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Impact on Glycemic Variability After Treatment With Dapagliflozin on Type 2 Diabetes Patients

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ClinicalTrials.gov Identifier: NCT04090580
Recruitment Status : Recruiting
First Posted : September 16, 2019
Last Update Posted : September 26, 2019
Sponsor:
Collaborator:
AztraZeneca
Information provided by (Responsible Party):
Miguel Ángel Gómez Sámano, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Brief Summary:
Glycemic variability is refered as swings in glucemic concentration throughout the day, including preprandial and postprandial glucose, and it has been proposed that could be determinant in the development in microvascular complications of type 2 diabetes (Brownlee and Hirsch 2006) SGLT2 inhibitors (SGLT2i) are a novel group of medications for treating type 2 diabetes patients but their effect on glucose variability, and oxidative stress has not been determined as a primary endpoint in clinical trials of type 2 diabetes mellitus patients. The aim of this study is to compare the effect of SGLT2 inhibition on glucose variability, oxidative stress and inflammatory disease biomarkers (VCAM-1) on new onset type 2 DM patients.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Diagnostic Test: Continuous glucose monitoring Phase 4

Detailed Description:

The aim of this study is to compare the effect of SGLT2 inhibition on glucose variability, oxidative stress and inflammatory disease biomarkers (VCAM-1) on new onset type 2 DM patients. Methods: The investigators will include 36 patients with type 2 diabetes diagnosis with an Hba1c ≥ 7.5% and ≤ 9%, with BMI > 25 and <45 kg/m2, drug-naïve subjects. Subjects enrolled will be randomized 1:1 to either receive a daily dosage of dapagliflozin 10 mg and 2000 mg metformin for 12 weeks (n=18) or 2000 mg metformin (n=18). Patients who do not tolerate metformin at 2000mg dose will be downtitrated to 1500 mg daily. In case patients do not tolerate 1500 mg daily, they will be excluded. Patients who do not achieve glycaemic control, another antihyperglycaemic drug can be used.

Both groups will be monitored for 7 days using either iPro™ CGM system (Medtronic, Northridge, CA) or Dexcom G6 CGM (Dexcom Inc, San Diego, CA), or other available in Mexico. Basal continuous glucose monitoring will start at week 1 (first visit), and removed at day 7 and final continuous glucose monitoring will start at week 11 and removed 7 days after (final visit).

The main variables of interest are going to be in order of importance the delta of change (before and after study entry) of: 1.- glycaemic variability, 2.- change in Hba1c. 3.- change in oxidative stress status, 4. change in VCAM-1, 5.- change in weight, 6.- Blood pressure and 7.- waist circumference; before and after SGLT2i. The expected results are: compared to standard treatment, dapagliflozin arm will have lower glycaemic variability, higher reduction in Hba1c, lower oxidative stress, lower inflammsatory biomarker levels, and lower blood pressure


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact on Glycaemic Variability, Oxidative Stress and Inflammatory Disease Biomarkers After Treatment With Dapagliflozin as Dual Therapy With Metformin on Mexican Type 2 Diabetes Patients. A Randomized, Open-label Study
Actual Study Start Date : August 27, 2019
Estimated Primary Completion Date : January 27, 2020
Estimated Study Completion Date : August 27, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Daily dosage of dapagliflozin and metformin
Subjects enrolled will be randomized 1:1 to either receive a daily dosage of 10 mg dapagliflozin and 2000 mg metformin for 12 weeks
Diagnostic Test: Continuous glucose monitoring

Subjects enrolled will be randomized 1:1 to either receive a daily dosage of dapagliflozin 10 mg and 2000 mg metformin for 12 weeks (n=18) or 2000 mg metformin (n=18). Patients who do not tolerate metformin at 2000mg dose will be downtitrated to 1500 mg daily. In case patients do not tolerate 1500 mg daily, they will be excluded.

Both groups will be monitored for 7 days using either iPro™ CGM system (Medtronic, Northridge, CA) or Dexcom G6 CGM (Dexcom Inc, San Diego, CA). Basal continuous glucose monitoring will start at week 1 (first visit), and removed at day 7 and final continuous glucose monitoring will start at week 11 and removed 7 days after (final visit).


Experimental: Daily dosage of metformin
Subjects enrolled will be randomized 1:1 to either receive a daily dosage of 2000 mg metformin for 12 weeks
Diagnostic Test: Continuous glucose monitoring

Subjects enrolled will be randomized 1:1 to either receive a daily dosage of dapagliflozin 10 mg and 2000 mg metformin for 12 weeks (n=18) or 2000 mg metformin (n=18). Patients who do not tolerate metformin at 2000mg dose will be downtitrated to 1500 mg daily. In case patients do not tolerate 1500 mg daily, they will be excluded.

Both groups will be monitored for 7 days using either iPro™ CGM system (Medtronic, Northridge, CA) or Dexcom G6 CGM (Dexcom Inc, San Diego, CA). Basal continuous glucose monitoring will start at week 1 (first visit), and removed at day 7 and final continuous glucose monitoring will start at week 11 and removed 7 days after (final visit).





Primary Outcome Measures :
  1. Impact of dapagliflozin in glycemic variability [ Time Frame: 12 weeks ]
    Patients from both groups (dapagliflozin + metformin and metformin) will be monitored for 7 days using either iPro™ CGM system (Medtronic, Northridge, CA) or Dexcom G6 CGM (Dexcom Inc, San Diego, CA). Basal continuous glucose monitoring will start at week 1 (first visit), and removed at day 7 and final continuous glucose monitoring will start at week 11 and removed 7 days after (final visit) comparing glycemic variability between them. Mean difference of glycaemic variability (MAGE) calculated in mmol/L.


Secondary Outcome Measures :
  1. Impact of dapagliflozin in insulin level concentration [ Time Frame: 12 weeks ]
    Mean difference of insulin serum concentrations represented in μU/mL

  2. Impact of dapagliflozin in Hba1c [ Time Frame: 12 weeks ]
    Mean difference of HbA1c represented in %

  3. Impact of dapagliflozin on patients weight [ Time Frame: 12 weeks ]
    Mean difference of weight represented in kilograms

  4. Impact of dapagliflozin in blood pressure [ Time Frame: 12 weeks ]
    Mean difference of systolic and diastolic blood pressure represented in mmHg

  5. Impact of dapagliflozin in waist circumference [ Time Frame: 12 weeks ]
    Mean difference waist measured in centimeters



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Ages Eligible for Study:   18 Years to 77 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects > 18-77 years-old
  • Both Male and female
  • Hba1c ≥ 7.5 % and ≤9%
  • BMI > 25 and <45 kg/m2
  • Type 2 diabetes diagnosis, drug-naïve

Exclusion Criteria:

  • Hba1c > 9%
  • Creatinine clearance CKD-EPI: < 60 mL/min
  • LADA or Type 1 diabetes
  • Gestational diabetes
  • Clinically significant disease like: hepatic, hematological, oncological, psychiatric or rheumatic disease.
  • Symptoms of marked uncontrolled diabetes: (marked poliuria or polidipsia + 10% weight loss prior the last 3 months enrollement)
  • Known hypersensitivity to dapagliflozin or any of the excipients of the product
  • eGFR persistently <45 mL/min/1.73 m2
  • Unstable or rapidly progressing renal disease
  • Patients with severe hepatic impairment (Child-Pugh class C)
  • Any major CV event/Vascular Disease within 3 months prior to signing the consent at enrolment, as assessed by the investigator
  • For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.

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): NCT04090580


Contacts
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Contact: Miguel Angel Gomez Samano, MD 55 54870900 ext 2405 gsamano83@yahoo.com

Locations
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Mexico
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán ''INCMNSZ'' Recruiting
Ciudad de mexico, Mexico, 14080
Contact: Miguel Ángel Gómez Sámano, MD    55 54870900 ext 2405    miguelangelgomezsamano@gmail.com   
Principal Investigator: Miguel Angel Gómez Sámano, MD         
Sub-Investigator: Daniel Cuévas Ramos, MD         
Sub-Investigator: Francisco Javier Gómez Pérez, MD         
Sub-Investigator: Horacio Correa Carranza, MD         
Sub-Investigator: Alejandra Domínguez Sánchez, MD         
Sponsors and Collaborators
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
AztraZeneca
Investigators
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Principal Investigator: Miguel Angel Gomez Samano, MD Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
  Study Documents (Full-Text)

Documents provided by Miguel Ángel Gómez Sámano, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran:
Study Protocol  [PDF] June 11, 2018
Informed Consent Form  [PDF] August 22, 2019


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Responsible Party: Miguel Ángel Gómez Sámano, Principal Investigator, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
ClinicalTrials.gov Identifier: NCT04090580     History of Changes
Other Study ID Numbers: 3089
First Posted: September 16, 2019    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019

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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 Miguel Ángel Gómez Sámano, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran:
dapagliflozin
glycemic variability
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action