Clinical trial NCT03343470: The Circadian Rhythm in CusHing SyndrOme in Active Phase and dUring RemiSsion (TheHOURS)
Official title: The Observational Prospective Multicentric Study on Melatonin and Cortisol Circadian Rhythm in CusHing SyndrOme Patients in Active Phase and dUring RemiSsion.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cushing Syndrome
Keywords: Cushing Syndrome
Adrenal Insufficiency
Peripheral blood mononuclear cells
Melatonin
Cortisol
Immunological profile
Cushing Disease
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
Collaborators: name: Federico II University
name: University of Palermo
name: University of Florence
name: Ospedali Riuniti Ancona
name: University of Padova
First posted: 2017-11-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cushing Syndrome patients in active phase and during remission at 3 and 6 months.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: change from baseline in measurement of melatonin secretion at 3 and 6 months
timeFrame: 0, +3 months, +6 months
Secondary outcomes:
measure: Evaluation of immunological profile at baseline, 3 and 6 months
timeFrame: 0, +3 months, +6 months
measure: Evaluation of cortisol circadian rhythm
timeFrame: 0, +3 months, +6 months
measure: Change from baseline in measurement of anthropometric-metabolic parameters at 3 and 6 months
timeFrame: 0, +3 months, +6 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Department of Experimental Medicine
Study officials:
affiliation: Dept. Experimental Medicine
name: Andrea M Isidori, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.