The Role of the Renin-Angiotensin-Aldosterone System in Adiposity, Blood Pressure and Glucose Metabolism Among African Americans: Pilot Study
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Change from Baseline to 26 weeks in β-cell function (first-phase insulin secretion)
研究概览
简要总结
The primary objective is to examine the impact of the Renin-Angiotensin-Aldosterone System (RAAS) blockade with medications (valsartan) or RAAS and neprilysin inhibition (valsartan/sacubitril) vs. placebo on changes in blood sugar and insulin secretion from the pancreas over 26 weeks assessed with glucose clamp studies among African Americans (AAs) with impaired glucose tolerance.
The investigators hypothesize that combined RAAS/neprilysin inhibition will lead to greater improvement in insulin release from the pancreas and improved blood sugar compared to RAAS inhibition alone among AAs with impaired glucose tolerance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Blinding
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •African Americans aged 18-65 years old with a history of impaired fasting glucose, impaired glucose tolerance, hemoglobin A1c 5.7-6.4% or other risk factors for diabetes including metabolic syndrome, family history of type 2 diabetes in the parents or siblings or history of gestational diabetes will be invited to attend a formal screening visit. Participants with impaired glucose tolerance defined as 2-hour plasma glucose 140-199 mg/dl after a fasting 75-g oral glucose tolerance test and who meet other enrollment criteria will be enrolled.
排除标准
- •Type 2 Diabetes (American Diabetes Association Criteria)
- •Hypertension with systolic blood pressure (SBP) > 150 mmHg or diastolic blood pressure (DBP) > 100 mmHg or taking anti-hypertensive medications
- •SBP < 100 mmHg or DBP < 60 mmHg
- •Pharmacologic treatment with statins, β-Blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, renin inhibitors, and/or mineralocorticoid antagonists
- •Steroid use
- •Hyperkalemia (Potassium > 5.0 milliequivalent/L)
- •Abnormal renal function tests: Glomerular Filtration Rate calculated using the Chronic Kidney Disease Epidemiology Equation < 60 ml/min/1.73 m²
- •Treatment with oral hypoglycemic medications,
- •Use of antipsychotic medications or severe psychiatric disorders (severe mental illness)
- •Severe Psychiatric Disorders:
- •Schizophrenia
- •Paranoid and other psychotic disorders
- •Bipolar disorders (hypomanic, manic, depressive, and mixed)
- •Major depressive disorders (single episode or recurrent)
- •Schizoaffective disorders (bipolar or depressive)
- •Pervasive developmental disorders
- •Obsessive-compulsive disorders
- •Depression in childhood and adolescence
- •Panic disorder
- •Post-traumatic stress disorders (acute, chronic, or with delayed onset)
- •Bulimia Nervosa
- •Anorexia Nervosa
- •History of, or planned, bariatric surgery,
- •Weight loss > 5% over the previous 6 months,
- •Pregnancy, planning to conceive a child in the next 9 months, or progesterone based contraception and unable to switch to non-progesterone based contraception,
- •Previous or current diagnosis of cardiac structural and functional abnormalities, history or current diagnosis of heart failure (New York Heart Association classes II-IV), history of myocardial infarction, coronary bypass surgery, or percutaneous coronary intervention during the 6 months prior to screening,
- •History of angioedema, or known hypersensitivity to study drugs.
研究组 & 干预措施
Valsartan
Valsartan 160 mg twice daily for 26 weeks
干预措施: Valsartan 160mg (Drug)
Sacubitril/Valsartan
Sacubitril/Valsartan (97/103 mg) twice daily for 26 weeks
干预措施: Sacubitril-Valsartan Tab 97-103 MG (Drug)
Placebo
placebo (+/- amlodipine 2.5-5 mg twice daily if high blood pressure)
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Change from Baseline to 26 weeks in β-cell function (first-phase insulin secretion)
时间窗: 26 weeks
β-cell function will be assessed by first-phase insulin secretion, calculated as the mean insulin concentration (uIU/mL) over 10 minutes during the hyperglycemic clamp.
次要结局
- Change in Central Aortic Pressure (mmHg) from Baseline to 26 weeks(26 weeks)
研究者
Joshua Joseph, MD
Assistant Professor of Medicine
Ohio State University