Role of Linagliptin in Improving Renal Failure by Improving CD34+ Stem Cell Number, Function and Gene Expression in Renal Function Impaired Type 2 Diabetes Patients.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Cellular Markers
研究概览
简要总结
Type 2 diabetes is a national epidemic. Diabetes has undesirable effects on blood vessels which may contribute to heart disease. Endothelial Progenitor Cells (EPCs) are found in the blood. Research has shown that improving the survival of these special blood cells may decrease the harmful effects of diabetes on blood vessels and reduce or reverse heart disease. Linagliptin is an Food and Drug Administration (FDA) approved prescription medicine used along with insulin or with oral medications to lower blood sugar in people with Type 2 diabetes. It is in a class of diabetes medication called Dipeptidyl peptidase-4 (DPP-4) inhibitors. DPP-4 inhibitors have been shown to increase EPCs in patients with Type 2 diabetes.
Hypothesis: Both type 2 diabetes and Chronic Kidney Disease (CKD) are associated with poor stem cell number and function. Poor viability and function of EPCs in CKD and diabetes The investigators hypothesize that use of Linagliptin (along with Insulin) may help reduce cardiovascular risk by improving EPC survival and function above and beyond adequate glucose metabolism control
详细描述
Type 2 diabetes is a national epidemic with significant macro and microvascular complications. Insulin resistance in pre-diabetes and overt diabetes are associated with endothelial dysfunction.
A few studies indicate that stem cells particularly EPCs can act as a suitable bio-marker for monitoring cardiovascular morbidity. In this proposal the investigators suggest that EPCs or CD34 positive cells (defined as CD34/vascular endothelial growth factor receptor 2 (VEGFR2+) cells) can act as a suitable cellular biomarker for estimating and following endothelial dysfunction in early type 2 diabetes patients with CKD. EPCs have been shown to be dysfunctional in both CKD patients and type 2 Diabetes Mellitus (DM) patients.
Linagliptin (TRADJENTA) tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. No dose adjustment is recommended for patients with renal impairment.
EPCs have been used as a regenerative tool in ischemic myocardium and diabetic wound healing. Endothelial dysfunction with associated inflammation may be a consequence of excess intra-cellular super-oxide presence in a setting of diabetes which is a pro-oxidative stress condition ultimately leading to poor EPC function and senescence.
Though lifestyle modification has been proposed as a main stay for prevention and treatment of early type 2 diabetes, several new therapies for diabetes have been developed in recent years. Incretins and incretin mimetics appear to hold promise. Mechanism of positive effect of exercise and oral hypoglycemic agents can be very different.
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
- •Adults aged 30-70 years
- •Diagnosis of type 2 diabetes within the previous 15 years using criteria of the American Diabetes Association
- •Currently being treated with 1-2 grams/day of metformin, or insulin or both stably
- •Hemoglobin A1c (HbA1C) between 6.5% to 10.0% (both inclusive)
- •Body Mass Index (BMI) between 25 and 39.9 kg/m2 (both inclusive)
- •Chronic Kidney disease (CKD) Stages 1-3, Creatinine clearance (CrCl) less than 90 and more than 29
排除标准
- •Type 1 diabetes
- •History of Diabetic Ketoacidosis (DKA) or hyperosmolar nonketotic coma
- •Hemoglobinopathies with low hematocrit (Below 28 Units)
- •History of pancreatitis
- •History of cancer within the past 5 years (except basal cell carcinoma)
- •Previous cardiovascular or cerebrovascular event within 6 months of screening or active or clinically significant coronary and/or Peripheral Vascular Disease (PVD)
- •Statin use started in the last 3 month
- •Current use of oral or injectable anti-diabetic medication other than Metformin and insulin
- •Consistent use of steroids within the last 3 months
- •Any active wounds, or surgery within the past 3 months
- •Inflammatory disease, or the chronic use of anti-inflammatory drugs within the past 3 months
- •Untreated hyper/hypothyroidism
- •Contraindications to moderate exercise
- •Implanted devices that might interact with the tanita scale
- •Pre-existing liver disease and/or Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) > 2.5 times Under the Normal Limits (UNL)
- •Untreated Systolic blood pressure > 140 mmHg or diastolic blood pressure> 90 mmHg
- •Serum creatinine levels ≥ 2.0
- •CKD Stages 4 and 5 (estimated CrCl <30 mL/min)
- •Triglycerides > 450 mg/dL
- •Known allergies or hypersensitivities to Linagliptin or Dipeptidyl peptidase-4 (DDP-4) inhibitors
- •Treatment with cytochrome p450 (CYP 3A4) inhibitors
- •Women of child bearing age who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study
- •Prisoners or subjects that are involuntarily incarcerated
- •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
- •Additionally, patients who are active smokers, patients who are pregnant, nursing women, and post-menopausal women who are on hormone replacement therapy will be excluded.
研究组 & 干预措施
Placebo
Matching placebo 1 pill daily for 12 weeks
干预措施: Placebo (Drug)
Linagliptin
Linagliptin 5mg once daily for 12 weeks
干预措施: Linagliptin (Drug)
结局指标
主要结局
Cellular Markers
时间窗: Week 12 expression as a fold difference to Week 0
The investigators will use participants' peripheral blood derived CD34+ cells looking at number, function, and gene expression. Post Linagliptin will be compared to pre Linagliptin measurements. Here we report fold changes in protein populations as determined by ELISA.
Urinary Function Marker in CKD
时间窗: 12 weeks post beginning Linagliptin or placebo treatment
We measure using microalbumin/creatinine ratio provided from a random spot urine sample.
次要结局
- Fasting Lipid Profile(12 weeks post beginning Linagliptin or placebo treatment)
- Glycemic Control: Insulin(12 weeks post beginning Linagliptin or placebo treatment)
- Adiposity(12 weeks post beginning Linagliptin or placebo treatment)
- Pulse Wave Analysis(12 weeks post beginning Linagliptin or placebo treatment)
- Pulse Wave Velocity(12 weeks post beginning Linagliptin or placebo treatment)
- Resting Metabolic Rate (RMR)(12 weeks post beginning Linagliptin or placebo treatment)
- Serum Endothelial Inflammatory Markers(12 weeks post Linagliptin or Placebo treatment)
- Glycemic Control(12 weeks post beginning Linagliptin or placebo treatment)
- Glycemic Control: Fasting Glucose(12 weeks post beginning Linagliptin or placebo treatment)
- Estimation of Creatinine Clearance(12 weeks post beginning Linagliptin or placebo treatment)
研究者
Sabyasachi Sen
Associate Professor of Medicine
George Washington University