Clinical trial NCT03070184: Race, Natriuretic Peptides and Physiological Perturbations
Official title: Racial Differences in the Natriuretic Peptide Response to Exercise and Beta-blockers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy
Pre Hypertension
Keywords: Racial differences
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-03-03
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Change in Plasma BNP After 6-weeks of Beta-Blocker
timeFrame: 6 weeks
measure: Change in Plasma NT-proBNP After 6-weeks of Beta-Blocker
timeFrame: 6 weeks
measure: Change in Plasma MR-proANP After 6-weeks of Beta-Blocker
timeFrame: 6 weeks
Secondary outcomes:
measure: Change in Plasma BNP After Standardized Exercise Challenge
timeFrame: Mean percentage change in plasma BNP concentrations from baseline to 20 minutes post-exercise (immediately after exercise)
measure: Change in Plasma NT-proBNP After Standardized Exercise Challenge
timeFrame: Mean percentage change in plasma NT-proBNP concentrations from baseline to 20 minutes post-exercise (immediately after exercise)
measure: Change in Plasma MR-proANP After Standardized Exercise Challenge
timeFrame: Mean percentage change in plasma MR-proANP concentrations from baseline to 20 minutes post-exercise (immediately after exercise)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Pankaj Arora, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Davis ME, Richards AM, Nicholls MG, Yandle TG, Frampton CM, Troughton RW. Introduction of metoprolol increases plasma B-type cardiac natriuretic peptides in mild, stable heart failure. Circulation. 2006 Feb 21;113(7):977-85. doi: 10.1161/CIRCULATIONAHA.105.567727. Epub 2006 Feb 13.
citation: Trowbridge CA, Gower BA, Nagy TR, Hunter GR, Treuth MS, Goran MI. Maximal aerobic capacity in African-American and Caucasian prepubertal children. Am J Physiol. 1997 Oct;273(4):E809-14. doi: 10.1152/ajpendo.1997.273.4.E809.
citation: Hunter GR, Weinsier RL, McCarthy JP, Enette Larson-Meyer D, Newcomer BR. Hemoglobin, muscle oxidative capacity, and VO2max in African-American and Caucasian women. Med Sci Sports Exerc. 2001 Oct;33(10):1739-43. doi: 10.1097/00005768-200110000-00019.
citation: Steele IC, McDowell G, Moore A, Campbell NP, Shaw C, Buchanan KD, Nicholls DP. Responses of atrial natriuretic peptide and brain natriuretic peptide to exercise in patients with chronic heart failure and normal control subjects. Eur J Clin Invest. 1997 Apr;27(4):270-6. doi: 10.1046/j.1365-2362.1997.1070653.x.
citation: Shetty NS, Gaonkar M, Patel N, Vekariya N, Yerabolu K, Dhaliwal JS, Buford TW, Gower B, Li P, Wang TJ, Arora G, Arora P. Differences in natriuretic peptide response in self-identified white and black individuals: a physiological clinical trial. Nat Commun. 2025 Feb 13;16(1):1621. doi: 10.1038/s41467-024-55648-2.