Biomarker Expression in Patients With ACTH-Dependent Cushing's Syndrome Before and After Surgery

Study Overview
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Brief Summary
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This study will investigate the potential for FK506 binding protein 5 (FKBP5) (and other gene expression markers, for example pentraxin 3 [PTX-3], serum/glucocorticoid regulated kinase 1 [SGK1], and glycogen synthase kinase 3 beta [GSK3b]) to be developed as a biomarker for use in diagnosis of Cushing's syndrome, assessment of effectiveness of medical or surgical treatment, and detection of relapse of endogenous Cushing's syndrome after surgery.

Detailed Description
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This study will investigate the potential for FK506 binding protein 5 (FKBP5) (and other gene expression markers, for example pentraxin 3 [PTX-3], serum/glucocorticoid regulated kinase 1 [SGK1], and glycogen synthase kinase 3 beta [GSK3b]) to be developed as a biomarker for use in diagnosis of Cushing's syndrome, assessment of effectiveness of medical or surgical treatment, and detection of relapse of endogenous Cushing's syndrome after surgery. The primary study hypothesis is that FKBP5 levels are elevated in patients with Cushing's syndrome, and these levels decrease after successful surgical treatment. This is a non-randomized specimen collection study with pre- and post-surgery follow-up periods. This study will be performed in patients with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome scheduled for curative surgery and followed until relapse of endogenous Cushing's syndrome or up to 3 years post-surgery. No study medication will be given.

Official Title
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Prospective, Non-interventional Clinical Study of Biomarker Expression in Patients With ACTH-Dependent Cushing's Syndrome Before and After Surgery

Conditions
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Cushing's Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age. Has a documented diagnosis of ACTH-dependent, endogenous Cushing's syndrome and is scheduled for curative surgery. Must be able to comprehend and sign an approved Informed Consent Form (ICF) and other applicable study enrollment documents. Exclusion Criteria: Plans for pre-operative and/or intra-operative use of glucocorticoid (steroid cover). Use any of the following treatments for Cushing's syndrome, as specified: 4 weeks prior to first specimen collection and/or during the study period. Adrenostatic medications (metyrapone, ketoconazole, fluconazole, aminoglutethimide, LCI699 or etomidate etc). Short-acting somatostatin analogs (octreotide, pasireotide). 6 weeks prior to first specimen collection and/or during the study period. o Mifepristone. 8 weeks prior to first specimen collection and/or during the study period. o Neuromodulator drugs that act at the hypothalamic-pituitary level: serotonin antagonists (cyproheptadine, ketanserin, retanserin), dopamine agonists (bromocriptine, cabergoline), gamma-aminobutyric acid agonists (sodium valproate), and somatostatin receptor ligands (octreotide long-acting release [LAR], pasireotide LAR, lanreotide). Concomitant use of the following due to their potential to stimulate the expression of FKBP5: Testosterone or other steroid hormone analogues. Oral contraceptives or hormonal replacement therapy. History of illness that the Principal Investigator (PI) considers could interfere with or affect the conduct, results, and/or completion of the clinical trial. Pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene expression levels | Change in FKBP5 expression levels from baseline to after surgical treatment but prior to glucocorticoid replacement therapy | three years |