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

The Observational Prospective Multicentric Study on Melatonin and Cortisol Circadian Rhythm in CusHing SyndrOme Patients in Active Phase and dUring RemiSsion.

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.

Study Overview

• Status: Recruiting
• Conditions: Cushing Syndrome

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.

• Study Type: Observational
• Enrollment (Anticipated): 15

Contacts and Locations

• Study Contact: Name: Andrea M Isidori, MD, PhD; Phone Number: +390649970540; Email: andrea.isidori@uniroma1.it

Study Locations

• Italy
  • Rome, Italy, 00161
    • Recruiting
    • Department of Experimental Medicine
    • Contact: Andrea M Isidori, MD, PhD; Phone Number: +390649970540; Email: andrea.isidori@uniroma1.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Cushing Syndrome patients in active phase and during remission at 3 and 6 months.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza
• Collaborators: University of Palermo; Federico II University; University of Padova; University of Florence; Ospedali Riuniti Ancona
• Investigators: Principal Investigator: Andrea M Isidori, MD, PhD, Dept. Experimental Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2017
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: November 10, 2017
• First Submitted That Met QC Criteria: November 10, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Melatonin; Cortisol; Cushing Disease; Peripheral blood mononuclear cells; Cushing Syndrome; Adrenal Insufficiency; Immunological profile
• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Syndrome; Cushing Syndrome
• Other Study ID Numbers: Adrenal_2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No