Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors

Diabetes Mellitus, Type 2 Clinical Trial

— GliRACo1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03917758
• Other study ID #: GliRACo 1
• Status: Recruiting
• Phase: N/A
• Start date: October 10, 2018
• Est. completion date: October 30, 2020

Study information

• Verified date: November 2020
• Source: University of Turin, Italy
• Contact: Mauro M Maccario, MD
• Phone: 00390116709559
• Email: mauro.maccario[@]unito.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 30, 2020
• Est. primary completion date: July 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arterial Hypertension
• Body Weight
• Body Weight Changes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hypertension

Intervention

Drug:
• SGLT2 inhibitor
Start of the treatment with SGLT2i.

Locations

Country	Name	City	State
Italy	Mauro Maccario	Torino	Piemonte

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Boertien WE, Riphagen IJ, Drion I, Alkhalaf A, Bakker SJ, Groenier KH, Struck J, de Jong PE, Bilo HJ, Kleefstra N, Gansevoort RT. Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with di — View Citation

Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, Fagan NM, Woerle HJ, Johansen OE, Broedl UC, von Eynatten M. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014 — View Citation

DeFronzo RA, Hompesch M, Kasichayanula S, Liu X, Hong Y, Pfister M, Morrow LA, Leslie BR, Boulton DW, Ching A, LaCreta FP, Griffen SC. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 — View Citation

Lambers Heerspink HJ, de Zeeuw D, Wie L, Leslie B, List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013 Sep;15(9):853-62. doi: 10.1111/dom.12127. Epub 2013 Jun 5. — View Citation

Nogueira-Silva L, Blanchard A, Curis E, Lorthioir A, Zhygalina V, Bergerot D, Baron S, Amar L, Bobrie G, Plouin PF, Ménard J, Azizi M. Deciphering the Role of Vasopressin in Primary Aldosteronism. J Clin Endocrinol Metab. 2015 Sep;100(9):3297-303. doi: 10 — View Citation

Pikkemaat M, Melander O, Bengtsson Boström K. Association between copeptin and declining glomerular filtration rate in people with newly diagnosed diabetes. The Skaraborg Diabetes Register. J Diabetes Complications. 2015 Nov-Dec;29(8):1062-5. doi: 10.1016 — View Citation

Reed JW. Impact of sodium-glucose cotransporter 2 inhibitors on blood pressure. Vasc Health Risk Manag. 2016 Oct 27;12:393-405. eCollection 2016. Review. — View Citation

Shin SJ, Chung S, Kim SJ, Lee EM, Yoo YH, Kim JW, Ahn YB, Kim ES, Moon SD, Kim MJ, Ko SH. Effect of Sodium-Glucose Co-Transporter 2 Inhibitor, Dapagliflozin, on Renal Renin-Angiotensin System in an Animal Model of Type 2 Diabetes. PLoS One. 2016 Nov 1;11( — View Citation

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes from baseline of antidiuretic function parameters (BNP)	Blood samples for BNP (pg/mL).	Before starting SGLT2i and 30 days the starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (BNP)	Blood samples for BNP (pg/mL).	90 days after starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (vasopressin)	Blood samples for Copeptin (pmol/L).	Before starting SGLT2i and 30 days the starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (vasopressin)	Blood samples for Copeptin (pmol/L).	90 days after starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (osmolality)	Samples for plasma osmolality (mOsm/Kg).	Before starting SGLT2i and 30 days the starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (osmolality)	Samples for urinary osmolality (mOsm/Kg).	Before starting SGLT2i and 30 days the starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (osmolality)	Samples for plasma osmolality (mOsm/Kg).	90 days after starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (osmolality)	Samples for urinary osmolality (mOsm/Kg).	90 days after starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (sodium balance)	Samples for serum sodium (mmol/L).	Before starting SGLT2i and 30 days the starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (sodium balance)	Samples for serum sodium (mmol/L).	90 days after starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (sodium balance)	Samples for urinary sodium (mmol/L).	Before starting SGLT2i and 30 days the starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (sodium balance)	Samples for urinary sodium (mmol/L).	90 days after starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (potassium balance)	Samples for serum potassium (mmol/L).	Before starting SGLT2i and 30 days the starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (potassium balance)	Samples for serum potassium (mmol/L).	90 days after starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (potassium balance)	Samples for urinary potassium (mmol/L).	Before starting SGLT2i and 30 days the starting SGLT2i therapy
Primary	Changes from baseline of antidiuretic function parameters (potassium balance)	Samples for urinary potassium (mmol/L).	90 days after starting SGLT2i therapy
Primary	Changes from baseline of renin-angiotensin-aldosterone system parameters (renin)	Blood samples for plasma renin activity (ng/mL/h).	Before starting SGLT2i and 30 days the starting SGLT2i therapy
Primary	Changes from baseline of renin-angiotensin-aldosterone system parameters (renin)	Blood samples for plasma renin activity (ng/mL/h).	90 days after starting SGLT2i therapy
Primary	Long term changes from baseline of renin-angiotensin-aldosterone system parameters aldosterone)	Blood samples for aldosterone (pg/mL).	Before starting SGLT2i and 30 days the starting SGLT2i therapy
Primary	Long term changes from baseline of renin-angiotensin-aldosterone system parameters	Blood samples for plasma renin activity (ng/mL/h) and aldosterone (pg/mL)	90 days after starting SGLT2i therapy
Secondary	Changes from baseline of blood pressure values (ABPM)	Mean Systolic and Diastolic Blood Pressure (mmHg)	Before starting SGLT2i and 90 days after the starting
Secondary	Changes from baseline of body composition	Variation of parameters of Bioelectrical Impedance Analysis (BIA)	Before starting SGLT2i and 90 days after the starting
Secondary	Changes in basal glicemic control	Blood samples for basal glucose (mg/dL).	Before starting SGLT2i and 90 days after the starting
Secondary	Changes in long term glicemic control	Blood samples for Glycated albumin (mmol/mol).	Before starting SGLT2i and 90 days after the starting