Race, Natriuretic Peptides and Physiological Perturbations

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Recruiting

CT.gov ID

NCT03070184

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Pre Hypertension	Other: Exercise capacity VO2 max determination Dietary Supplement: Standardized meals Other: Exercise challenge Drug: Metoprolol Succinate ER	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Apr 30, 2017

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: African-American 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 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.
Active Comparator: Caucasians (White) 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 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.

Arm

Intervention/Treatment

Experimental: African-American

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

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.

Active Comparator: Caucasians (White)

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

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.

Outcome Measures

Primary Outcome Measures

Change in plasma NTproBNP after 6-weeks of beta-blocker [6 weeks]
Fold change in plasma NTproBNP concentrations in response to 6 weeks of metoprolol between African-Americans and whites
Change in plasma BNP after Exercise [About 3 hours on the exercise challenge visit day after consuming study meals for 3 days]
Fold change in plasma BNP concentrations in response to exercise

Secondary Outcome Measures

Change in plasma BNP, NTproANP and MRproANP [6 weeks]
Fold change in plasma BNP, NTproANP and MRproANP concentrations in response to 6 weeks of metoprolol between African-Americans and whites

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

Principal Investigator: Pankaj Arora, MD, University of Alabama at Birmingham

Study Documents (Full-Text)

Informed Consent Form - Apr 14, 2019

More Information

Publications

None provided.

Responsible Party:

Pankaj Arora, MD, Assistant Professor, University of Alabama at Birmingham

ClinicalTrials.gov Identifier:

NCT03070184

Other Study ID Numbers:

IRB-170214001

First Posted:

Mar 3, 2017

Last Update Posted:

Nov 8, 2021

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Pankaj Arora, MD, Assistant Professor, University of Alabama at Birmingham

Racial differences

Additional relevant MeSH terms:

Prehypertension

Metoprolol

Study Results

No Results Posted as of Nov 8, 2021