The Circadian Rhythm in CusHing SyndrOme in Active Phase and dUring RemiSsion (TheHOURS)

Overview

This is an observational, open, prospective multi-centre study designed to evaluate melatonin and cortisol circadian rhythm, immunological profile and anthropometric parameters in Cushing Syndrome patients during active Remission state.

Full Title of Study: “The Observational Prospective Multicentric Study on Melatonin and Cortisol Circadian Rhythm in CusHing SyndrOme Patients in Active Phase and dUring RemiSsion.”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: December 30, 2023

Detailed Description

Cushing Syndrome is a severe condition caused by prolonged exposure to high levels of glucocorticoids. This is a disease with high morbidity and mortality due to metabolic, cardiovascular, coagulative, psychiatric complications of hypercortisolism. The loss of circadian secretion of cortisol is one of the most sensitive and specific diagnostic features of Cushing's Syndrome that normalizes during remission. The evaluation of the circadian rhythm of cortisol is one of the diagnostic tests recommended by the guidelines to evaluate the state of the disease's activity. Studies in literature have shown several correlations between states of hypercortisolism and circadian secretion of melatonin, displaying reduced melatonin secretion throughout the day and the suppression of circadian rhythm of cortisol. However, the dynamics of the normalization of melatonin circadian rhythm during remission from Cushing syndrome are unclear. Therefore, the aim of our study is to evaluate the changes in circadian secretion of melatonin in Cushing's syndrome during active disease and during remission (3 and 6 months), according to the rational scientific influence of endogenous hypercortisolism on the function of the pineal gland. In addition, the changes in circadian secretion of cortisol, of mononuclear cells of the blood (PBMC) and of anthropometric-metabolic parameters, will be analyzed.

Arms, Groups and Cohorts

  • Cushing Syndrome (active phase)
    • Patients displaying biochemical and clinical features of active Cushing’s syndrome
  • Cushing Syndrome (during remission)
    • Patients at 3-6 months from remission with cortisol levels in the normal range

Clinical Trial Outcome Measures

Primary Measures

  • change from baseline in measurement of melatonin secretion at 3 and 6 months
    • Time Frame: 0, +3 months, +6 months
    • single outcome measurement of melatonin secretion

Secondary Measures

  • Evaluation of immunological profile at baseline, 3 and 6 months
    • Time Frame: 0, +3 months, +6 months
    • composite outcome measure consisting of simultaneous measurement of: PBMC profiling with flow cytometry, Full count blood cell
  • Evaluation of cortisol circadian rhythm
    • Time Frame: 0, +3 months, +6 months
    • single outcome measure of circadian cortisol secretion
  • Change from baseline in measurement of anthropometric-metabolic parameters at 3 and 6 months
    • Time Frame: 0, +3 months, +6 months
    • composite outcome measure consisting of simultaneous measurement of:body weight (kg), waist circumference (cm), blood pressure and pulse

Participating in This Clinical Trial

Inclusion Criteria

  • Cushing Syndrome during active phase Exclusion Criteria:

  • Malignancy – Alcoholism or drug addiction – Psychiatric disorders – Clinical or laboratory signs of significant cardiovascular, hepatobiliary disease – Clinically significant renal dysfunction – Pregnancy – Any medication with agents which could interfere with glucocorticoid kinetics and melatonin secretion

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Roma La Sapienza
  • Collaborator
    • Federico II University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Andrea M. Isidori, Assistant Professor – University of Roma La Sapienza
  • Overall Official(s)
    • Andrea M Isidori, MD, PhD, Principal Investigator, Dept. Experimental Medicine
  • Overall Contact(s)
    • Andrea M Isidori, MD, PhD, +390649970540, andrea.isidori@uniroma1.it

Citations Reporting on Results

Tomova A, Kumanov P, Robeva R, Manchev S, Konakchieva R. Melatonin secretion and non-specific immune responses are differentially expressed in corticotropin-dependent and corticotropin-independent Cushing's syndrome. Med Sci Monit. 2008 Jun;14(6):CR327-332.

Pivonello R, De Leo M, Cozzolino A, Colao A. The Treatment of Cushing's Disease. Endocr Rev. 2015 Aug;36(4):385-486. doi: 10.1210/er.2013-1048. Epub 2015 Jun 11.

Piovesan A, Terzolo M, Borretta G, Torta M, Buniva T, Osella G, Paccotti P, Angeli A. Circadian profile of serum melatonin in Cushing's disease and acromegaly. Chronobiol Int. 1990;7(3):259-61. doi: 10.3109/07420529009056984.

Fevre-Montange M, Tourniaire J, Estour B, Bajard L. 24 hour melatonin secretory pattern in Cushing's syndrome. Clin Endocrinol (Oxf). 1983 Aug;19(2):175-81. doi: 10.1111/j.1365-2265.1983.tb02979.x.

Angeli A, Gatti G, Sartori ML, Masera RG. Chronobiological aspects of the neuroendocrine-immune network. Regulation of human natural killer (NK) cell activity as a model. Chronobiologia. 1992 Jul-Dec;19(3-4):93-110. No abstract available.

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