The Effects of Natriuretic Peptide Augmentation on Cardiometabolic Health in Black Individuals (NAUTICAL)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Change in energy expenditure after natriuretic peptide augmentation
研究概览
简要总结
Black individuals are more likely to have decreased insulin sensitivity which results in a high risk for the development of cardiometabolic disease. The reasons for this are incompletely understood. Natriuretic peptides (NPs) are hormones produced by the heart that play a role in regulating the metabolic health of an individual. Low circulating level of NPs is an important contributor to increased risk for diabetes. The NP levels are relatively lower among Black individuals thus affecting their metabolic health and putting them at a higher risk for diabetes. This study aims to test the hypothesis that by augmenting NP levels using sacubitril/valsartan, among Black Individuals one can improve their metabolic health (as measured by insulin sensitivity & energy expenditure) and help establish the role of NPs in the underlying mechanism behind increased risk for cardiometabolic disease in these population.
详细描述
Black individuals are more likely to have a reduced insulin sensitivity which results in a greater risk for diabetes. However, the reasons for their decreased insulin sensitivity are not clearly understood. Natriuretic peptides (NPs) are hormones produced by the heart that is known to have a wide range of favorable metabolic effects. Studies indicate that lower NP levels are associated with a decreased insulin sensitivity and this may be causally related to the development of diabetes.
Evidence suggests that Black individuals have low levels of NPs. Increased clearance of NPs by neprilysin, an NP degrading enzyme, contributes to the low levels of NP among Black individuals. Since NPs play an important role in the regulation of insulin sensitivity and energy expenditure, one can infer that relatively low NP levels are an important biological contributor to the high prevalence rates of cardiometabolic disease in African Americans.
Sacubitril/valsartan is an FDA-approved inhibitor of neprilysin that augment NP levels. NP augmentation using sacubitril/valsartan has been shown to improve insulin sensitivity and lipid metabolism in a small clinical trial among obese White individuals. It can be postulated that NP augmentation in populations with relatively low NP levels will help in improving their metabolic health. Improvement in the metabolic health following NP augmentation will also help us to outline the relationship between the NP system and the risk of cardiometabolic disease among Black individuals.
We hypothesize that NP augmentation among Black individuals will show an improvement in their metabolic health as measured by insulin sensitivity and energy expenditure. We hypothesize that African American individuals will show an improvement in their insulin sensitivity and their resting & exercise energy expenditure after treatment with sacubitril/valsartan versus valsartan alone.
Our study will have the following aims. The first aim is to assess the change in the insulin sensitivity after NP augmentation therapy (using sacubitril/valsartan) as compared with NP neutral therapy (using valsartan) among Black individuals. We will measure the change in insulin sensitivity (assessed using IVGTT) after 12 weeks of intervention. We will also assess the change in NP levels (a marker of NP augmentation) & cyclic guanylate monophosphate (cGMP) levels after intervention and evaluate their relationship with the change in insulin sensitivity.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults: Age more than or equal to 18 years of age
- •Self-identified race/ethnicity as African-American or Black
- •Blood pressure: 120-160/80-100 mmHg
排除标准
- •Women who are pregnant or breastfeeding or who can become pregnant and not practicing an acceptable method of birth control during the study (including abstinence)
- •Have any past or present history of cardiovascular diseases (stroke, myocardial infarction, heart failure, transient ischemic attack, angina, or cardiac arrhythmia)
- •BP more than 160/100 mmHg
- •BMI >45 kg/m2
- •History of diabetes or fasting plasma glucose >=126 mg/dL or HbA1C>=6.5%
- •History of angioedema
- •Current or past (<12 months) history of smoking
- •Estimated GFR < 60 ml/min/1.73 m2; albumin-creatinine ratio ≥30 mg/g
- •Hepatic Transaminase (AST and ALT) levels >3x the upper limit of normal
- •Significant psychiatric illness or seizure disorder
- •More than 2 Alcoholic drinks daily
- •Anemia (men, Hct < 38%, Hb<13 g/dL; women, Hct <36%, Hb <12 g/dL)
- •Inability to exercise on a treadmill
研究组 & 干预措施
Sacubitril/Valsartan
We will enroll 100 adult Black individuals. Each participant will take the assigned dose of medication twice daily for 12 weeks. We evaluate insulin sensitivity and energy expenditure at baseline and after 12 weeks of intervention.
干预措施: Exercise capacity VO2 maximum determination (Other)
Sacubitril/Valsartan
We will enroll 100 adult Black individuals. Each participant will take the assigned dose of medication twice daily for 12 weeks. We evaluate insulin sensitivity and energy expenditure at baseline and after 12 weeks of intervention.
干预措施: Sacubitril, Valsartan 97-103 mg Oral Tablet (Drug)
Sacubitril/Valsartan
We will enroll 100 adult Black individuals. Each participant will take the assigned dose of medication twice daily for 12 weeks. We evaluate insulin sensitivity and energy expenditure at baseline and after 12 weeks of intervention.
干预措施: Intravenous Glucose Tolerance Test (Other)
Sacubitril/Valsartan
We will enroll 100 adult Black individuals. Each participant will take the assigned dose of medication twice daily for 12 weeks. We evaluate insulin sensitivity and energy expenditure at baseline and after 12 weeks of intervention.
干预措施: Standardized Meals (Dietary Supplement)
Valsartan
We will enroll 100 adult Black individuals. Each participant will take the assigned dose of medication twice daily for 12 weeks. We evaluate insulin sensitivity and energy expenditure at baseline and after 12 weeks of intervention.
干预措施: Intravenous Glucose Tolerance Test (Other)
Valsartan
We will enroll 100 adult Black individuals. Each participant will take the assigned dose of medication twice daily for 12 weeks. We evaluate insulin sensitivity and energy expenditure at baseline and after 12 weeks of intervention.
干预措施: Standardized Meals (Dietary Supplement)
Valsartan
We will enroll 100 adult Black individuals. Each participant will take the assigned dose of medication twice daily for 12 weeks. We evaluate insulin sensitivity and energy expenditure at baseline and after 12 weeks of intervention.
干预措施: Exercise capacity VO2 maximum determination (Other)
Valsartan
We will enroll 100 adult Black individuals. Each participant will take the assigned dose of medication twice daily for 12 weeks. We evaluate insulin sensitivity and energy expenditure at baseline and after 12 weeks of intervention.
干预措施: Valsartan 160 mg (Drug)
结局指标
主要结局
Change in energy expenditure after natriuretic peptide augmentation
时间窗: 12 weeks
An assessment of the resting energy expenditure will be done at baseline and after 12 weeks of pharmacological intervention.
Change in insulin sensitivity after natriuretic peptide augmentation
时间窗: 12 weeks
An assessment of the insulin sensitivity will be done at baseline and after 12 weeks of pharmacological intervention.
次要结局
- Change in HOMA-IR(12 weeks)
- Change in peak oxygen consumption after 12 weeks of pharmacological intervention.(12 weeks)
- Change in measures of insulin sensitivity(12 weeks)
- Change in HBA1c levels(12 weeks)
- Correlation of change in B-type natriuretic peptide levels with change in insulin sensitivity after 12 weeks of pharmacological intervention.(12 weeks)
- Change in post-meal increase in GLP-1 levels(12 weeks)
- Change in measures of body mass index(12 weeks)
- Change in total cholesterol levels(12 weeks)
- Change in HDL-C levels(12 weeks)
- Correlation of change in MR-pro atrial natriuretic peptide levels with change in insulin sensitivity after 12 weeks of pharmacological intervention.(12 weeks)
- Correlation of change in MR-pro atrial natriuretic peptide levels with change in energy expenditure after 12 weeks of pharmacological intervention.(12 weeks)
- Correlation of change in NT-pro B-type natriuretic peptide levels with change in energy expenditure after 12 weeks of pharmacological intervention.(12 weeks)
- Change in exercise energy expenditure after 12 weeks of pharmacological intervention.(12 weeks)
- Change in fasting GLP-1 levels(12 weeks)
- Change in measures of waist circumference(12 weeks)
- Impact of Natriuretic Peptide Genotype on Study Endpoints(12 weeks)
- Change in natriuretic peptide levels(12 weeks)
- Change in fasting insulin levels(12 weeks)
- Change in measures of hip circumference(12 weeks)
- Change in measures of adipose tissue mass(12 weeks)
- Change in LDL-C levels(12 weeks)
- Change in triglyceride levels(12 weeks)
- Change in fasting blood glucose levels(12 weeks)
- Correlation of change in B-type natriuretic peptide levels with change in resting energy expenditure after 12 weeks of pharmacological intervention.(12 weeks)
- Correlation of change in NT-pro B-type natriuretic peptide levels with change in insulin sensitivity after 12 weeks of pharmacological intervention.(12 weeks)
研究者
Pankaj Arora, MD
Associate Professor, Division of Cardiovascular Disease, Department of Medicine
University of Alabama at Birmingham