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SGLT-2 Inhibition, Metabolomics and Cardiovascular/Kidney Disease

Primary Purpose

Type 2 Diabetes Mellitus

Status
Unknown status
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Dapagliflozin 10 mg
Placebo Oral Tablet
Sponsored by
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 2 Diabetes Mellitus focused on measuring Metabolomics, Dapagliflozin

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 18-75.
  • BMI 27-39.9 kg/m2.
  • T2DM on treatment with metformin and inadequate metabolic control (defined as HbA1c≥6.5 -7%).

Exclusion Criteria:

  • Pregnancy (all women of child-bearing age, unless on treatment with contraceptive methods, will undergo a pregnancy test)
  • Breastfeeding
  • Intolerance/allergy to dapagliflozin.
  • Treatment with antidiabetic drug other than metformin.
  • Impaired kidney function: Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 (calculated using the CKD-EPI formula).
  • Patients with established cardiovascular disease.
  • Previous or current history of cancer of any kind.
  • Uncontrolled hypertension (systolic blood pressure≥160 mmHg or diastolic blood pressure≥110 mmHg, despite adequate antihypertensive treatment).
  • History of liver tumour or acute or chronic liver disease with impaired liver function: total bilirubin levels> 2.0 mg / dl or GOT/GPT levels three times higher than normal upper limit.
  • Known HIV infection or active HBV or HCV infection.
  • Other serious underlying diseases, which could affect the patient's ability to participate in the study.
  • Reduced life expectancy (<12 months) due to advanced or terminal concomitant diseases.

In addition, female patients of child-bearing age will be advised to use contraceptive methods during the study period, given the contraindication of dapagliflozin and metformin during pregnancy as per normal clinical practice.

Sites / Locations

  • Virgen de la Victoria University Hospital. Endocrinology Department

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dapagliflozin

Placebo

Arm Description

Dapagliflozin 10 mg daily (orally)

Matching placebo for dapagliflozin daily (orally). Does not contain active ingredient

Outcomes

Primary Outcome Measures

Metabolomics changes in blood
Targeted and quantitative analysis by ultra-high-resolution liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ/MS). Analysis of specific families of metabolites selected from hypotheses generated by previous exploratory studies: changes in acylcarnitines and other intermediates of mitochondrial β-oxidation and the urea cycle, branched-chain amino acids and biogenic amines
Metabolomics changes in urine
Targeted and quantitative analysis by ultra-high-resolution liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ/MS). Analysis of specific families of metabolites selected from hypotheses generated by previous exploratory studies: changes in acylcarnitines and other intermediates of mitochondrial β-oxidation and the urea cycle, branched-chain amino acids and biogenic amines

Secondary Outcome Measures

BMI (body mass index) changes
Measured by body composition analysis
Changes in insulin resistance
Measured as HOMA-IR (homeostatic model assessment of insulin resistance)
Changes in metabolic control
Measured as HbA1c (glycated hemoglobin)
Changes in Quality of Life: 36-Item Short Form Health Survey (SF-36) questionnaire
The SF-36 has eight scaled scores: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The scores are weighted sums of the questions in each section. Scores range from 0 - 100, lower scores indicate more disability, and higher scores indicate less disability
Changes in albuminuria
Modifications in albuminuria, measured as albumin excretion rate (AER)

Full Information

First Posted
April 11, 2019
Last Updated
April 22, 2019
Sponsor
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
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1. Study Identification

Unique Protocol Identification Number
NCT03919656
Brief Title
SGLT-2 Inhibition, Metabolomics and Cardiovascular/Kidney Disease
Official Title
SGLT-2 Inhibition and Cardiovascular Disease. Metabolomics Study of Potential Factors Involved in Cardio- and Nephroprotection
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
May 2019 (Anticipated)
Primary Completion Date
December 2019 (Anticipated)
Study Completion Date
April 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

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
This study evaluates the metabolomics changes associated with dapagliflozin treatment in patients with type 2 diabetes mellitus (T2DM). The participants in the study will be randomized to receive 10 mg dapagliflozin or placebo once daily for 12 weeks.
Detailed Description
In this study, we hypothesize that metabolomics changes that occur in patients with T2DM after initiating SGLT2i (sodium-glucose cotransporter 2 inhibitors) treatment may be responsible for the beneficial cardiovascular and kidney effects observed in clinical trials with SGLT2i. Also, we propose that the study of the specific metabolome associated with the treatment with SGLT2i could help identify the possible metabolites and molecules that reduce CVD (cardiovascular disease) and renal disease in patients with T2DM. The participants in the study will be randomized to receive 10 mg dapagliflozin or placebo once daily of for 12 weeks. Besides, all participants will be advised to engage in 150 min or more of moderate-to vigorous intensity physical activity per week, spread over at least 3 days/week, with no more than 2 consecutive days without activity and to engage in 2-3 sessions/week of resistance exercise on nonconsecutive days. Moreover, these patients will be advised to follow a lifestyle program that achieve a 500-750 kcal/day energy deficit or provide≈1,200-1,500 kcal/day for women and 1,500-1,800 kcal/day for men, adjusted for the individual's baseline body weight.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
Metabolomics, Dapagliflozin

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Patients will be randomized in a 1:1 ratio
Masking
ParticipantInvestigator
Masking Description
Dapagliflozin 10 mg, Green, plain, diamond shaped, film coated tablet (orally); Matching placebo for dapagliflozin Green, plain, diamond shaped, film coated tablet (orally). Does not contain active ingredient
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dapagliflozin
Arm Type
Experimental
Arm Description
Dapagliflozin 10 mg daily (orally)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo for dapagliflozin daily (orally). Does not contain active ingredient
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 10 mg
Other Intervention Name(s)
Farxiga 10 mg
Intervention Description
Dapagliflozin 10 mg daily in a green, plain, diamond shaped, film coated tablet (orally)
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Green, plain, diamond shaped, film coated tablet (orally). Does not contain active ingredient
Primary Outcome Measure Information:
Title
Metabolomics changes in blood
Description
Targeted and quantitative analysis by ultra-high-resolution liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ/MS). Analysis of specific families of metabolites selected from hypotheses generated by previous exploratory studies: changes in acylcarnitines and other intermediates of mitochondrial β-oxidation and the urea cycle, branched-chain amino acids and biogenic amines
Time Frame
From baseline to week 12
Title
Metabolomics changes in urine
Description
Targeted and quantitative analysis by ultra-high-resolution liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ/MS). Analysis of specific families of metabolites selected from hypotheses generated by previous exploratory studies: changes in acylcarnitines and other intermediates of mitochondrial β-oxidation and the urea cycle, branched-chain amino acids and biogenic amines
Time Frame
From baseline to week 12
Secondary Outcome Measure Information:
Title
BMI (body mass index) changes
Description
Measured by body composition analysis
Time Frame
From baseline to to week 12
Title
Changes in insulin resistance
Description
Measured as HOMA-IR (homeostatic model assessment of insulin resistance)
Time Frame
From baseline to to week 12
Title
Changes in metabolic control
Description
Measured as HbA1c (glycated hemoglobin)
Time Frame
From baseline to to week 12
Title
Changes in Quality of Life: 36-Item Short Form Health Survey (SF-36) questionnaire
Description
The SF-36 has eight scaled scores: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The scores are weighted sums of the questions in each section. Scores range from 0 - 100, lower scores indicate more disability, and higher scores indicate less disability
Time Frame
From baseline to to week 12
Title
Changes in albuminuria
Description
Modifications in albuminuria, measured as albumin excretion rate (AER)
Time Frame
From baseline to to week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18-75. BMI 27-39.9 kg/m2. T2DM on treatment with metformin and inadequate metabolic control (defined as HbA1c≥6.5 -7%). Exclusion Criteria: Pregnancy (all women of child-bearing age, unless on treatment with contraceptive methods, will undergo a pregnancy test) Breastfeeding Intolerance/allergy to dapagliflozin. Treatment with antidiabetic drug other than metformin. Impaired kidney function: Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 (calculated using the CKD-EPI formula). Patients with established cardiovascular disease. Previous or current history of cancer of any kind. Uncontrolled hypertension (systolic blood pressure≥160 mmHg or diastolic blood pressure≥110 mmHg, despite adequate antihypertensive treatment). History of liver tumour or acute or chronic liver disease with impaired liver function: total bilirubin levels> 2.0 mg / dl or GOT/GPT levels three times higher than normal upper limit. Known HIV infection or active HBV or HCV infection. Other serious underlying diseases, which could affect the patient's ability to participate in the study. Reduced life expectancy (<12 months) due to advanced or terminal concomitant diseases. In addition, female patients of child-bearing age will be advised to use contraceptive methods during the study period, given the contraindication of dapagliflozin and metformin during pregnancy as per normal clinical practice.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jose Carlos Fernandez-Garcia, MD, PhD
Phone
+34951034016
Email
josecarlosfdezgarcia@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jose Carlos Fernandez-Garcia, MD, PhD
Organizational Affiliation
Virgen de la Victoria Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virgen de la Victoria University Hospital. Endocrinology Department
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jose Carlos Fernández García, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

SGLT-2 Inhibition, Metabolomics and Cardiovascular/Kidney Disease

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