Cardio-Protective of Effect of Saxagliptin and Dapagliflozin Combination on Endothelial Progenitor Cells in Patients With Type 2 Diabetes
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- CD 34+ Cell Migratory Function
研究概览
简要总结
The Investigator hypothesize that Dapagliflozin will improve EPC number and function AND Saxagliptin in addition to Dapagliflozin (additive effect) may improve EPC number and function even more than Dapa alone, compared to placebo.
The Investigator propose a 3-arm randomized, parallel group, longitudinal study of 16-week intervention duration. Participants will be randomized to 3 groups:
Group A: Dapa (10 mg) + Saxa Placebo, Enroll n=15, retain n=12 Group B: Dapa (10 mg) + Saxa (5 mg), Enroll n=15, retain n=12 Group C: Dapa Placebo + Saxa Placebo, Enroll n=15, retain n=12
详细描述
The Investigator hypothesize that Dapagliflozin will improve EPC number and function AND Saxagliptin in addition to Dapagliflozin may have an additive effect to improve EPC number and function even more than Dapa alone, compared to placebo.
In this proposal the investigator plan to conduct a placebo matched study with type 2 diabetes subjects on any doses of metformin or Insulin or a combination of both and has no history of DPP4 ( Dipeptidyl Peptidase-4) DPP4 inhibitor, incretin mimetic or SGLT2 inhibitor intake history. Participants will have known macrovascular complications (such as Cardiovascular Disease (CVD), Cerebrovascular Accident (CVA), and Peripheral Vascular Disease (PVD).
3 STUDY OBJECTIVES
PRIMARY OBJECTIVE:
CELLULAR BIOMARKER OF ENDOTHELIUM
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand the study, and provide a signed & dated informed consent.
- •Diagnosis of Type 2 diabetes mellitus using criteria of the American Diabetes Association.
- •30-70 years old.
- •HbA1C 7 to 10%, both inclusive
- •BMI of 25 - 39.9 kg/m2 both inclusive.
- •Taking a stable dose (for 12 weeks) of Metformin (any dosage) and/or Insulin (any dosage) for the treatment of T2DM
- •Patients with current Cardiovascular Disease (CVD) in tye 2 diabetes patients, defined by ≥ 1 of the following:
- •MI >2 months prior
- •Multivessel CAD
- •Angina (intermittent or chronic)
- •Single vessel CAD with positive stress test or UA hospitalization in prior year
- •UA >2 months prior and evidence of CAD
- •Stroke >2 months prior
- •Occlusive PAD
- •Proteinuria of more than 30mg/dl
排除标准
- •Planned CV surgery or angioplasty in 1 month
- •Prior surgery with chronic malabsorption (eg, bariatric) in prior 1 year
- •Diagnosis of Type 1 diabetes mellitus
- •History of GAD antibody positive status
- •Uncontrolled Inflammatory Disease/Inflammatory drug use. **Evaluated by PI on case-by-case basis**
- •Recent history of diabetic keto-acidosis in the past 3months, or recurrent history of diabetic ketoacidosis (≥ 3 times)
- •Active bladder cancer
- •Active wounds (e.g. Diabetic ulcers) or recent surgery within 1 month
- •Untreated hyper/hypothyroidism
- •Women of child bearing potential who are not willing to use a contraceptive method to avoid pregnancy for the 16 weeks of study duration
- •Women who are pregnant or breastfeeding
- •Implanted devices (eg. Pacemaker) that may interact with Tanita scale
- •Any other clinical condition that would jeopardize patients safety while participating in this clinical trial Concomitant Medications
- •Taking any other oral anti-diabetic agent other than Metformin and/or Insulin for their treatment of T2DM
- •Beginning statin medications in the past 1 month or change in statin dose in the past 1 month
- •Use of consistent long-term steroid medication (oral, inhaled, injected) within the last 1 month
- •Treatment with a strong cytochrome P450 3A4 (CYP34A) or P-gp inducer (ie. Rifampin)
- •Subjects with a history of any serious hypersensitivity reaction to Dapagliflozin / Saxagliptin or another SGLT-2 inhibitor/ DPP4 inhibitor Laboratory Findings
- •Uncontrolled hyperglycemia, defined as a fasting glucose >240 mg/dL (>13.3 mmol/L) at screening.
- •Liver disease with ALT, AST or ALP x3 ULN
- •eGFR < 60 mL/min/1.73 m2 by MDRD equation in the past 3 months
- •Clinically significant RBC disorders such as hemoglobinopathies
- •Serum creatinine levels ≥1.8 mg/dL with estimated eGFP < 60 mL/min
- •Triglycerides > 450 mg/dL
- •Baseline Hematuria (judged by a urinalysis dipstick at screening) Social History
- •Active smokers
- •Chronic or persistent alcohol or drug abuse
- •Prisoners or subjects who are involuntarily incarcerated
- •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg. infectious disease) illness
- •Participation in another trial with an investigational drug within 30 days prior to informed consent
研究组 & 干预措施
Group A Dapa
Dapagliflozin 10 mg + Saxagliptin Placebo
干预措施: Dapagliflozin 10mg (Drug)
Group B DapaSaxa
Dapagliflozin 10mg + Saxagliptin 5mg
干预措施: Dapagliflozin 10mg (Drug)
Group B DapaSaxa
Dapagliflozin 10mg + Saxagliptin 5mg
干预措施: Saxagliptin 5mg (Drug)
Placebo
Placebo Oral Tablet
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
CD 34+ Cell Migratory Function
时间窗: 16 weeks
Proportion of cells that migrate through SDF1a in a transwell assay. This proportion is represented as a migratory rating scale from 0-1, with 1 being 100% of cells migrate. A larger value indicates better migratory function of the CD34+ cells.
次要结局
- Urine Exosome Assay(16 Weeks)
- Arterial Stiffness(Week 16)
- Renal Function(16 Weeks)
- CD 34+ Cell Gene Expression(16 weeks from visit 1)
- Arterial Stiffness - Augmentation Index(16 Weeks)
- CD 34+ Cell Fraction(16 weeks)
- Blood Biochemistries(16 Weeks)
- Arterial Stiffness - Augmentation Pressure(16 Weeks)
研究者
Sabyasachi Sen
Associate Professor, Dept. of Medicine (Division of Endocrinology)
George Washington University