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

Primary Purpose

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

Status
Unknown status
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
SGLT2 inhibitor
Sponsored by
University of Turin, Italy
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Diabetes Mellitus, Type 2 focused on measuring Sodium-Glucose Transporter 2 Inhibitors, Renin-Angiotensin System, Vasopressin, Natriuretic Peptide, Brain, Blood Pressure, Body Composition, Diabetes Mellitus, Type 2

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Mauro MaccarioRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diabetic patients

Arm Description

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

Outcomes

Primary Outcome Measures

Changes from baseline of antidiuretic function parameters (BNP)
Blood samples for BNP (pg/mL).
Changes from baseline of antidiuretic function parameters (BNP)
Blood samples for BNP (pg/mL).
Changes from baseline of antidiuretic function parameters (vasopressin)
Blood samples for Copeptin (pmol/L).
Changes from baseline of antidiuretic function parameters (vasopressin)
Blood samples for Copeptin (pmol/L).
Changes from baseline of antidiuretic function parameters (osmolality)
Samples for plasma osmolality (mOsm/Kg).
Changes from baseline of antidiuretic function parameters (osmolality)
Samples for urinary osmolality (mOsm/Kg).
Changes from baseline of antidiuretic function parameters (osmolality)
Samples for plasma osmolality (mOsm/Kg).
Changes from baseline of antidiuretic function parameters (osmolality)
Samples for urinary osmolality (mOsm/Kg).
Changes from baseline of antidiuretic function parameters (sodium balance)
Samples for serum sodium (mmol/L).
Changes from baseline of antidiuretic function parameters (sodium balance)
Samples for serum sodium (mmol/L).
Changes from baseline of antidiuretic function parameters (sodium balance)
Samples for urinary sodium (mmol/L).
Changes from baseline of antidiuretic function parameters (sodium balance)
Samples for urinary sodium (mmol/L).
Changes from baseline of antidiuretic function parameters (potassium balance)
Samples for serum potassium (mmol/L).
Changes from baseline of antidiuretic function parameters (potassium balance)
Samples for serum potassium (mmol/L).
Changes from baseline of antidiuretic function parameters (potassium balance)
Samples for urinary potassium (mmol/L).
Changes from baseline of antidiuretic function parameters (potassium balance)
Samples for urinary potassium (mmol/L).
Changes from baseline of renin-angiotensin-aldosterone system parameters (renin)
Blood samples for plasma renin activity (ng/mL/h).
Changes from baseline of renin-angiotensin-aldosterone system parameters (renin)
Blood samples for plasma renin activity (ng/mL/h).
Long term changes from baseline of renin-angiotensin-aldosterone system parameters aldosterone)
Blood samples for aldosterone (pg/mL).
Long term changes from baseline of renin-angiotensin-aldosterone system parameters
Blood samples for plasma renin activity (ng/mL/h) and aldosterone (pg/mL)

Secondary Outcome Measures

Changes from baseline of blood pressure values (ABPM)
Mean Systolic and Diastolic Blood Pressure (mmHg)
Changes from baseline of body composition
Variation of parameters of Bioelectrical Impedance Analysis (BIA)
Changes in basal glicemic control
Blood samples for basal glucose (mg/dL).
Changes in long term glicemic control
Blood samples for Glycated albumin (mmol/mol).

Full Information

First Posted
April 7, 2019
Last Updated
November 2, 2020
Sponsor
University of Turin, Italy
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1. Study Identification

Unique Protocol Identification Number
NCT03917758
Brief Title
Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Unknown status
Study Start Date
October 10, 2018 (Actual)
Primary Completion Date
July 30, 2020 (Actual)
Study Completion Date
October 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Turin, Italy

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Diabetic patients
Arm Type
Experimental
Arm Description
30 diabetic patients candidate to treatment with SGLT2i in add-on to metformin.
Intervention Type
Drug
Intervention Name(s)
SGLT2 inhibitor
Other Intervention Name(s)
Dapagliflozin, Empagliflozin, Canagliflozin
Intervention Description
Start of the treatment with SGLT2i.
Primary Outcome Measure Information:
Title
Changes from baseline of antidiuretic function parameters (BNP)
Description
Blood samples for BNP (pg/mL).
Time Frame
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (BNP)
Description
Blood samples for BNP (pg/mL).
Time Frame
90 days after starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (vasopressin)
Description
Blood samples for Copeptin (pmol/L).
Time Frame
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (vasopressin)
Description
Blood samples for Copeptin (pmol/L).
Time Frame
90 days after starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (osmolality)
Description
Samples for plasma osmolality (mOsm/Kg).
Time Frame
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (osmolality)
Description
Samples for urinary osmolality (mOsm/Kg).
Time Frame
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (osmolality)
Description
Samples for plasma osmolality (mOsm/Kg).
Time Frame
90 days after starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (osmolality)
Description
Samples for urinary osmolality (mOsm/Kg).
Time Frame
90 days after starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (sodium balance)
Description
Samples for serum sodium (mmol/L).
Time Frame
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (sodium balance)
Description
Samples for serum sodium (mmol/L).
Time Frame
90 days after starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (sodium balance)
Description
Samples for urinary sodium (mmol/L).
Time Frame
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (sodium balance)
Description
Samples for urinary sodium (mmol/L).
Time Frame
90 days after starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (potassium balance)
Description
Samples for serum potassium (mmol/L).
Time Frame
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (potassium balance)
Description
Samples for serum potassium (mmol/L).
Time Frame
90 days after starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (potassium balance)
Description
Samples for urinary potassium (mmol/L).
Time Frame
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Title
Changes from baseline of antidiuretic function parameters (potassium balance)
Description
Samples for urinary potassium (mmol/L).
Time Frame
90 days after starting SGLT2i therapy
Title
Changes from baseline of renin-angiotensin-aldosterone system parameters (renin)
Description
Blood samples for plasma renin activity (ng/mL/h).
Time Frame
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Title
Changes from baseline of renin-angiotensin-aldosterone system parameters (renin)
Description
Blood samples for plasma renin activity (ng/mL/h).
Time Frame
90 days after starting SGLT2i therapy
Title
Long term changes from baseline of renin-angiotensin-aldosterone system parameters aldosterone)
Description
Blood samples for aldosterone (pg/mL).
Time Frame
Before starting SGLT2i and 30 days the starting SGLT2i therapy
Title
Long term changes from baseline of renin-angiotensin-aldosterone system parameters
Description
Blood samples for plasma renin activity (ng/mL/h) and aldosterone (pg/mL)
Time Frame
90 days after starting SGLT2i therapy
Secondary Outcome Measure Information:
Title
Changes from baseline of blood pressure values (ABPM)
Description
Mean Systolic and Diastolic Blood Pressure (mmHg)
Time Frame
Before starting SGLT2i and 90 days after the starting
Title
Changes from baseline of body composition
Description
Variation of parameters of Bioelectrical Impedance Analysis (BIA)
Time Frame
Before starting SGLT2i and 90 days after the starting
Title
Changes in basal glicemic control
Description
Blood samples for basal glucose (mg/dL).
Time Frame
Before starting SGLT2i and 90 days after the starting
Title
Changes in long term glicemic control
Description
Blood samples for Glycated albumin (mmol/mol).
Time Frame
Before starting SGLT2i and 90 days after the starting

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mauro M Maccario, MD
Phone
00390116709559
Email
mauro.maccario@unito.it
First Name & Middle Initial & Last Name or Official Title & Degree
Mirko M Parasiliti Caprino, MD, PhD
Phone
00390116335544
Email
mirko.parasiliticaprino@unito.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mauro M Maccario, MD
Organizational Affiliation
Endocrinology, Diabetology and Metabolism; University of Turin
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ezio E Ghigo, MD
Organizational Affiliation
Endocrinology, Diabetology and Metabolism; University of Turin
Official's Role
Study Chair
Facility Information:
Facility Name
Mauro Maccario
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mauro M Maccario, MD
Phone
00390116709559
Email
mauro.maccario@unito.it
First Name & Middle Initial & Last Name & Degree
Mirko M Parasiliti Caprino, MD, PhD
Phone
00390116335544
Email
mirko.parasiliticaprino@unito.it
First Name & Middle Initial & Last Name & Degree
Nunzia N Prencipe, MD
First Name & Middle Initial & Last Name & Degree
Alessandro Maria A Berton, MD
First Name & Middle Initial & Last Name & Degree
Chiara C Lopez, MD
First Name & Middle Initial & Last Name & Degree
Chiara C Bona, MD
First Name & Middle Initial & Last Name & Degree
Andrea A Benso, MD, PhD
First Name & Middle Initial & Last Name & Degree
Silvia S Grottoli, MD
First Name & Middle Initial & Last Name & Degree
Ezio E Ghigo, MD
First Name & Middle Initial & Last Name & Degree
Mauro M Maccario, MD
First Name & Middle Initial & Last Name & Degree
Mirko M Parasiliti Caprino, MD, PhD
First Name & Middle Initial & Last Name & Degree
Fabio F Broglio, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27822054
Citation
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.
Results Reference
result
PubMed Identifier
26378978
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. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.
Results Reference
result
PubMed Identifier
23668478
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.
Results Reference
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PubMed Identifier
27802313
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(11):e0165703. doi: 10.1371/journal.pone.0165703. eCollection 2016.
Results Reference
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PubMed Identifier
24334175
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 Feb 4;129(5):587-97. doi: 10.1161/CIRCULATIONAHA.113.005081. Epub 2013 Dec 13.
Results Reference
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PubMed Identifier
23624546
Citation
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.
Results Reference
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PubMed Identifier
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Citation
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.
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Citation
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.
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Citation
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Antidiuretic Function Before and During Treatment With SGLT2 Inhibitors

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