Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors (GliRACo1)

November 2, 2020 updated by: Mauro Maccario, University of Turin, Italy

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Piemonte
      • Torino, Piemonte, Italy, 10126
        • Recruiting
        • Mauro Maccario
        • Contact:
        • Principal Investigator:
          • Mauro M Maccario, MD
        • Sub-Investigator:
          • Mirko M Parasiliti Caprino, MD, PhD
        • Sub-Investigator:
          • Chiara C Lopez, MD
        • Sub-Investigator:
          • Ezio E Ghigo, MD
        • Sub-Investigator:
          • Nunzia N Prencipe, MD
        • Sub-Investigator:
          • Andrea A Benso, MD, PhD
        • Contact:
        • Sub-Investigator:
          • Alessandro Maria A Berton, MD
        • Sub-Investigator:
          • Chiara C Bona, MD
        • Sub-Investigator:
          • Silvia S Grottoli, MD
        • Sub-Investigator:
          • Fabio F Broglio, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Diabetic patients
30 diabetic patients candidate to treatment with SGLT2i in add-on to metformin.
Drug: SGLT2 inhibitor
Start of the treatment with SGLT2i.
Other Names:
  • Dapagliflozin, Empagliflozin, Canagliflozin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes from baseline of antidiuretic function parameters (BNP)
Time Frame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
Blood samples for BNP (pg/mL).
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (BNP)
Time Frame: 90 days after starting SGLT2i therapy
Blood samples for BNP (pg/mL).
90 days after starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (vasopressin)
Time Frame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
Blood samples for Copeptin (pmol/L).
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (vasopressin)
Time Frame: 90 days after starting SGLT2i therapy
Blood samples for Copeptin (pmol/L).
90 days after starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (osmolality)
Time Frame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
Samples for plasma osmolality (mOsm/Kg).
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (osmolality)
Time Frame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
Samples for urinary osmolality (mOsm/Kg).
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (osmolality)
Time Frame: 90 days after starting SGLT2i therapy
Samples for plasma osmolality (mOsm/Kg).
90 days after starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (osmolality)
Time Frame: 90 days after starting SGLT2i therapy
Samples for urinary osmolality (mOsm/Kg).
90 days after starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (sodium balance)
Time Frame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
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)
Time Frame: 90 days after starting SGLT2i therapy
Samples for serum sodium (mmol/L).
90 days after starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (sodium balance)
Time Frame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
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)
Time Frame: 90 days after starting SGLT2i therapy
Samples for urinary sodium (mmol/L).
90 days after starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (potassium balance)
Time Frame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
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)
Time Frame: 90 days after starting SGLT2i therapy
Samples for serum potassium (mmol/L).
90 days after starting SGLT2i therapy
Changes from baseline of antidiuretic function parameters (potassium balance)
Time Frame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
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)
Time Frame: 90 days after starting SGLT2i therapy
Samples for urinary potassium (mmol/L).
90 days after starting SGLT2i therapy
Changes from baseline of renin-angiotensin-aldosterone system parameters (renin)
Time Frame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
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)
Time Frame: 90 days after starting SGLT2i therapy
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)
Time Frame: Before starting SGLT2i and 30 days the starting SGLT2i therapy
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
Time Frame: 90 days after starting SGLT2i therapy
Blood samples for plasma renin activity (ng/mL/h) and aldosterone (pg/mL)
90 days after starting SGLT2i therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes from baseline of blood pressure values (ABPM)
Time Frame: Before starting SGLT2i and 90 days after the starting
Mean Systolic and Diastolic Blood Pressure (mmHg)
Before starting SGLT2i and 90 days after the starting
Changes from baseline of body composition
Time Frame: Before starting SGLT2i and 90 days after the starting
Variation of parameters of Bioelectrical Impedance Analysis (BIA)
Before starting SGLT2i and 90 days after the starting
Changes in basal glicemic control
Time Frame: Before starting SGLT2i and 90 days after the starting
Blood samples for basal glucose (mg/dL).
Before starting SGLT2i and 90 days after the starting
Changes in long term glicemic control
Time Frame: Before starting SGLT2i and 90 days after the starting
Blood samples for Glycated albumin (mmol/mol).
Before starting SGLT2i and 90 days after the starting

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Turin, Italy

Investigators

  • Principal Investigator: Mauro M Maccario, MD, Endocrinology, Diabetology and Metabolism; University of Turin
  • Study Chair: Ezio E Ghigo, MD, Endocrinology, Diabetology and Metabolism; University of Turin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2018

Primary Completion (Actual)

July 30, 2020

Study Completion (Anticipated)

October 30, 2020

Study Registration Dates

First Submitted

April 7, 2019

First Submitted That Met QC Criteria

April 12, 2019

First Posted (Actual)

April 17, 2019

Study Record Updates

Last Update Posted (Actual)

November 3, 2020

Last Update Submitted That Met QC Criteria

November 2, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GliRACo 1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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