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| ID | Type | Description | Link |
|---|---|---|---|
| K23HL146887 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exercise capacity VO2 max determination | Other | Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Plasma BNP After Standardized Exercise Challenge | Mean percentage change in plasma BNP concentrations in response to exercise | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pankaj Arora, MD | University of Alabama at Birmingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16476851 | Result | 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. | |
| 9357812 | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Black Participants | 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. Exercise capacity VO2 max determination: Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol. Standardized meals: Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). Exercise challenge: Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill. 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. |
| FG001 | White Participants | 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. Exercise capacity VO2 max determination: Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol. Standardized meals: Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). Exercise challenge: Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill. 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Black Participants | 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. Exercise capacity VO2 max determination: Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol. Standardized meals: Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). Exercise challenge: Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill. 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Posted | Mean | 95% Confidence Interval | Percentage Change in Plasma BNP levels | 6 weeks |
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Adverse events were collected after the completion of the screening visit, during the exercise visits, and during the Beta-Blocker intervention period for a total of 14 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Black Participants | 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. Exercise capacity VO2 max determination: Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol. Standardized meals: Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). Exercise challenge: Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill. 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nehal Vekariya, MS - Clinical Research Coordinator III | The University of Alabama at Birmingham | 2059347173 | nvekariya@uabmc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 18, 2023 | Feb 5, 2025 | Prot_SAP_005.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 18, 2023 | Jul 8, 2024 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D058246 | Prehypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D008790 | Metoprolol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| 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). |
|
| Exercise challenge | Other | Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill. |
|
| 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. |
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Mean percentage change in plasma NT-proBNP concentrations in response to exercise |
| 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 | Mean percentage change in plasma MR-proANP concentrations from baseline to 20 minutes post-exercise (immediately after exercise) |
| 11581560 | 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. |
| 9134374 | 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. |
| 39948072 | 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. |
| BG001 | White Participants | 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. Exercise capacity VO2 max determination: Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol. Standardized meals: Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). Exercise challenge: Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill. 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. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Body Mass Index (BMI) | Median | Inter-Quartile Range | kg/m² |
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| Systolic Blood Pressure (SBP) | Median | Inter-Quartile Range | mmHg |
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| Diastolic Blood Pressure (DBP) | Median | Inter-Quartile Range | mmHg |
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| Heart Rate | Median | Inter-Quartile Range | beats per minute |
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| Fasting Glucose | Median | Inter-Quartile Range | mg/dL |
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| Hemoglobin | Median | Inter-Quartile Range | g/dL |
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| Insulin | Median | Inter-Quartile Range | mg/dL |
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| Creatinine | Median | Inter-Quartile Range | mg/dL |
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| Aspartate Aminotransferase (AST) | Median | Inter-Quartile Range | U/L |
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| Alanine Aminotransferase (ALT) | Median | Inter-Quartile Range | U/L |
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| Midregional pro- Atrial Natriuretic Peptide (MRproANP) | Median | Inter-Quartile Range | pmol/L |
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| B-type Natriuretic Peptide (BNP) | Median | Inter-Quartile Range | ng/L |
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| N-terminal pro-Btype Natriuretic Peptide (NTproBNP) | Median | Inter-Quartile Range | ng/L |
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| Left Ventricular Hypertrophy | Left Ventricular Hypertrophy (LVH) was assessed using the Minnesota coding criteria for high amplitude R waves. Criteria include: (1) R amplitude > 26 mm in leads V5 or V6, or > 20 mm in leads I, II, III, aVF; or R amplitude > 12 mm in lead aVL; (2) Right R amplitude ≥ 5 mm and R ≥ S amplitude in the majority of beats in lead V1, with R amplitude located to the left of V1; or (3) R amplitude > 15 mm but ≤ 20 mm in lead I, or R amplitude in leads V5 or V6 plus S amplitude in lead V1 > 35 mm. All amplitudes were measured from the second-to-last complete normal beat. | Cardiac function parameters where only collected for a limited number of participants | Number | Percentage of Participants |
|
| Left Atrial Enlargement | Left Atrial Enlargement (LAE) was assessed using electrocardiographic (ECG) criteria. Criteria include: (1) In lead II: presence of a bifid P wave with > 40 ms between the two peaks or a total P wave duration > 110 ms; (2) In lead V1: presence of a biphasic P wave with a terminal negative portion lasting > 40 ms, or a terminal negative portion > 1 mm in depth. These criteria were used to identify LAE based on ECG analysis. | Cardiac function parameters where only collected for a limited number of participants | Number | Percentage of Participants |
|
| OG001 | White Participants | 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. Exercise capacity VO2 max determination: Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol. Standardized meals: Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). Exercise challenge: Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill. 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. |
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| Primary | 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 | Posted | Mean | 95% Confidence Interval | Percentage Change in Plasma NT-proBNP | 6 weeks |
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| Primary | 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 | Posted | Mean | 95% Confidence Interval | Percentage Change in Plasma MR-proANP | 6 weeks |
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| Secondary | Change in Plasma BNP After Standardized Exercise Challenge | Mean percentage change in plasma BNP concentrations in response to exercise | Posted | Mean | 95% Confidence Interval | Percentage change in Plasma BNP | Mean percentage change in plasma BNP concentrations from baseline to 20 minutes post-exercise (immediately after exercise) |
|
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| Secondary | Change in Plasma NT-proBNP After Standardized Exercise Challenge | Mean percentage change in plasma NT-proBNP concentrations in response to exercise | Posted | Mean | 95% Confidence Interval | Percentage change in Plasma NT-proBNP | Mean percentage change in plasma NT-proBNP concentrations from baseline to 20 minutes post-exercise (immediately after exercise) |
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| Secondary | Change in Plasma MR-proANP After Standardized Exercise Challenge | Mean percentage change in plasma MR-proANP concentrations in response to exercise | Posted | Mean | 95% Confidence Interval | Percentage change in Plasma MR-proANP | Mean percentage change in plasma MR-proANP concentrations from baseline to 20 minutes post-exercise (immediately after exercise) |
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|
| 0 |
| 40 |
| 0 |
| 40 |
| 6 |
| 40 |
| EG001 | White Participants | 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. Exercise capacity VO2 max determination: Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol. Standardized meals: Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). Exercise challenge: Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill. 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. | 0 | 40 | 0 | 40 | 7 | 40 |
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Vasovagal Response | Nervous system disorders | Non-systematic Assessment |
|
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| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| Unknown or Not Reported |
|