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Race, Natriuretic Peptides and Physiological Perturbations

Primary Purpose

Healthy, Pre Hypertension

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Exercise capacity VO2 max determination
Standardized meals
Exercise challenge
Metoprolol Succinate ER
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Healthy focused on measuring Racial differences

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 18 to 40 years
  • Blood pressure less than 140/90 mm Hg
  • Able to perform exercise capacity test
  • BMI 18-25 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

Sites / Locations

  • University of Alabama at BirminghamRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

African-American

Caucasians (White)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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
Change in plasma BNP after Exercise
Fold change in plasma BNP concentrations in response to exercise

Secondary Outcome Measures

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

Full Information

First Posted
February 28, 2017
Last Updated
June 12, 2023
Sponsor
University of Alabama at Birmingham
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1. Study Identification

Unique Protocol Identification Number
NCT03070184
Brief Title
Race, Natriuretic Peptides and Physiological Perturbations
Official Title
Racial Differences in the Natriuretic Peptide Response to Exercise and Beta-blockers
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 30, 2017 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Pre Hypertension
Keywords
Racial differences

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
African-American
Arm Type
Experimental
Arm Description
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.
Arm Title
Caucasians (White)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Exercise capacity VO2 max determination
Intervention Description
Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol.
Intervention Type
Dietary Supplement
Intervention Name(s)
Standardized meals
Intervention Description
Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB).
Intervention Type
Other
Intervention Name(s)
Exercise challenge
Intervention Description
Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill.
Intervention Type
Drug
Intervention Name(s)
Metoprolol Succinate ER
Intervention Description
Each participant will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day for total duration of 6 weeks.
Primary Outcome Measure Information:
Title
Change in plasma NTproBNP after 6-weeks of beta-blocker
Description
Fold change in plasma NTproBNP concentrations in response to 6 weeks of metoprolol between African-Americans and whites
Time Frame
6 weeks
Title
Change in plasma BNP after Exercise
Description
Fold change in plasma BNP concentrations in response to exercise
Time Frame
About 3 hours on the exercise challenge visit day after consuming study meals for 3 days
Secondary Outcome Measure Information:
Title
Change in plasma BNP, NTproANP and MRproANP
Description
Fold change in plasma BNP, NTproANP and MRproANP concentrations in response to 6 weeks of metoprolol between African-Americans and whites
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 18 to 40 years Blood pressure less than 140/90 mm Hg Able to perform exercise capacity test BMI 18-25 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nehal Vekariya, MS
Phone
205-934-7173
Email
nvekariya@uabmc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Leigh Powell, MSN, RN
Phone
205-975-9859
Email
lcpowell@uabmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pankaj Arora, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
16476851
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.
Results Reference
result
PubMed Identifier
9357812
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.
Results Reference
result
PubMed Identifier
11581560
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.
Results Reference
result
PubMed Identifier
9134374
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.
Results Reference
result

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Race, Natriuretic Peptides and Physiological Perturbations

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