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Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors (GliRACo 1) (GliRACo1)

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ClinicalTrials.gov Identifier: NCT03917758
Recruitment Status : Recruiting
First Posted : April 17, 2019
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Mauro Maccario, University of Turin, Italy

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Arterial Hypertension Body Weight Changes Drug: SGLT2 inhibitor Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : October 10, 2018
Estimated Primary Completion Date : July 30, 2019
Estimated Study Completion Date : October 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Body Weight

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 Name: Dapagliflozin, Empagliflozin, Canagliflozin




Primary Outcome Measures :
  1. 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).

  2. Changes from baseline of antidiuretic function parameters (BNP) [ Time Frame: 90 days after starting SGLT2i therapy ]
    Blood samples for BNP (pg/mL).

  3. 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).

  4. Changes from baseline of antidiuretic function parameters (vasopressin) [ Time Frame: 90 days after starting SGLT2i therapy ]
    Blood samples for Copeptin (pmol/L).

  5. 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).

  6. 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).

  7. Changes from baseline of antidiuretic function parameters (osmolality) [ Time Frame: 90 days after starting SGLT2i therapy ]
    Samples for plasma osmolality (mOsm/Kg).

  8. Changes from baseline of antidiuretic function parameters (osmolality) [ Time Frame: 90 days after starting SGLT2i therapy ]
    Samples for urinary osmolality (mOsm/Kg).

  9. 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).

  10. Changes from baseline of antidiuretic function parameters (sodium balance) [ Time Frame: 90 days after starting SGLT2i therapy ]
    Samples for serum sodium (mmol/L).

  11. 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).

  12. Changes from baseline of antidiuretic function parameters (sodium balance) [ Time Frame: 90 days after starting SGLT2i therapy ]
    Samples for urinary sodium (mmol/L).

  13. 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).

  14. Changes from baseline of antidiuretic function parameters (potassium balance) [ Time Frame: 90 days after starting SGLT2i therapy ]
    Samples for serum potassium (mmol/L).

  15. 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).

  16. Changes from baseline of antidiuretic function parameters (potassium balance) [ Time Frame: 90 days after starting SGLT2i therapy ]
    Samples for urinary potassium (mmol/L).

  17. 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).

  18. 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).

  19. 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).

  20. 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)


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. Changes in basal glicemic control [ Time Frame: Before starting SGLT2i and 90 days after the starting ]
    Blood samples for basal glucose (mg/dL).

  4. Changes in long term glicemic control [ Time Frame: Before starting SGLT2i and 90 days after the starting ]
    Blood samples for Glycated albumin (mmol/mol).



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03917758


Contacts
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Contact: Mauro M Maccairo, MD 00390116709559 mauro.maccario@unito.it
Contact: Mirko M Parasiliti Caprino, MD, PhD 00390116335544 mirko.parasiliticaprino@unito.it

Locations
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Italy
Mauro Maccario Recruiting
Torino, Piemonte, Italy, 10126
Contact: Mauro M Maccario, MD    00390116709559    mauro.maccario@unito.it   
Contact: Mirko M Parasiliti Caprino, MD, PhD    00390116335544    mirko.parasiliticaprino@unito.it   
Sub-Investigator: Nunzia N Prencipe, MD         
Sub-Investigator: Alessandro Maria A Berton, MD         
Sub-Investigator: Chiara C Lopez, MD         
Sub-Investigator: Chiara C Bona, MD         
Sub-Investigator: Andrea A Benso, MD, PhD         
Sub-Investigator: Silvia S Grottoli, MD         
Sub-Investigator: Ezio E Ghigo, MD         
Principal Investigator: Mauro M Maccario, MD         
Sub-Investigator: Mirko M Parasiliti Caprino, MD, PhD         
Sponsors and Collaborators
University of Turin, Italy
Investigators
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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 of Results:

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Responsible Party: Mauro Maccario, Medical Doctor, Professor, University of Turin, Italy
ClinicalTrials.gov Identifier: NCT03917758     History of Changes
Other Study ID Numbers: GliRACo 1
First Posted: April 17, 2019    Key Record Dates
Last Update Posted: April 17, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Keywords provided by Mauro Maccario, University of Turin, Italy:
Sodium-Glucose Transporter 2 Inhibitors
Renin-Angiotensin System
Vasopressin
Natriuretic Peptide, Brain
Blood Pressure
Body Composition
Diabetes Mellitus, Type 2

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension
Body Weight
Body Weight Changes
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Diseases
Cardiovascular Diseases
Signs and Symptoms
Empagliflozin
Canagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs