Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors

NCT03917758 | Unknown DMC

• 1 other identifier: GliRACo 1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (20)

• Changes from baseline of antidiuretic function parameters (BNP)

  Blood samples for BNP (pg/mL).

  Before starting SGLT2i and 30 days the starting SGLT2i therapy

• Changes from baseline of antidiuretic function parameters (BNP)

  Blood samples for BNP (pg/mL).

  90 days after starting SGLT2i therapy

• Changes from baseline of antidiuretic function parameters (vasopressin)

  Blood samples for Copeptin (pmol/L).

  Before starting SGLT2i and 30 days the starting SGLT2i therapy

• Changes from baseline of antidiuretic function parameters (vasopressin)

  Blood samples for Copeptin (pmol/L).

  90 days after starting SGLT2i therapy

• Changes from baseline of antidiuretic function parameters (osmolality)

  Samples for plasma osmolality (mOsm/Kg).

  Before starting SGLT2i and 30 days the starting SGLT2i therapy

• Changes from baseline of antidiuretic function parameters (osmolality)

  Samples for urinary osmolality (mOsm/Kg).

  Before starting SGLT2i and 30 days the starting SGLT2i therapy

• Changes from baseline of antidiuretic function parameters (osmolality)

  Samples for plasma osmolality (mOsm/Kg).

  90 days after starting SGLT2i therapy

• Changes from baseline of antidiuretic function parameters (osmolality)

  Samples for urinary osmolality (mOsm/Kg).

  90 days after starting SGLT2i therapy

• 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

• Changes from baseline of antidiuretic function parameters (sodium balance)

  Samples for serum sodium (mmol/L).

  90 days after starting SGLT2i therapy

• 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

• Changes from baseline of antidiuretic function parameters (sodium balance)

  Samples for urinary sodium (mmol/L).

  90 days after starting SGLT2i therapy

• 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

• Changes from baseline of antidiuretic function parameters (potassium balance)

  Samples for serum potassium (mmol/L).

  90 days after starting SGLT2i therapy

• 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

• Changes from baseline of antidiuretic function parameters (potassium balance)

  Samples for urinary potassium (mmol/L).

  90 days after starting SGLT2i therapy

• 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

• 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

• 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

• 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 Outcomes (4)

• Changes from baseline of blood pressure values (ABPM)

  Before starting SGLT2i and 90 days after the starting

• Changes from baseline of body composition

  Before starting SGLT2i and 90 days after the starting

• Changes in basal glicemic control

  Before starting SGLT2i and 90 days after the starting

• Changes in long term glicemic control

  Before starting SGLT2i and 90 days after the starting

Study Arms (1)

Diabetic patients

EXPERIMENTAL

30 diabetic patients candidate to treatment with SGLT2i in add-on to metformin.

Drug: SGLT2 inhibitor

Interventions

SGLT2 inhibitor DRUG

Start of the treatment with SGLT2i.

Also known as: Dapagliflozin, Empagliflozin, Canagliflozin

Diabetic patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diabetic patients;
• clinical indication to SGLT2i therapy.

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of Turin, Italy: lead

Study Sites (1)

Mauro Maccario

Turin, Piedmont, 10126, Italy

RECRUITING

Related Publications (10)

• Reed JW. Impact of sodium-glucose cotransporter 2 inhibitors on blood pressure. Vasc Health Risk Manag. 2016 Oct 27;12:393-405. doi: 10.2147/VHRM.S111991. eCollection 2016.

  PMID: 27822054 RESULT

• 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. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.

  PMID: 26378978 RESULT

• 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.

  PMID: 23668478 RESULT

• 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(11):e0165703. doi: 10.1371/journal.pone.0165703. eCollection 2016.

  PMID: 27802313 RESULT

• 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 Feb 4;129(5):587-97. doi: 10.1161/CIRCULATIONAHA.113.005081. Epub 2013 Dec 13.

  PMID: 24334175 RESULT

• 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 diabetes mellitus (ZODIAC-33). Diabetologia. 2013 Aug;56(8):1680-8. doi: 10.1007/s00125-013-2922-0. Epub 2013 Apr 28.

  PMID: 23624546 RESULT

• Nogueira-Silva L, Blanchard A, Curis E, Lorthioir A, Zhygalina V, Bergerot D, Baron S, Amar L, Bobrie G, Plouin PF, Menard J, Azizi M. Deciphering the Role of Vasopressin in Primary Aldosteronism. J Clin Endocrinol Metab. 2015 Sep;100(9):3297-303. doi: 10.1210/JC.2015-2007. Epub 2015 Jul 10.

  PMID: 26161452 RESULT

• Pikkemaat M, Melander O, Bengtsson Bostrom 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/j.jdiacomp.2015.07.006. Epub 2015 Jul 9.

  PMID: 26321369 RESULT

• 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 diabetes. Diabetes Care. 2013 Oct;36(10):3169-76. doi: 10.2337/dc13-0387. Epub 2013 Jun 4.

  PMID: 23735727 RESULT

• Berton AM, Parasiliti-Caprino M, Prencipe N, Bioletto F, Lopez C, Bona C, Caputo M, Rumbolo F, Ponzetto F, Settanni F, Gasco V, Mengozzi G, Ghigo E, Grottoli S, Maccario M, Benso AS. Copeptin adaptive response to SGLT2 inhibitors in patients with type 2 diabetes mellitus: The GliRACo study. Front Neurosci. 2023 Mar 20;17:1098404. doi: 10.3389/fnins.2023.1098404. eCollection 2023.

  PMID: 37021137 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertension; Body Weight Changes; Diabetes Insipidus

Interventions

Sodium-Glucose Transporter 2 Inhibitors; dapagliflozin; empagliflozin; Canagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Mauro M Maccario, MD

  Endocrinology, Diabetology and Metabolism; University of Turin

  PRINCIPAL INVESTIGATOR

• Ezio E Ghigo, MD

  Endocrinology, Diabetology and Metabolism; University of Turin

  STUDY CHAIR

Central Study Contacts

Mauro M Maccario, MD

CONTACT

00390116709559; mauro.maccario@unito.it

Mirko M Parasiliti Caprino, MD, PhD

CONTACT

00390116335544; mirko.parasiliticaprino@unito.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Professor

Study Record Dates

• First Submitted: April 7, 2019
• First Posted: April 17, 2019
• Study Start: October 10, 2018
• Primary Completion: July 30, 2020
• Study Completion: October 30, 2020
• Last Updated: November 3, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)