Clinical Study on Circadian Genes Dysregulation in Patients With Glucocorticoid Disorders

NCT ID: NCT04374721

Last Updated: 2022-11-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-04
• Study Completion Date: 2023-12-01

Brief Summary

This is a multicentric, prospective, intervention study on circadian genes expression in peripheral blood mononuclear cells as biomarkers of circadian rhythm derangement in patients affected by alterations of endogenous glucocorticoids secretion (Cushing's Syndrome during active phase, treatment and under remission and newly or on established glucocorticoid replacement therapy adrenal insufficiency)

Detailed Description

This is an intervention, prospective, multicentric study.

Enrolled patients will undergo 4 visits:

• Adrenal insufficiency (AI) patients: patients affected by primary or secondary adrenal insufficiency, whether newly diagnosed or on established glucocorticoid therapy, will be evaluated at baseline and after one, three and six months.
• Cushing's Syndrome (CS) patients: patients affected by Cushing's Syndrome will be evaluated at baseline during active phase of the disease and one, three and six months after treatment or remission. Patients affected by Cushing's Syndrome who will require glucocorticoid replacement therapy after remission will be evaluated three and six months after remission and then three and six months after the eventual glucocorticoid replacement therapy withdrawal. CS treatment will be surgery or medical therapy according to guidelines. Timing of medical therapy administration will change during protocol according to circadian rhythms.

Age-, sex- and BMI- matched healthy controls will be enrolled. Patients and controls will undergo the same procedures at baseline and after 1, 3 and 6 months.

The primary outcome measure will be the evaluation of circadian genes CLOCK and Aryl Hydrocarbon Receptor Nuclear Translocator Like (ARNTL) expression in peripheral blood mononuclear cells (PBMC) compared to healthy controls.

Secondary Outcomes measures will be:

• Circadian genes expression assessment compared to healthy controls at 7:00-8:00 Ante Meridiem (AM) (before breakfast), 12:00 AM (before lunch), 3:00-4:00 Post Meridiem (PM) (after lunch), 7:00 PM (before dinner), 12:00 PM;
• Immune profiling compared to healthy controls by the quantification of peripheral blood mononuclear cells (PBMC) subpopulations assessed by flow cytometry at 7:00-8:00 AM (before breakfast), 12:00 AM (before lunch), 3:00-4:00 PM (after lunch), 7:00 PM (before dinner), 12:00 PM;
• Evaluation of inflammatory cytokines and adipokines production compared to healthy controls at 7:00-8:00 AM (before breakfast), 12:00 AM (before lunch), 3:00-4:00 PM (after lunch), 7:00 PM (before dinner), 12:00 PM;
• Circadian cortisol rhythm by serum and salivary dosage at 7:00-8:00 AM (before breakfast), 12:00 AM (before lunch), 3:00-4:00 PM (after lunch), 7:00 PM (before dinner), 12:00 PM;
• Sleep disturbances evaluation by The Pittsburgh Sleep Quality Index (PSQI) self reported questionnaire
• Evaluation of infectious diseases frequencies and severity compared to healthy controls. Infectious diseases will be evaluated by an adaptation of Infectious Diseases Questionnaire (GNC)
• Circadian blood pressure using ambulatory blood pressure monitoring blood pressure waves for a noninvasive estimation
• Quality of life using SF-36-Item Health Survey questionnaire
• Psychometric Evaluation using Beck Depression Inventory questionnaire
• Evaluation of sexual dysfunction using FSFI questionnaire in woman and IIEF questionnaire in man
• Evaluation of insuline resistance calculated with HOMA index
• Evaluation of body weight (kg)
• Evaluation of blood lipid profile

Conditions

Cushing Syndrome; Adrenal Insufficiency; Cushing Disease; Addison Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Patients with Adrenal Insufficiency

Patients with Adrenal Insufficiency established or newly diagnosed, under glucocorticoid replacement therapy.

Group Type: EXPERIMENTAL

circadian gene expression evaluation

Intervention Type: DIAGNOSTIC_TEST

patients and controls will undergo circadian gene expression (CLOCK, ARNTL) evaluation at baseline and after 1, 3 and 6 months

Patients with Cushing's Syndrome

patients with adrenocorticotropic hormone (ACTH)-dependent or ACTH-independent Cushing's Syndrome diagnosis during active disease (new diagnosis or recidivating) at enrollment.

Group Type: EXPERIMENTAL

circadian gene expression evaluation

Intervention Type: DIAGNOSTIC_TEST

patients and controls will undergo circadian gene expression (CLOCK, ARNTL) evaluation at baseline and after 1, 3 and 6 months

Healthy Controls

Age-, sex- and BMI- matched patients referring to our center for diagnostic procedures not affected by Adrenal Insufficiency or Cushing's Syndrome.

Group Type: EXPERIMENTAL

circadian gene expression evaluation

Intervention Type: DIAGNOSTIC_TEST

patients and controls will undergo circadian gene expression (CLOCK, ARNTL) evaluation at baseline and after 1, 3 and 6 months

Interventions

circadian gene expression evaluation

patients and controls will undergo circadian gene expression (CLOCK, ARNTL) evaluation at baseline and after 1, 3 and 6 months

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Primary or secondary chronic adrenal insufficiency, previously or newly diagnosed.
• ACTH-dependent or ACTH-independent Cushing's Syndrome diagnosis during active disease (new diagnosis or recidivating).

• Signed informed consent to participate in the study.

Exclusion Criteria

• acute adrenal insufficiency;

• clinical or laboratory signs of significant respiratory, hepatobiliary, or pancreatic disease;
• pregnancy;
• severe infections, surgery, trauma requiring hospitalization within 3 months before study entry;
• any active blood or rheumatic disorders, and active liver disease in the previous 5 years;
• clinically significant chronic kidney disease;
• severe psychiatric diseases;
• history of neoplasms in the last 5 years (except for adrenal or pituitary adenoma in Cushing Syndrome, pituitary adenoma or related neolpasms in secondary adrenal insufficiency);
• heart disease with a class III or class IV functional capacity;
• BMI greater than 40 kg/m²;
• use of medication that interferes with cortisol metabolism within 1 month before study entry;
• treatment with systemic Glucocorticoid (GC) therapy other than hydrocortisone (HC), or cortisone acetate (CA);
• alcoholism and/or drug addictions;
• night-shift workers;
• use of melatonin, antipsychotic medications, estroprogestinic preparations

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Roma La Sapienza

OTHER

Sponsor Role: lead

Responsible Party

Andrea M. Isidori

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Experimental Medicine, "Sapienza" University of Rome

Roma, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Andrea Isidori, MD,PhD

Role: CONTACT

andrea.isidori@uniroma1.it

0039649970711

Facility Contacts

Andrea M Isidori, MD,PhD

Role: primary

andrea.isidori@uniroma1.it

0039649970711

Other Identifiers

CHROnOS

Identifier Type: -

Identifier Source: org_study_id