Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors

NCT ID: NCT03917758

Last Updated: 2020-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-10

Study Completion Date

2020-10-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Diabetes Mellitus, Type 2 Arterial Hypertension Body Weight Changes

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Diabetic patients

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

Group Type EXPERIMENTAL

SGLT2 inhibitor

Intervention Type DRUG

Start of the treatment with SGLT2i.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

SGLT2 inhibitor

Start of the treatment with SGLT2i.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Dapagliflozin, Empagliflozin, Canagliflozin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Turin, Italy

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Mauro Maccario

Medical Doctor, Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Mauro M Maccario, MD

Role: PRINCIPAL_INVESTIGATOR

Endocrinology, Diabetology and Metabolism; University of Turin

Ezio E Ghigo, MD

Role: STUDY_CHAIR

Endocrinology, Diabetology and Metabolism; University of Turin

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Mauro Maccario

Turin, Piedmont, Italy

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Italy

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Mauro M Maccario, MD

Role: CONTACT

00390116709559

Mirko M Parasiliti Caprino, MD, PhD

Role: CONTACT

00390116335544

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Mauro M Maccario, MD

Role: primary

00390116709559

Mirko M Parasiliti Caprino, MD, PhD

Role: backup

00390116335544

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type RESULT
PMID: 27822054 (View on PubMed)

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.

Reference Type RESULT
PMID: 26378978 (View on PubMed)

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.

Reference Type RESULT
PMID: 23668478 (View on PubMed)

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.

Reference Type RESULT
PMID: 27802313 (View on PubMed)

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.

Reference Type RESULT
PMID: 24334175 (View on PubMed)

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.

Reference Type RESULT
PMID: 23624546 (View on PubMed)

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.

Reference Type RESULT
PMID: 26161452 (View on PubMed)

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.

Reference Type RESULT
PMID: 26321369 (View on PubMed)

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.

Reference Type RESULT
PMID: 23735727 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37021137 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

GliRACo 1

Identifier Type: -

Identifier Source: org_study_id