HealthyPhase 2NCT03070184
Race, Natriuretic Peptides and Physiological Perturbations
A Phase 2 study testing Exercise capacity VO2 max determination, Standardized meals and Exercise challenge in people with Healthy and Pre Hypertension, run by University of Alabama at Birmingham at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, Pre Hypertension
- What is being tested?
- Exercise capacity VO2 max determination, Standardized meals and Exercise challenge
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Apr 2017to 30 Apr 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: Racial Differences in the Natriuretic Peptide Response to Exercise and Beta-blockers
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.
Read the 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.
- Conditions
- Healthy, Pre Hypertension
- Being tested
- Exercise capacity VO2 max determination, Standardized meals, Exercise challenge, Metoprolol Succinate ER
- Keywords
- Racial differences
- Medical subject headings
- Prehypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise capacity VO2 max determinationOther
Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol.
Standardized mealsDietary supplement
Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB).
Exercise challengeOther
Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill.
Metoprolol Succinate ERDrug
Each participant will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day for total duration of 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Exercise capacity VO2 max determination; Dietary Supplement: Standardized meals; Other: Exercise challenge; Drug: Metoprolol Succinate ER |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 6 weeks
Secondary outcomes (3)
Change in Plasma BNP After Standardized Exercise Challenge
Mean percentage change in plasma BNP concentrations in response to exercise
Measured: 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 in response to exercise
Measured: 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 in response to exercise
Measured: Mean percentage change in plasma MR-proANP concentrations from baseline to 20 minutes post-exercise (immediately after exercise)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study start30 Apr 2017
- Primary completion31 Dec 2023
- Study completion30 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Pankaj Arora, MD, University of Alabama at Birmingham
- Investigators
- Pankaj Arora, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03070184
- Sponsor's protocol ID
- IRB-170214001
- Other IDs
- K23HL146887
- Status last verified
- Mar 2025
- First submitted
- 28 Feb 2017
- Last updated
- 12 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 16476851Trowbridge 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.
PubMed 9357812Hunter 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.
PubMed 11581560Steele 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.
PubMed 9134374Shetty 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.
PubMed 39948072
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Racial Differences in the Natriuretic Peptide Response to Exercise and Beta-blockers
- ClinicalTrials.gov ID
- NCT03070184
- Acronym / sponsor ID
- IRB-170214001
- Conditions
- Healthy, Pre Hypertension
- Keywords
- Racial differences
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 30 Apr 2017 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 30 Apr 2024 (actual)
- First posted
- 3 Mar 2017 (actual)
- Results
- Posted 27 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Black Participants | Experimental | Other: Exercise capacity VO2 max determination, Dietary Supplement: Standardized meals, Other: Exercise challenge, Drug: Metoprolol Succinate ERHealthy 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. |
| White Participants | Active comparator | Other: Exercise capacity VO2 max determination, Dietary Supplement: Standardized meals, Other: Exercise challenge, Drug: Metoprolol Succinate ERHealthy 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise capacity VO2 max determinationEach participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol. | Other | Black Participants, White Participants |
| Standardized mealsParticipants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). | Dietary supplement | Black Participants, White Participants |
| Exercise challengeEach participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill. | Other | Black Participants, White Participants |
| Metoprolol Succinate EREach participant will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day for total duration of 6 weeks. | Drug | Black Participants, White Participants |
Primary outcome
Change in Plasma BNP After 6-weeks of Beta-Blocker
Time frame: 6 weeks
Mean percentage change in plasma BNP concentrations in response to 6 weeks of Beta-Blocker between Black participants and White participants
Change in Plasma NT-proBNP After 6-weeks of Beta-Blocker
Time frame: 6 weeks
Mean percentage change in plasma NT-proBNP concentrations in response to 6 weeks of Beta-Blocker between Black participants and White participants
Change in Plasma MR-proANP After 6-weeks of Beta-Blocker
Time frame: 6 weeks
Mean percentage change in plasma MR-proANP concentrations in response to 6 weeks of Beta-Blocker between Black participants and White participants
3 secondary outcomes
Change in Plasma BNP After Standardized Exercise Challenge
Time frame: 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
Time frame: 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
Time frame: Mean percentage change in plasma MR-proANP concentrations from baseline to 20 minutes post-exercise (immediately after exercise)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 16476851Davis 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 publication: PubMed 9357812Trowbridge 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 publication: PubMed 11581560Hunter 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 publication: PubMed 9134374Steele 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 publication: PubMed 39948072Shetty 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pankaj Arora, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Exercise capacity VO2 max determination, Standardized meals and Exercise challenge in people with Healthy and Pre Hypertension, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Plasma BNP After 6-weeks of Beta-Blocker (time frame: 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03070184, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2025.