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

Cushing Syndrome Clinical Trial

— TheHOURS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03343470
• Other study ID #: Adrenal_2
• Status: Recruiting
• Start date: November 8, 2017
• Est. completion date: December 30, 2023

Study information

• Verified date: November 2022
• Source: University of Roma La Sapienza
• Contact: Andrea M Isidori, MD, PhD
• Phone: +390649970540
• Email: andrea.isidori[@]uniroma1.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cushing Syndrome
• Syndrome

Locations

Country	Name	City	State
Italy	Department of Experimental Medicine	Rome

Sponsors (6)

Lead Sponsor	Collaborator
University of Roma La Sapienza	Federico II University, Ospedali Riuniti Ancona, University of Florence, University of Padova, University of Palermo

Country where clinical trial is conducted

Italy, 

References & Publications (5)

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. Review. — View 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. — View 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. — View 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. Review. — View 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):CR327-33 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Evaluation of cortisol circadian rhythm	single outcome measure of circadian cortisol secretion	0, +3 months, +6 months
Secondary	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