Therapeutic Strategies for Microvascular Dysfunction in Type 1 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Microvascular blood volume (MBV)
研究概览
简要总结
The investigators will test the hypothesis that, in adults with type 1 diabetes (T1D), glucagon-like peptide-1 receptor agonism (GLP-1RA, i.e. dulaglutide) enhances insulin-mediated skeletal muscle microvascular perfusion via attenuating endothelial oxidative stress and thereby improving endothelial function.
详细描述
In this study, 47 (n=32 needed to complete) adult participants with type 1 diabetes will be randomized (1:1) to 14-weeks of one of 2 interventions: 1) dulaglutide, 2) placebo.
Participants will undergo two study admissions at baseline and 14 weeks. Prior to each admission, participants will wear a continuous glucose monitor (Dexcom G6 Professional) for 10 days to assess glycemic variability (GV). Prior to admissions, they will undergo cardiorespiratory fitness testing. On study admission days, participants will undergo an antecubital vein endothelial cell biopsy prior to commencing vascular testing. From the harvested endothelial cells, the investigators will quantify endothelial cell reactive oxygen species (ROS) and gene expression relevant to insulin-mediated endothelial function. Vascular testing will include contrast enhanced ultrasound of quadriceps muscle to determine microvascular blood volume (MBV). The investigators will also measure brachial artery flow mediated dilation (FMD). Quadriceps skeletal muscle oxygenation (HHb) will also be measured. These vascular and muscle oxygenation measurements will be conducted before and after a 120-minute euglycemic insulin clamp which will measure insulin sensitivity based on glucose infusion rate (GIR).
This randomized, placebo-controlled study will assess whether GLP-1 receptor agonism with dulaglutide or exercise training improves insulin-mediated skeletal muscle microvascular perfusion. The investigators will assess for predictive relationships between microvascular perfusion and cardiorespiratory fitness (VO2max), insulin sensitivity (GIR), endothelial reactive oxygen species (ROS), and glycemic variability (GV).
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
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Participants randomized to dulaglutide or placebo and study personnel who analyze data and instruct patients regarding insulin adjustments will be blinded to treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of type 1 diabetes, duration > 5 years
- •Age 18-40 years
- •HbA1c < 8.5%
- •BMI 19-34.9 kg/m2
- •Using insulin for diabetes treatment only (multiple daily injections or insulin pump with or without sensor augmentation)
- •On stable regimen of non-diabetic medications for the last 6 months
- •All screening labs within normal limits or not clinically significant - English or Spanish speaking
排除标准
- •Pregnancy or currently breastfeeding
- •Smoking history within 6 months
- •History of microvascular (microalbuminuria, retinopathy, neuropathy) or macrovascular diabetes complications (coronary artery disease, stroke, peripheral vascular disease) as well as clinically significant cardiac arrhythmias or conduction disorders
- •Taking vasoactive medications (i.e. calcium channel blockers, angiotensin-converting enzyme or renin inhibitors, angiotensin-receptor blockers, nitrates, alpha-blockers).
- •Known hypersensitivity to perflutren (contained in Definity© contrast)
- •Screening O2 saturation <90%
- •Musculoskeletal condition preventing participation in exercise testing or exercise training
- •Acute or unstable disease other than T1D
- •Hypoglycemia unawareness
- •History of gastroparesis, severe gastroesophageal reflux, pancreatitis, personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
- •Anemia (hemoglobin <12 g/dL in women, hemoglobin <13 g/dL in men), eosinophilia (absolute eosinophil count >500 cells/microliter) leukopenia (total white blood cells <4,000 cells/microliter)
- •Diabetic ketoacidosis (DKA) on presentation to screening visits or study admission days
- •Hospital admission for DKA within 1 year
研究组 & 干预措施
Placebo
Saline subcutaneous injection, volume matched to dulaglutide, i.e. 0.5 mL weekly for 14 weeks
干预措施: Placebo (Drug)
Dulaglutide
Dulaglutide (0.75 mg/0.5 mL weekly for 2 weeks, then 1.5 mg/0.5 mL weekly for 12 weeks) subcutaneous injection
干预措施: Dulaglutide (Drug)
结局指标
主要结局
Microvascular blood volume (MBV)
时间窗: At baseline and after 14 weeks of treatment.
Insulin mediated change in muscle microvascular blood volume (MBV). A measure of microvascular nitric oxide dependent endothelial function
次要结局
- Brachial artery flow mediated dilation (FMD)(At baseline and after 14 weeks of treatment)
- Glucose infusion rate (GIR)(At baseline and after 14 weeks of treatment)
- Cardiorespiratory fitness, maximum consumption of oxygen (VO2max)(At baseline and after 14 weeks of treatment)
- Skeletal muscle oxygenation, deoxyhemoglobin (HHb)(At baseline and after 14 weeks of treatment. Measured before and after insulin clamp.)
研究者
Kaitlin Love
Principal Investigator
AdventHealth Translational Research Institute