Race, Natriuretic Peptides and Physiological Perturbations

Phase 2

Completed

• Conditions: Pre Hypertension; Healthy
• Interventions: Other: Exercise capacity VO2 max determination; Dietary Supplement: Standardized meals; Other: Exercise challenge; Drug: Metoprolol Succinate ER

• Registration Number: NCT03070184
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

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.

Detailed Description

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.

40 African-American and 40 Caucasians normotensive or pre-hypertensive (healthy) individuals will be enrolled.

Study Timeline

• Study First Submitted: 2017-02-28
• Study First Submitted QC: 2017-02-28
• Study First Posted: 2017-03-03
• Study Start: 2017-04-30
• Primary Completion: 2023-12-31
• Study Completion: 2024-04-30
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-09
• Last Update Posted: 2024-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• 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

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Exclusion Criteria

• 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Black Participants	Metoprolol Succinate ER	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.
White Participants	Metoprolol Succinate ER	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.
Black Participants	Standardized meals	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.
White Participants	Standardized meals	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.
Black Participants	Exercise capacity VO2 max determination	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.
Black Participants	Exercise challenge	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.
White Participants	Exercise capacity VO2 max determination	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.
White Participants	Exercise challenge	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.

Primary Outcome Measures

Name	Time	Method
Change in Plasma BNP After 6-weeks of Beta-Blocker	6 weeks	Percent increase 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	About 3 hours on the exercise challenge visit day after consuming study meals for 3 days	Percent increase 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	6 weeks	Percent increase in plasma MR-proANP concentrations in response to 6 weeks of Beta-Blocker between Black participants and White participants

Secondary Outcome Measures

Name	Time	Method
Change in Plasma BNP After Exercise	After 20 minutes of the Standardized Exercise Challenge at 70% of their maximal oxygen uptak	Percent increase in plasma BNP concentrations in response to exercise
Change in Plasma MR-proANP After Exercise	After 20 minutes of the Standardized Exercise Challenge at 70% of their maximal oxygen uptake	Percent increase in plasma MR-proANP concentrations in response to exercise
Change in Plasma NT-proBNP After Exercise	After 20 minutes of the Standardized Exercise Challenge at 70% of their maximal oxygen uptake	Percent increase in plasma NT-proBNP concentrations in response to exercise

Trial Locations

Locations (1)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States