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

Completed

• Conditions: Cushing's Syndrome

• Registration Number: NCT02922257
• Lead Sponsor: Corcept Therapeutics

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2016-09-27
• Study First Submitted QC: 2016-09-30
• Study First Posted: 2016-10-04
• Study Start: 2016-11
• Primary Completion: 2018-10-30
• Study Completion: 2018-10-30
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-23
• Last Update Posted: 2019-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Gene expression levels	three years	Change in FKBP5 expression levels from baseline to after surgical treatment but prior to glucocorticoid replacement therapy