":58,"slug":59,"hasResults":11,"nctId":60,"briefTitle":61,"officialTitle":61,"acronym":4,"eligibilityCriteria":62,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":63,"targetDuration":4,"studyType":22,"phases":65,"briefSummary":67,"conditions":68,"keywords":70,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":76,"lastUpdatePostDateStruct":77,"startDateStruct":79,"completionDateStruct":81,"leadSponsor":83,"locationsCount":43},"100601001","phase-2-impact-of-1-mg-osilodrostat-therapy-on-mild-autonomous-cortisol-secretion-macs-100601001","NCT07104812","Impact of 1 mg Osilodrostat Therapy on Mild Autonomous Cortisol Secretion (MACS)","Inclusion Criteria:\n\n* Provide written informed consent\n* Stated willingness to comply with all study procedures and availability for the duration of the study\n* Age ≥ 18 years\n* Diagnosed with MACS\n\n  * At least 2 abnormal post-dexamethasone cortisol results:\n\n    i. 1 mg post-dexamethasone cortisol \\>1.8 mcg\u002FdL or ii. 8 mg post-dexamethasone cortisol \\>1 mcg\u002FdL\n  * Historical dexamethasone suppression test results can be used if performed within 24 months prior to enrollment.\n* Adrenal imaging phenotype consistent with benign disease (adrenal adenoma\u002Fs, macronodular or micronodular adrenal hyperplasia)\n* At least one of the following comorbidities:\n\n  * Obesity (BMI\\>30 kg\u002Fm2)\n  * Dysglycemia\n  * Dyslipidemia\n  * Hypertension\n  * Osteopenia\n  * Osteoporosis\n  * Fragility fractures\n* Ability to take oral medication and be willing to adhere to the study intervention regimen\n* For persons of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤ 5% per year during the treatment period and for 1 month after the last dose of study treatment.\n\nExclusion Criteria:\n\n* Planned alternative therapy for MACS during the study period\n* Current use of oral exogenous glucocorticoid therapy\n* Current use of opioid therapy \\>20 MME\u002Fday\n* Planned use of oral exogenous glucocorticoid therapy\n* Planned use of opioid therapy \\>20 MME\u002Fday\n* Use of injectable glucocorticoid within the last 6 weeks or anticipated glucocorticoid use during the study period.\n* Hypokalemia of hypomagnesemia at baseline visit\n* Prolonged QTc on baseline ECG\n* Concomitant therapy with medications likely to lead to drug-drug interactions (based on PI review).\n* Investigator's judgement based on history\u002Fphysical examination that a comorbidity or concomitant medication may impact the hypothalamic-pituitary-adrenal axis or steroid metabolome\n* Uncontrolled intercurrent illness including, but not limited to:\n\n  * Ongoing or active infection\n  * Symptomatic congestive heart failure\n  * Unstable angina pectoris\n  * Cardiac arrhythmia\n  * Psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Pregnancy or lactation\n* Known allergic reactions to osilodrostat\n* Suspected false positive post-dexamethasone cortisol results due to increased metabolism, poor absorption, or noncompliance with dexamethasone.\n* Treatment with another investigational drug or other intervention within lower than specific therapy washout period",{"count":64,"type":21},15,[66],"PHASE2","The purpose of this study is to evaluate the safety and tolerability of 1 mg osilodrostat therapy in patients with mild autonomous cortisol secretion (MACS), and to determine the impact on 24h urine steroid metabolome and circadian cortisol\u002Fcortisone concentrations",[27,69],"Autonomous Cortisol Secretion (ACS)",[71,72,73,74,75],"hypercortisolism","cortisol excess","Adrenal adenoma","Adrenal hyperplasia","Cushing Syndrome","2026-02-08",{"date":78,"type":35},"2026-02-11",{"date":80,"type":35},"2026-01-14",{"date":82,"type":21},"2027-01",{"name":84,"class":85},"Mayo Clinic","OTHER"]