Clinical trial NCT03919656: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Metabolomics
Dapagliflozin
Lead sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Sponsor class: OTHER
First posted: 2019-04-18
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized in a 1:1 ratio
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Metabolomics changes in blood
timeFrame: From baseline to week 12
measure: Metabolomics changes in urine
timeFrame: From baseline to week 12
Secondary outcomes:
measure: BMI (body mass index) changes
timeFrame: From baseline to to week 12
measure: Changes in insulin resistance
timeFrame: From baseline to to week 12
measure: Changes in metabolic control
timeFrame: From baseline to to week 12
measure: Changes in Quality of Life: 36-Item Short Form Health Survey (SF-36) questionnaire
timeFrame: From baseline to to week 12
measure: Changes in albuminuria
timeFrame: From baseline to to week 12
Other outcomes:
Locations:
city: Malaga
country: Spain
facility: Virgen de la Victoria University Hospital. Endocrinology Department
Study officials:
affiliation: Virgen de la Victoria Hospital
name: Jose Carlos Fernandez-Garcia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: