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SGLT-2 Inhibition, Metabolomics and Cardiovascular/Kidney Disease

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ClinicalTrials.gov Identifier: NCT03919656
Recruitment Status : Not yet recruiting
First Posted : April 18, 2019
Last Update Posted : April 23, 2019
Sponsor:
Information provided by (Responsible Party):
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

Tracking Information
First Submitted Date  ICMJE April 11, 2019
First Posted Date  ICMJE April 18, 2019
Last Update Posted Date April 23, 2019
Estimated Study Start Date  ICMJE May 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
  • Metabolomics changes in blood [ Time Frame: From baseline to week 12 ]
    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 [ Time Frame: From baseline to week 12 ]
    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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03919656 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2019)
  • BMI (body mass index) changes [ Time Frame: From baseline to to week 12 ]
    Measured by body composition analysis
  • Changes in insulin resistance [ Time Frame: From baseline to to week 12 ]
    Measured as HOMA-IR (homeostatic model assessment of insulin resistance)
  • Changes in metabolic control [ Time Frame: From baseline to to week 12 ]
    Measured as HbA1c (glycated hemoglobin)
  • Changes in Quality of Life: 36-Item Short Form Health Survey (SF-36) questionnaire [ Time Frame: From baseline to to week 12 ]
    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 [ Time Frame: From baseline to to week 12 ]
    Modifications in albuminuria, measured as albumin excretion rate (AER)
Original Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
  • BMI (body mass index) changes [ Time Frame: From baseline to to week 12 ]
    Measured by body composition analysis
  • Changes in insulin resistance [ Time Frame: From baseline to to week 12 ]
    Measured as HOMA-IR (homeostatic model assessment of insulin resistance)
  • Changes in metabolic control [ Time Frame: From baseline to to week 12 ]
    Measured as HbA1c (glycated hemoglobin)
  • Changes in Quality of Life: SF-36 questionnaire [ Time Frame: From baseline to to week 12 ]
    SF-36 questionnaire
  • Changes in albuminuria [ Time Frame: From baseline to to week 12 ]
    Modifications in albuminuria, measured as albumin excretion rate (AER)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SGLT-2 Inhibition, Metabolomics and Cardiovascular/Kidney Disease
Official Title  ICMJE SGLT-2 Inhibition and Cardiovascular Disease. Metabolomics Study of Potential Factors Involved in Cardio- and Nephroprotection
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Patients will be randomized in a 1:1 ratio
Masking: Double (Participant, Investigator)
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
Primary Purpose: Basic Science
Condition  ICMJE Type 2 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Dapagliflozin 10 mg
    Dapagliflozin 10 mg daily in a green, plain, diamond shaped, film coated tablet (orally)
    Other Name: Farxiga 10 mg
  • Drug: Placebo Oral Tablet
    Green, plain, diamond shaped, film coated tablet (orally). Does not contain active ingredient
Study Arms  ICMJE
  • Experimental: Dapagliflozin
    Dapagliflozin 10 mg daily (orally)
    Intervention: Drug: Dapagliflozin 10 mg
  • Placebo Comparator: Placebo
    Matching placebo for dapagliflozin daily (orally). Does not contain active ingredient
    Intervention: Drug: Placebo Oral Tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 15, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jose Carlos Fernandez-Garcia, MD, PhD +34951034016 josecarlosfdezgarcia@hotmail.com
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03919656
Other Study ID Numbers  ICMJE FIM-DAPA-2018-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Study Sponsor  ICMJE Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jose Carlos Fernandez-Garcia, MD, PhD Virgen de la Victoria Hospital
PRS Account Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP