Racial Differences in the Natriuretic Peptide Response to Exercise and Beta-blockers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Change in Plasma BNP After 6-weeks of Beta-Blocker
研究概览
简要总结
The purpose of the study is to understand the origins of differential response to beta-blockers in African-Americans and may provide insight regarding racial differences in cardiovascular risk.
详细描述
The heart is an endocrine organ. The natriuretic peptides are hormones produced in the heart and are secreted in response to increased wall stress in atria and ventricles. The principal circulating NPs are Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP). The endocrine actions of NPs are natriuresis and dilatation of peripheral arteries.
The NPs concentrations are elevated in heart failure (HF) and hypertension (HTN) due to volume and pressure overload. Therefore, NPs are used as diagnostic and prognostic markers in heart failure. However, NPs role in healthy individuals is not known.
Previous studies have shown that reduced NP levels are associated with a greater risk of HTN. Moreover, African-Americans have lower resting NP levels than Caucasians. We hypothesize that relative NP deficiency in African American compared to Caucasian has the potential to contribute to increase risk of all-cause mortality, HTN, HF and its sequelae.
Evidence from multiple clinical trials has positioned beta-blockers as a standard heart failure therapy. Beta-blocker therapy leads to increased NP levels and suppression of Renin-aldosterone-angiotensin system (RAAS) system. Suppression of renin levels by beta-blockers has been shown as a potential mechanism of benefit in HF. However, study shows that beta-blockers are less effective in African-Americans compared to Caucasians in HF treatment. So, the investigators have proposed a pilot study to look for race-based differences in the NP and RAAS response to metoprolol in healthy individuals.
Additionally, exercise has been reported to increase NP levels. ANP increases more than BNP with exercise. But there is no data of NP changes in African-American with exercise. So the investigators have proposed a sub-study of race-based difference in ANP and BNP response to exercise.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 to 40 years
- •Blood pressure less than 140/90 mm Hg
- •Able to perform exercise capacity test
- •BMI 18-30 kg/m2
- •Willing to adhere to study drug
排除标准
- •History of cardiovascular disease or use of medications for CVD
- •History of hypertension or use of BP lowering medications
- •Blood pressure less than 100/60 mm Hg
- •Heart rate less than 60 beats/min
- •Depression
- •Diabetes or use of anti-diabetic medications
- •Renal disease (eGFR < 60ml/min/1.73m2)
- •Current or prior smokers
- •Pregnant or use of Hormone Replacement Therapy (HRT) or oral contraceptives (OCP) or steroids
研究组 & 干预措施
Black Participants
Healthy lean (BMI 18-25 kg/m2) African-American participants will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will perform exercise capacity VO2 max determination test, followed by 3 days of standardized meals and exercise challenge test. After exercise challenge test, all the participants will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day.
干预措施: Exercise capacity VO2 max determination (Other)
Black Participants
Healthy lean (BMI 18-25 kg/m2) African-American participants will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will perform exercise capacity VO2 max determination test, followed by 3 days of standardized meals and exercise challenge test. After exercise challenge test, all the participants will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day.
干预措施: Standardized meals (Dietary Supplement)
Black Participants
Healthy lean (BMI 18-25 kg/m2) African-American participants will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will perform exercise capacity VO2 max determination test, followed by 3 days of standardized meals and exercise challenge test. After exercise challenge test, all the participants will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day.
干预措施: Exercise challenge (Other)
Black Participants
Healthy lean (BMI 18-25 kg/m2) African-American participants will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will perform exercise capacity VO2 max determination test, followed by 3 days of standardized meals and exercise challenge test. After exercise challenge test, all the participants will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day.
干预措施: Metoprolol Succinate ER (Drug)
White Participants
Healthy lean (BMI 18-25 kg/m2) white participants will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will perform exercise capacity VO2 max determination test, followed by 3 days of standardized meals and exercise challenge test. After exercise challenge test, all the participants will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day.
干预措施: Exercise capacity VO2 max determination (Other)
White Participants
Healthy lean (BMI 18-25 kg/m2) white participants will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will perform exercise capacity VO2 max determination test, followed by 3 days of standardized meals and exercise challenge test. After exercise challenge test, all the participants will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day.
干预措施: Standardized meals (Dietary Supplement)
White Participants
Healthy lean (BMI 18-25 kg/m2) white participants will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will perform exercise capacity VO2 max determination test, followed by 3 days of standardized meals and exercise challenge test. After exercise challenge test, all the participants will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day.
干预措施: Exercise challenge (Other)
White Participants
Healthy lean (BMI 18-25 kg/m2) white participants will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will perform exercise capacity VO2 max determination test, followed by 3 days of standardized meals and exercise challenge test. After exercise challenge test, all the participants will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day.
干预措施: Metoprolol Succinate ER (Drug)
结局指标
主要结局
Change in Plasma BNP After 6-weeks of Beta-Blocker
时间窗: 6 weeks
Mean percentage change in plasma BNP concentrations in response to 6 weeks of Beta-Blocker between Black participants and White participants
Change in Plasma NT-proBNP After 6-weeks of Beta-Blocker
时间窗: 6 weeks
Mean percentage change in plasma NT-proBNP concentrations in response to 6 weeks of Beta-Blocker between Black participants and White participants
Change in Plasma MR-proANP After 6-weeks of Beta-Blocker
时间窗: 6 weeks
Mean percentage change in plasma MR-proANP concentrations in response to 6 weeks of Beta-Blocker between Black participants and White participants
次要结局
- Change in Plasma BNP After Standardized Exercise Challenge(Mean percentage change in plasma BNP concentrations from baseline to 20 minutes post-exercise (immediately after exercise))
- Change in Plasma NT-proBNP After Standardized Exercise Challenge(Mean percentage change in plasma NT-proBNP concentrations from baseline to 20 minutes post-exercise (immediately after exercise))
- Change in Plasma MR-proANP After Standardized Exercise Challenge(Mean percentage change in plasma MR-proANP concentrations from baseline to 20 minutes post-exercise (immediately after exercise))
研究者
Pankaj Arora, MD
Associate Professor
University of Alabama at Birmingham