SGLT-2 Inhibition and Cardiovascular Disease. Metabolomics Study of Potential Factors Involved in Cardio- and Nephroprotection
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Metabolomics changes in blood
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
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
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI 27-39.9 kg/m
- •T2DM on treatment with metformin and inadequate metabolic control (defined as HbA1c≥6.5 -7%).
排除标准
- •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.
研究组 & 干预措施
Dapagliflozin
Dapagliflozin 10 mg daily (orally)
干预措施: Dapagliflozin 10 mg (Drug)
Placebo
Matching placebo for dapagliflozin daily (orally). Does not contain active ingredient
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Metabolomics changes in blood
时间窗: 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
时间窗: 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
次要结局
- BMI (body mass index) changes(From baseline to to week 12)
- Changes in insulin resistance(From baseline to to week 12)
- Changes in Quality of Life: 36-Item Short Form Health Survey (SF-36) questionnaire(From baseline to to week 12)
- Changes in albuminuria(From baseline to to week 12)
- Changes in metabolic control(From baseline to to week 12)