Race, Natriuretic Peptides and Physiological Perturbations

NCT03070184 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB-170214001K23HL146887
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy; Pre Hypertension

Keywords

Racial differences

Outcome Measures

Primary Outcomes (3)

• Change in Plasma BNP After 6-weeks of Beta-Blocker

  Mean percentage change in plasma BNP concentrations in response to 6 weeks of Beta-Blocker between Black participants and White participants

  6 weeks

• Change in Plasma NT-proBNP After 6-weeks of Beta-Blocker

  Mean percentage change in plasma NT-proBNP concentrations in response to 6 weeks of Beta-Blocker between Black participants and White participants

  6 weeks

• Change in Plasma MR-proANP After 6-weeks of Beta-Blocker

  Mean percentage change in plasma MR-proANP concentrations in response to 6 weeks of Beta-Blocker between Black participants and White participants

  6 weeks

Secondary Outcomes (3)

• 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)

Study Arms (2)

Black Participants

EXPERIMENTAL

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.

Other: Exercise capacity VO2 max determination; Dietary Supplement: Standardized meals; Other: Exercise challenge; Drug: Metoprolol Succinate ER

White Participants

ACTIVE COMPARATOR

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.

Other: Exercise capacity VO2 max determination; Dietary Supplement: Standardized meals; Other: Exercise challenge; Drug: Metoprolol Succinate ER

Interventions

Exercise capacity VO2 max determination OTHER

Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol.

Black Participants; White Participants

Standardized meals DIETARY_SUPPLEMENT

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

Black Participants; White Participants

Exercise challenge OTHER

Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill.

Black Participants; White Participants

Metoprolol Succinate ER DRUG

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

Black Participants; White Participants

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (5)

• 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.

  PMID: 16476851 RESULT

• 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.

  PMID: 9357812 RESULT

• 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.

  PMID: 11581560 RESULT

• 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.

  PMID: 9134374 RESULT

• 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.

  PMID: 39948072 RESULT

MeSH Terms

Conditions

Prehypertension

Interventions

Metoprolol

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Results Point of Contact

• Title: Nehal Vekariya, MS - Clinical Research Coordinator III
• Organization: The University of Alabama at Birmingham

nvekariya@uabmc.edu

2059347173

Study Officials

• Pankaj Arora, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 28, 2017
• First Posted: March 3, 2017
• Study Start: April 30, 2017
• Primary Completion: December 31, 2023
• Study Completion: April 30, 2024
• Last Updated: March 12, 2025
• Results First Posted: February 27, 2025

Record last verified: 2025-03

Locations

US (1)