Clinical trial NCT03917758: Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors
Official title: Assessment of the Renin-angiotensin-aldosterone System (RAAS) and Antidiuretic Function in Patients With Type 2 Diabetes Before and During Treatment With Sodium-glucose Co-transporter 2 Inhibitors (SGLT2i): the GliRACo 1 Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Arterial Hypertension
Body Weight Changes
Keywords: Sodium-Glucose Transporter 2 Inhibitors
Renin-Angiotensin System
Vasopressin
Natriuretic Peptide, Brain
Blood Pressure
Body Composition
Diabetes Mellitus, Type 2
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2019-04-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Subjects treated with Canagliflozin, Dapagliflozin and Empagliflozin obtained improvement on blood pressure values, body weight and cardiovascular mortality but pathophysiological explanations of these effects are not yet known.

Detailed description: The pathophysiological explanations of the cardiovascular improvement of patients treated with SGLT2i are not yet known: osmotic diuresis and natriuresis, direct effects of weight reduction, increased in nitric oxide release, oxidative stress reduction, local renin-angiotensin-aldosterone system (RAAS) inhibition are the supposed mechanism. In the Literature the diuretic effect of SGLT2i therapy seems to be even stronger than thiazide or thiazide-like drugs. However, it is not defined the role of SGLT2i on antidiuretic function (RAAS, brain natriuretic peptide-BNP and antidiuretic hormone-ADH). Defining this relation could be important for:

* knowing effect of SGLT2i on RAAS (drugs interferences are important particularly during case detection of primary aldosteronism);
* discovering antidiuretic response to SGLT2i treatment and interactions between RAAS, BNP and ADH on the volume improvement induced by this new antidiabetic drugs.

In addition the aim of the study is to define effect of treatment on blood pressure and body composition.

Eligibility criteria: Inclusion Criteria:

* diabetic patients;
* clinical indication to SGLT2i therapy.

Exclusion Criteria:

* signs and symptoms of poor glycemic control (polydipsia, polyuria and weight loss);
* HbA1c \>10% or 86 mmol/mol;
* Body Mass Index (BMI) \> 40 Kg/m2;
* personal history of primary and secondary aldosteronism;
* personal history of heart failure;
* personal history of acute kidney injury;
* personal history of chronic kidney disease;
* personal history of liver cirrhosis;
* personal history of protein-wasting syndrome;
* personal history of renin secreting tumor;
* personal history of diabetes insipidus;
* personal history of syndrome of inappropriate antidiuresis (SIAD);
* personal history of hypocortisolism and hypercortisolism;
* therapy with Angiotensin Converting Enzyme inhibitors;
* therapy with Angiotensin Receptor Blockers;
* therapy with renin inhibitors;
* therapy with beta-blockers;
* therapy with alfa2-receptors agonists;
* therapy with Calcium Channel Blockers;
* therapy with diuretics;
* therapy with mineralocorticoid receptor antagonists;
* therapy with non steroidal and steroidal anti-inflammatory drugs.

Primary outcomes:
measure: Changes from baseline of antidiuretic function parameters (BNP)
timeFrame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (BNP)
timeFrame: 90 days after starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (vasopressin)
timeFrame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (vasopressin)
timeFrame: 90 days after starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (osmolality)
timeFrame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (osmolality)
timeFrame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (osmolality)
timeFrame: 90 days after starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (osmolality)
timeFrame: 90 days after starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (sodium balance)
timeFrame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (sodium balance)
timeFrame: 90 days after starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (sodium balance)
timeFrame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (sodium balance)
timeFrame: 90 days after starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (potassium balance)
timeFrame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (potassium balance)
timeFrame: 90 days after starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (potassium balance)
timeFrame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
measure: Changes from baseline of antidiuretic function parameters (potassium balance)
timeFrame: 90 days after starting SGLT2i therapy
measure: Changes from baseline of renin-angiotensin-aldosterone system parameters (renin)
timeFrame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
measure: Changes from baseline of renin-angiotensin-aldosterone system parameters (renin)
timeFrame: 90 days after starting SGLT2i therapy
measure: Long term changes from baseline of renin-angiotensin-aldosterone system parameters aldosterone)
timeFrame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
measure: Long term changes from baseline of renin-angiotensin-aldosterone system parameters
timeFrame: 90 days after starting SGLT2i therapy
Secondary outcomes:
measure: Changes from baseline of blood pressure values (ABPM)
timeFrame: Before starting SGLT2i and 90 days after the starting
measure: Changes from baseline of body composition
timeFrame: Before starting SGLT2i and 90 days after the starting
measure: Changes in basal glicemic control
timeFrame: Before starting SGLT2i and 90 days after the starting
measure: Changes in long term glicemic control
timeFrame: Before starting SGLT2i and 90 days after the starting
Other outcomes:
Locations:
city: Torino
country: Italy
facility: Mauro Maccario
state: Piemonte
Study officials:
affiliation: Endocrinology, Diabetology and Metabolism; University of Turin
name: Mauro M Maccario, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Endocrinology, Diabetology and Metabolism; University of Turin
name: Ezio E Ghigo, MD
role: STUDY_CHAIR
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