Cortisol Secretion, Sensitivity and Activity and Hypertension (PRECOR)

The goal of this observational study is to evaluate, between patients with arterial hypertension and non hypertensive control group,

• the prevalence of hidden hypercortisolism
• the relationship between organ damage and oxidative stress level, cortisol secretion degree, sensitivity and peripheral activity

Study Overview

• Status: Recruiting
• Conditions: Arterial Hypertension; Hypercortisolism
• Intervention / Treatment: Diagnostic test: Dexamethasone suppression test

• Study Type: Observational
• Enrollment (Anticipated): 290

Contacts and Locations

• Study Contact: Name: Carmen Aresta, MD; Phone Number: +3902619112506; Email: c.aresta@auxologico.it

Study Locations

• Italy
  • MI
    • Milan, MI, Italy, 20145
      • Recruiting
      • Istituto Auxologico Italiano IRCCS
      • Contact: Carmen Aresta, MD; Phone Number: +3902619112506; Email: c.aresta@auxologico.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Hypertension group: patients with hypertension referred to the cardiology clinics of Istituto Auxologico Italiano, Milan No hypertension group: patients without hypertension referred to endocrinology clinics of Istituto Auxologico Italiano for other diseases (e.g. euthyroid nodular goiter or chronic lymphocytic euthyroid thyroiditis)

Description

Inclusion Criteria:

• Hypertension group: arterial hypertension
• No hypertension group: absence of arterial hypertension

Exclusion Criteria:

• body mass index (BMI) >30 kg/m2
• active smoking (>20 cigarettes/day)
• pregnancy/lactation
• hypertension associated with family history of hypertension and cerebrovascular events before 40 years of age
• sleep apnea
• hypertension appearance in pre-pubertal age
• hypokalemia
• hypertension in the setting of an incidental adrenal mass
• classic signs and symptoms of hypercortisolism (lunar facies, striae, hypertrichosis, skin atrophy, hump)
• proven endocrine hypertension (pheochromocytoma, hyperaldosteronism, hyperparathyroidism, acromegaly, hyperthyroidism)
• renovascular hypertension
• diseases or conditions associated with increased activity of the hypothalamic-pituitary- adrenal axis and/or oxidative stress, such as type 2 diabetes, rheumatoid arthritis, severe rheumatic/autoimmune diseases, severe hematological diseases, alcoholism, depressive syndrome, chronic renal failure (GFR <45 ml/min), severe hypovitaminosis D (25OHvitaminD <10 ng/dL)
• therapies that interfere with the activity of the HPA axis (i.e. glucocorticoids, antidepressants).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
hypertension; Those patients suffering from arterial hypertension	Diagnostic test: Dexamethasone suppression test; Determination of cortisol levels at 9.00 am after taking 1 mg of dexamethasone the previous evening at 11.00 pm (1mg DST)
no hypertension; Those patients without arterial hypertension	Diagnostic test: Dexamethasone suppression test; Determination of cortisol levels at 9.00 am after taking 1 mg of dexamethasone the previous evening at 11.00 pm (1mg DST)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of hidden hypercortisolism (HidHyCo)	The presence of HidHyCo will be evaluated through the determination of cortisol levels at 9.00 am after taking 1 mg of dexamethasone the previous evening at 11.00 pm (1mgDST). In case of 1mgDST >1.8 µg/dL the patient will repeat the test and, if the result is confirmed, the patients is considered to have HidHyCo.	At baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of organ damage	Organ damage will be assessed by performing echocardiography, carotid echo-doppler (arterial stiffness) and microalbuminuria evaluation, which assess hypertensive heart disease, macro-angiopathy and hypertensive nephropathy, respectively	At baseline
Evaluation of oxidative stress level	The determination of the degree of oxidative stress will be carried out in all patients by evaluating the enzymatic activity of dipeptidyl peptidase 3 (DPP3) in the serum	At baseline
Evaluation of cortisol secretion degree	The cortisol secretion will be evaluated by measuring morning plasma ACTH and serum cortisol, 24-hour urinary free cortisol, serum cortisol at 09:00 after the administration of 1 mg dexamethasone at 11 PM on the previous day	At baseline
Evaluation of glucocorticoid sensitivity	In all subjects, genotyping of the N363S, BclI, ER22/23EK polymorphisms of the GR gene and of the polymorphisms will be performed	At baseline
Evaluation of glucocorticoid peripheral activity	Urinary free cortisol and urinary free cortisone will be measured in all subjects; their ratio will be used as measure of glucocorticoid peripheral activity	At baseline

Collaborators and Investigators

• Sponsor: Istituto Auxologico Italiano
• Investigators: Principal Investigator: Carmen Aresta, MD, Istituto Auxologico Italiano IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2021
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: March 10, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2023
• Last Update Submitted That Met QC Criteria: March 10, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: hypertension; hypercortisolism; hidden hypercortisolism; cortisol sensitivity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Endocrine System Diseases; Adrenal Gland Diseases; Hypersensitivity; Hypertension; Cushing Syndrome; Adrenocortical Hyperfunction; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: 05C921

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No