Race, Natriuretic Peptides and Physiological Perturbations

Healthy Clinical Trial

Official title:

Racial Differences in the Natriuretic Peptide Response to Exercise and Beta-blockers

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03070184
• Other study ID #: IRB-170214001
• Secondary ID: K23HL146887
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 30, 2017
• Est. completion date: June 30, 2024

Study information

• Verified date: March 2024
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: June 30, 2024
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy
• Pre Hypertension
• Prehypertension

Intervention

Other:
• Exercise capacity VO2 max determination
Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol.

Dietary Supplement:
• Standardized meals
Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB).

Other:
• Exercise challenge
Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill.

Drug:
• Metoprolol Succinate ER
Each participant will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day for total duration of 6 weeks.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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.10 — View 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. — View 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 Ap — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in plasma NTproBNP after 6-weeks of beta-blocker	Fold change in plasma NTproBNP concentrations in response to 6 weeks of metoprolol between African-Americans and whites	6 weeks
Primary	Change in plasma BNP after Exercise	Fold change in plasma BNP concentrations in response to exercise	About 3 hours on the exercise challenge visit day after consuming study meals for 3 days
Secondary	Change in plasma BNP, NTproANP and MRproANP	Fold change in plasma BNP, NTproANP and MRproANP concentrations in response to 6 weeks of metoprolol between African-Americans and whites	6 weeks