Clinical Study on Circadian Genes Dysregulation in Patients With Glucocorticoid Disorders

NCT04374721 | Unknown

• 1 other identifier: CHROnOS
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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)

Conditions

Cushing Syndrome; Adrenal Insufficiency; Cushing Disease; Addison Disease

Keywords

circadian rhythm; circadian genes; circadian clock; glucocorticoids; cortisol

Outcome Measures

Primary Outcomes (1)

• Circadian genes CLOCK and ARNTL expression evaluation

  Change in relative expression circadian genes of CLOCK and ARNLT from baseline compared to healthy controls. After PBMC isolation by Ficoll-Plaque gradient, complementary DNA (cDNA) pool will be extracted and used as the template for subsequent Polymerase Chain Reaction (PCR) amplification in Real time PCR; Gene expression will be quantified as relative expression compared to housekeeping genes.

  baseline, +1 month, +3 months, +6 months

Secondary Outcomes (13)

• Circadian gene expression profile

  baseline, +1 month, +3 months, +6 months

• Peripheral Blood Mononuclear Cells circadian profiling

  baseline, +1 month, +3 months, +6 months

• Circadian cortisol rhythm

  baseline, +1 month, +3 months, +6 months

• Sleep Disturbances

  baseline, +1 month, +3 months, +6 months

• Infectious Diseases Frequency and Severity

  baseline, +1 month, +3 months, +6 months

Study Arms (3)

Patients with Adrenal Insufficiency

EXPERIMENTAL

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

Diagnostic Test: circadian gene expression evaluation

Patients with Cushing's Syndrome

EXPERIMENTAL

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

Diagnostic Test: circadian gene expression evaluation

Healthy Controls

EXPERIMENTAL

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

Diagnostic Test: circadian gene expression evaluation

Interventions

circadian gene expression evaluation DIAGNOSTIC_TEST

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

Healthy Controls; Patients with Adrenal Insufficiency; Patients with Cushing's Syndrome

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \- 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

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Department of Experimental Medicine, "Sapienza" University of Rome

Roma, 00161, Italy

RECRUITING

MeSH Terms

Conditions

Cushing Syndrome; Adrenal Insufficiency; Pituitary ACTH Hypersecretion; Addison Disease

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Andrea Isidori, MD,PhD

CONTACT

0039649970711; andrea.isidori@uniroma1.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: patients will undergo circadian genes evaluation in peripheral blood mononuclear cells

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: May 5, 2020
• Study Start: July 4, 2018
• Primary Completion: June 1, 2023
• Study Completion: December 1, 2023
• Last Updated: November 30, 2022

Record last verified: 2022-11

Locations

IT (1)