ClinicalTrials.gov
ClinicalTrials.gov Menu

Race, Natriuretic Peptides and Physiological Perturbations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03070184
Recruitment Status : Recruiting
First Posted : March 3, 2017
Last Update Posted : May 16, 2018
Sponsor:
Information provided by (Responsible Party):
Pankaj Arora, MD, University of Alabama at Birmingham

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 1

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Racial Differences in the Natriuretic Peptide Response to Exercise and Beta-blockers
Actual Study Start Date : April 30, 2017
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Metoprolol

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.




Primary Outcome Measures :
  1. Change in plasma NTproANP [ Time Frame: 6 weeks ]
    Fold change in plasma NTproANP concentrations in response to 6 weeks of metoprolol between African-Americans and whites


Secondary Outcome Measures :
  1. Change in plasma NTproANP [ Time Frame: About 3 hours on the exercise challenge visit day after consuming study meals for 3 days ]
    Fold change in plasma NTproANP concentrations in response to exercise challenge between African-Americans and whites

  2. Change in plasma NTproBNP [ Time Frame: 6 weeks ]
    Fold change in plasma NTproBNP concentrations in response to 6 weeks of metoprolol between African-Americans and whites

  3. Change in plasma NTproBNP [ Time Frame: About 3 hours on the exercise challenge visit day after consuming study meals for 3 days ]
    Fold change in plasma NTproANP concentrations in response to exercise challenge between African-Americans and whites



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03070184


Contacts
Contact: Nirav Patel, MD 205-934-6058 npatel@uabmc.edu
Contact: Mehak Goel, PhD 205-975-4021 mehakgoel@uabmc.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Pankaj Arora, MD University of Alabama at Birmingham

Publications of Results:
Responsible Party: Pankaj Arora, MD, Assistant Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT03070184     History of Changes
Other Study ID Numbers: IRB-170214001
First Posted: March 3, 2017    Key Record Dates
Last Update Posted: May 16, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pankaj Arora, MD, University of Alabama at Birmingham:
Racial differences

Additional relevant MeSH terms:
Prehypertension
Vascular Diseases
Cardiovascular Diseases
Metoprolol
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action