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

• ClinicalTrials.gov Identifier: NCT03343470
• Recruitment Status: Recruiting
• First Posted: November 17, 2017
• Last Update Posted: January 29, 2018
• Sponsor: University of Roma La Sapienza
• Collaborators: Federico II University; University of Palermo; University of Florence; Ospedali Riuniti Ancona; University of Padova
• Information provided by (Responsible Party): Andrea M. Isidori, University of Roma La Sapienza

Study Description

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.

Condition or disease
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 Design

• Study Type: Observational
• Estimated Enrollment: 15 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: The Observational Prospective Multicentric Study on Melatonin and Cortisol Circadian Rhythm in CusHing SyndrOme Patients in Active Phase and dUring RemiSsion.
• Actual Study Start Date: November 8, 2017
• Estimated Primary Completion Date: November 15, 2018
• Estimated Study Completion Date: December 30, 2018

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. 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
2. Evaluation of cortisol circadian rhythm [ Time Frame: 0, +3 months, +6 months ]
   single outcome measure of circadian cortisol secretion
3. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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

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

Contacts and Locations

Contacts

Contact: Andrea M Isidori, MD, PhD; +390649970540; andrea.isidori@uniroma1.it

Locations

Italy

Department of Experimental Medicine; Recruiting

Rome, Italy, 00161

Contact: Andrea M Isidori, MD, PhD +390649970540 andrea.isidori@uniroma1.it

Sponsors and Collaborators

University of Roma La Sapienza

Federico II University

University of Palermo

University of Florence

Ospedali Riuniti Ancona

University of Padova

Investigators

• Principal Investigator: Andrea M Isidori, MD, PhD; Dept. Experimental Medicine

More Information

Publications of 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. Review.

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.

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.

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.

• Responsible Party: Andrea M. Isidori, Assistant Professor, University of Roma La Sapienza
• ClinicalTrials.gov Identifier: NCT03343470 History of Changes
• Other Study ID Numbers: Adrenal_2
• First Posted: November 17, 2017
• Last Update Posted: January 29, 2018
• Last Verified: January 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Andrea M. Isidori, University of Roma La Sapienza:

Cushing Syndrome; Adrenal Insufficiency; Peripheral blood mononuclear cells; Melatonin; Cortisol; Immunological profile; Cushing Disease

Additional relevant MeSH terms:

Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cushing Syndrome; Syndrome; Disease; Pathologic Processes; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Melatonin; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Central Nervous System Depressants; Anti-Inflammatory Agents