Clinical trial NCT03070184
Conditions: Healthy Pre Hypertension
Keywords: Racial differences
Sponsor: University of Alabama at Birmingham
Start date: 2017-04-30; Completion date: 2024-04-30
Enrollment: 80 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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 2: 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.
Interventions: intervention 1: Exercise capacity VO2 max determination intervention 2: Standardized meals intervention 3: Exercise challenge intervention 4: Metoprolol Succinate ER
Intervention descriptions: intervention 1: Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol. intervention 2: Participants will consume the standardized study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). intervention 3: Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill. intervention 4: Each participant will receive metoprolol succinate starting at 50mg/day, titrated bi-weekly up to 200 mg/day for total duration of 6 weeks.

Protocol documents:
Prot_SAP_005.pdf: 
UAB IRB  
Approved 
18-Jan-2023 
 
Study Title: Race, Natriuretic Peptides and Physiological Perturbations 
NCT number: NCT03070184 
UAB IRB Protocol number: IRB-170214001 
Investigator: Dr. Pankaj Arora, MD, FAHA 
 
Study Design 
This was an investigator-initiated single-center clinical trial conducted at the University of 
Alabama at Birmingham. All participants provided written informed consent. The study was 
approved by the University of Alabama at Birmingham Institutional Review Board. The detailed 
study protocol is included in this document. This study was registered on ClinicalTrials.gov as 
NCT03070184. 
 
Rationale and Hypothesis 
There are significant racial disparities in the burden of cardiovascular disease, with hypertension 
and heart failure being more prevalent in Black individuals than in White individuals. We have 
observed lower resting levels of NPs in Black individuals, raising the possibility of impaired NP 
production. Little is known about whether these race-related differences extend to dynamic 
changes in NP levels. Beta-blockers are commonly used drugs in hypertension, especially in 
individuals with co-existing coronary artery disease. They are also a cornerstone of standard 
heart failure therapy. Beta-blockers have been shown to be associated with a short-term increase 
in NPs. Hence, we hypothesize that Black individuals will have reduced release of NPs after 6 
weeks of metoprolol compared with White individuals. 
Similarly, exercise has been shown to increase the plasma concentration of NPs immediately 
after peak exercise in multiple previous human studies of healthy volunteers.73,80,81,97 Although 
the mechanism is incompletely understood, it is thought that exercise causes degranulation of 
secretory granules located within the heart.75,98 The amount of NPs stored within the secretory 
granules is known to rise in parallel to the resting concentrations of NPs.99-102 As mentioned 
above, NP values have been shown to be lower in Black individuals compared with their White 
counterparts. Therefore, Black individuals may have a lower NP response to exercise compared 
with White individuals. 
 
Specific Aims 
The proposed single-center clinical trial will compare the response of the NP system to 
metoprolol and exercise among healthy, young Black and White individuals. 
Primary Aim 
To compare the NP (NT-proBNP, BNP, and MR-proANP) response with metoprolol 
therapy at 6 weeks in Black and White individuals. 


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Secondary Aim 
To compare the NP (NT-proBNP, BNP, and MR-proANP) response immediately after 
standardized exercise in Black and White individuals. 
 
Participant Selection 
Inclusion Criteria: 
1. Self-identified Black or White adults 
2. Age between 18 and 40 years 
3. Body mass index between 18 to 30 kg/m2 
4. No history of hypertension (seated blood pressure <140/90 mm Hg and not taking 
antihypertensive medications) 
5. Willing to take the study medication 
6. Able to exercise 
Exclusion Criteria: 
1. Decreased renal function (estimated glomerular filtration rate <60 mL/min/1.73m2) 
2. Systolic blood pressure <100 mm Hg, diastolic blood pressure <60 mm Hg, or heart 
rate <60/min at screening 
3. Use of antihypertensive medications 
4. History of cardiovascular disease 
5. History of diabetes or use of antidiabetic medications 
6. Anemia (hematocrit <41% in males and <35% in females) 
7. Pregnancy (using urine pregnancy test) 
8. Hormone replacement therapy/oral contraceptive use 
9. Elevated liver function tests (>3x upper normal limit) 
10. Depression 
11. History of smoking or current smoking 
 
Recruitment 
The proposed single-center clinical trial will be conducted at the University of Alabama at 
Birmingham (UAB). UAB is located in Birmingham, AL (metropolitan population ~ 1.2 
million: 29% African-American, 56% white), making this an ideal environment in which to 
conduct studies that include African-American and white individuals. Several recruitment 
approaches will be used: 1) advertisements will be posted in local newspapers and online to 
recruit healthy subjects from the greater Birmingham area; 2) announcements regarding the study 
will be made on radio stations that have high market penetration in African-American 
communities to enhance recruitment; and 3) outreach through the UAB CCTS Community 
Engagement Research Core. 
 
Study Procedures 
A participating subject’s study period will span ~13-16 weeks from the screening visit to study 
completion. The timeline and study procedures are shown in Table 1. 


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Table 1. Study Flowchart and Timeline 
 
Days 
Days from 
Previous Visit 
Visit 
Location 
Time (hours) 
Procedures 
 
-10 to -8 
0 
Pre-Screening 
Home 
0.5 
-Discuss study objectives, 
inclusion/exclusion criteria, timeline, 
procedures & possible side effects 
- Telephonic pre-screening 
 
 
 
-7 
0 
Screening Visit (Visit 1) 
CRU 
1 
-Written consent 
-History & physical exam 
-Vitals check 
-Screening Labs 
-Urine Pregnancy Test (if applicable) 
-Dietician meeting (to review the 
standardized meals and for meal 
instructions) 
-6 
2 
Exercise Capacity 
Determination Visit (Visit 
2) + 3 days Meal pick up 
UCEM 
2 
-Vitals Check 
-VO2 max test 
- 3 days meal pick up from CRU 
The participants will consume 3 days of standardized meals prior to visit 3 
-3 
4 
Exercise Challenge 
Test(Visit 3) 
UCEM 
3 
-24-hour urine collection prior to the 
visit 
-Vitals check 
-Blood draw & spot urine collection 
-Exercise Challenge test 
0 
1 
Drug Initiation Visit 
(Visit 4) 
CRU 
1 
-24-hour urine collection prior to the 
visit 
-History & physical exam 
-Vitals check and EKG 
-Blood draw 
-Urine Pregnancy Test (if applicable) 
-Adherence & adverse events tracking 
-Provide the participant with 1 pre- 
labeled bottle (15 tablets per bottle) of 
metoprolol succinate XL 50 mg - 
Provide the participant with the 
medication log 
7 
7 
Phone Interview I 
Home 
0.25 
-Adherence & adverse events tracking 
14 
7 
Interim Visit 1 (Visit 5) 
CRU 
1 
-24-hour urine collection prior to the 
visit 
-History & physical exam 
-Vitals check and EKG 
-Blood draw 
-Urine Pregnancy Test (if applicable) 


UAB IRB  
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- Adherence & adverse events tracking 
- Provide the participant with 1 pre- 
labeled bottle (15 tablet per bottle) of 
metoprolol succinate XL 100mg 
-Provide the participant with the 
medication log 
-Pill 
count and drug log check 
21 
7 
Phone Interview II 
Home 
0.25 
-Adherence & adverse events tracking 
28 
7 
Interim Visit 2 (Visit 6) 
CRU 
1 
24-hour urine collection prior to the visit 
-History & physical exam 
-Vitals check and EKG 
-Blood draw 
-Urine Pregnancy Test (if applicable) 
-Adherence & adverse events tracking 
-Provide the participant with 1 pre- 
labeled bottle (15 tablets per bottle) of 
metoprolol succinate XL 200mg 
-Provide the participant with the 
medication log 
-Pill 
count and drug log check 
35 
7 
Phone Interview III 
Home 
0.25 
-Adherence & adverse events tracking 
42 
7 
Final visit (Visit 7) 
CRU 
1 
-History & Physical 
-Vitals check and EKG 
-Blood Draw 
-Urine Pregnancy Test (if applicable) 
-Pill count and drug log check 
49 
7 
Follow-up visit (Visit 8) 
CRU 
1 
-Vitals check 
End of Study 
Abbreviation: CRU, Clinical Research Unit; UCEM: UAB Center for Exercise Medicine 
 
Visit # 1 (Screening Visit):  
During the screening visit, the study investigator(s) will obtain consent from the study subjects. 
After obtaining the consent of the study subjects, personal and medical history will be taken. 
Physical examination, including vitals (like blood pressure and heart rate), will be performed by 
the study investigator(s). A urine pregnancy test will be administered to the female subjects to 
confirm their pregnancy status. In addition to these, 25cc (5 teaspoons) of blood will be drawn 
for screening labs, including baseline metabolic profile, complete blood count, and liver function 
tests. Furthermore, the dietician will explain the 3 days of a standardized diet. If the subject 
agrees to adhere to the study diet, follow the study protocol, and meet the inclusion criteria, then 
they will be enrolled in the study. 
 
Visit # 2 (Baseline visit-Meal Pick-up):  


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Subjects will come for a baseline visit (scheduled according to subjects’ convenience) to 
the UCEM for determination of maximal oxygen capacity (VO2 max). Subjects will be asked to 
fast overnight (>6 hours) prior to this visit and not to drink caffeine and alcoholic beverages 24 
hours prior to this visit. 
 
• A maximal modified Bruce treadmill protocol will be used to determine aerobic fitness/VO2 
max. Monitoring will consist of a 12-lead electrocardiogram and BP measurements will be taken 
every two minutes. 
• Oxygen uptake and carbon dioxide production will be measured continuously using a TrueOne 
2400 metabolic cart. 
• Achievement of maximal oxygen uptake (VO2 max) was ascertained by the exercise 
physiologist based on standard criteria for heart rate (HR within 10 beats/min of estimated 
maximum), respiratory exchange ratio (RER >1.2), and plateauing of VO2/min/kg. 
• After determining the VO2 max, subjects will pick up 3 days of standardized diet from the 
metabolic kitchen of CRU. Meals will be provided to subjects at no cost. The daily standardized 
diet will be composed of 51% carbohydrate, 31% fats, 18% proteins, ~4.5 gm sodium, and ~2.5 
gm potassium. All meals will be prepared in the CRU metabolic kitchen. A menu and food 
records form included in the packet. 
• A container for 24-hour urine collection will be provided. Instruction for the collection of 24- 
hour urine will be provided by the study coordinator. 
 
Prior to 3rd/Exercise Challenge visit: 
Three days prior to 3rd visit, subjects will consume the meals that were provided by the CRU. 
Subjects will be asked to collect 24-hour urine and fast overnight (>6 hours) prior 
to 3rd visit. Subjects will be asked not to drink caffeine and alcoholic beverages 24 hours prior to 
this visit. Before coming for 3rd visit, subjects will drop off their 24-hour urine sample at the 
Outreach Lab. 
 
Visit # 3/ Exercise Challenge visit:  
• Subjects will come to the PAC and rest for 1 hour in supine position. Medical history and vital 
sign measurements (blood pressure and heart rate) will be collected. After 1 hour of rest, 20cc of 
blood or 4 teaspoons will be drawn by a nurse for the assays. Blood samples will be tested for 
natriuretic peptide levels, insulin, and glucose. 
• Afterward, subjects will be asked to perform the exercise challenge test. The exercise challenge 
is designed to give each subject comparable amounts of physiological stress. Each subject will 
walk at 70% of his/her VO2 max for 20 minutes. 
• The exercise challenge has a 4-minute warmup starting with 3 mph at zero grade for two 
minutes, progressing to 3 mph at a 3% grade for 1 minute, followed by 3 mph at a 6% grade for 
one minute. 


UAB IRB  
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• Using the American College of Sports Medicine metabolic equations, treadmill grade and speed 
will be adjusted to attain 70% VO2 max. Each subject will walk at 70 % of their VO2 max for 
20 minutes. At the end of the exercise challenge, participants will undergo a 4-minute cool- 
down by walking at 2 mph at 0 grade. 
• Subjects will be asked to take a rest for 30 minutes. Before, immediately, 15 minutes, and 30 
minutes after the exercise challenge, blood samples will be collected to measure NP levels. 
Participants were asked to provide urine samples to measure urinary sodium levels at the start 
and 30 minutes after the end of the exercise challenge. 
• During the exercise challenge visit, subjects will be asked not to drink water. Subjects can drink 
water after completing the exercise challenge. 
• A container for 24-hour urine collection will be provided. Instruction for the collection of 24- 
hour urine will be provided by the study coordinator. 
 
Visit # 4/ Drug initiation visit:  
• Three to seven days after 3rd visit, subjects will come for 4th visit. 
• Subjects will be asked to fast overnight (>6 hours) prior to this visit and not to drink caffeine and 
alcoholic beverages 24 hours prior to this visit. 
• Before coming for the 4th visit, subjects will drop off 24-hour urine samples at the outreach 
lab. A urine sample will be tested for sodium, protein, and creatinine levels. 
• Subjects will come to the CRU and will be asked to take a rest for 1 hour. 
• If a female is in the reproductive age group, a urine pregnancy test will be performed to rule out 
pregnancy. BP and heart rate (HR) will be measured and venous blood will be drawn. 
• If the systolic blood pressure is >100 mmHg, diastolic blood pressure is >50 mm Hg, and heart 
rate is >60 bpm, then a two-week supply of 50 mg of metoprolol succinate will be provided. The 
local Investigational Drug Services will dispense pre-labeled bottles (15 tablets per bottle) of 
metoprolol succinate XL 50 mg in bulk (6 bottles for each dose). A study physician/study 
coordinator will obtain these pre-labeled bottles from the research pharmacy. Drug bottles will 
be kept in locked cabinets. A study physician will dispense each bottle to the study subjects 
according to the study visits. A total of 15 capsules will be dispensed at this time, which 
provides sufficient supply for 2 weeks plus 1 additional pill in the event that the visit cannot be 
scheduled exactly 2 weeks to reach the interim visit 1 (Visit #5). Subjects will be instructed to 
take one capsule once a day. 
• Subjects will be called by the study doctor to assess medicine side effects within 7 days after this 
visit. 
• Drug compliance and side effects will be assessed through a telephone call after 7 days of visit 
and a medication log. 
 
Visit # 5/Interim visit 1:  
• 
Two weeks after visit #4, subjects will come for this visit 


UAB IRB  
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• 
Subjects will be asked to fast overnight (>6 hours) prior to this visit and not to drink caffeine and 
alcoholic beverages 24 hours prior to this visit. 
• 
Subjects will come to the CRU and will be asked to take a rest for 1 hour. 
• 
Blood pressure and heart rate will be measured and venous blood will be drawn after 1 hour of 
rest. Blood samples will be tested for natriuretic peptide levels, insulin, and glucose. 
• 
Compliance will be assessed by doing a pill count and reviewing the medication log. 
• 
Subjects will be asked about any possible side effects from the metoprolol use in the previous 2 
weeks. 
• If compliant and have no side effects, subjects will be given a 2-week supply of 100 mg/day of 
metoprolol succinate. The local Investigational Drug Services will dispense pre-labeled bottles 
(15 tablets per bottle) of metoprolol succinate XL 100 mg in bulk (6 bottles for each dose). A 
study physician/study coordinator will obtain these pre-labeled bottles from the research 
pharmacy. Drug bottles will be kept in locked cabinets. A study physician will dispense each 
bottle to the study subjects according to the study visits. A total of 15 capsules will be dispensed 
at this time, which provides sufficient supply for 2 weeks plus 1 additional pill in the event that 
the visit cannot be scheduled exactly 2 weeks to reach the interim visit 2 (Visit 6). Subjects will 
be instructed to take one capsule once a day. 
• Subjects will be called by the study doctor to assess medicine side effects within 7 days after this 
visit. 
• Drug compliance and side effects will be assessed through a telephone call after 7 days of visit 
and a medication log. 
 
Visit # 6/Interim Visit 2:  
• Two weeks after visit #5, subjects will come for this visit. The same protocol as that for visit 
# 5 will be followed. Compliance will be assessed and if no side effects are reported, subjects 
will be given a 2-week supply of 200 mg/day of Metoprolol succinate. The local Investigational 
Drug Services will dispense pre-labeled bottles (15 tablets per bottle) of metoprolol succinate XL 
200 mg in bulk (6 bottles for each dose). A study physician/study coordinator will obtain these 
pre-labeled bottles from the research pharmacy. Drug bottles will be kept in locked cabinets. A 
total of 15 capsules will be dispensed at this time, which provides sufficient supply for 2 weeks 
plus 1 additional pill in the event that the visit cannot be scheduled exactly 2 weeks to reach the 
final visit (Visit 7). Subjects will be instructed to take one capsule once a day. 
• Subjects will be called by the study doctor to assess medicine side effects within 7 days after this 
visit. 
• Drug compliance and side effects will be assessed through a telephone call after 7 days of visit 
and a medication log. 
A container for 24-hour urine collection will be provided. 
 
Visit # 7/Final Visit: 


UAB IRB  
Approved 
18-Jan-2023 
 
Two weeks after visit #6, subjects will come for this visit. On this visit, subjects will drop off 
24-hour urine collection at the outreach lab. The urine sample will be tested for sodium, protein, 
and creatinine levels. The same protocol as that for visit # 5 will be followed. Blood will 
be drawn. Blood samples will be tested for natriuretic peptide levels, insulin, and glucose.  At 
the end of this visit, the subject’s participation will be complete. 
 
Visit # 8/Follow-up Visit: 
One week after visit #7, subjects will come to the CRU for their follow-up visit. After 15 min of 
rest, blood pressure and heart rate (three times) will be measured to evaluate subjects’ well- 
being. 
 
Early Termination/Discontinuation Visit: 
At every visit, blood pressure and heart rate will be measured. Metoprolol will be discontinued 
for any systolic BP< 80 mm Hg and HR < 40 beats/minute at any visit. If the subject develops 
intolerance or any side effects from increasing the dose of metoprolol, they will go back to the 
maximally tolerated last dose to finish the 6-week duration. 
 


UAB IRB  
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Study Outcomes 
The primary endpoint in this study is the change in the NP levels, including NT-proBNP, BNP, 
and MR-proANP, in response to 6 weeks of metoprolol between young, healthy Black and White 
individuals. As the assessment of each NP is not independent of each other, we did not use the 
statistical correction of multiple testing. 
The secondary outcome of this study was the change in the NP levels, including NT-proBNP, 
BNP, and MR-proANP, in response to a standardized exercise challenge between young, healthy 
Black and White individuals. 


UAB IRB  
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Statistical Analysis 
All analyses will be conducted using SAS 9.4 (Cary, NC) and the latest version of R Statistical 
Software (R core team 2020). Participants’ demographic and baseline clinic characteristics will 
be summarized with mean and standard deviations (SD) for continuous variables and frequency 
and proportion for categorical variables. The 95% confidence interval (95%CI) will also be 
provided where appropriate. Statistical plots (scatters, histograms, Q-Q, bar charts, etc.) will be 
used to examine the distribution of data. Extreme values will be identified for validation or 
correction. The baseline differences between groups will be compared using a two-sample t-test 
for continuous variables or a Chi-square test for categorical variables. A nonparametric Wilcoxon 
test will be applied for skewed continuous data. For the primary and secondary outcomes, we will 
conduct a complete case analysis. The analysis will be conducted in individuals who completed 
both phases of the study i.e., exercise and medication. A sensitivity analysis will be conducted, 
including participants who completed a single phase (medication or exercise) of the study. All the 
tests will be two-sided with a significance level of 0.05. 
Multivariable linear mixed models using change in log-transformed NP levels as the dependent 
variable and race as the independent variable (white will be chosen as reference) will be employed. 
Participants were taken as random effects. The fixed effects included race, time, a multiplicative 
interaction term of time and race, age, sex, body mass index, and insulin levels. Percentage 
difference and 95% confidence intervals in plasma NP levels after 6 weeks of metoprolol by race 
was calculated: ([eβ–1]×100 multiplied by 6 weeks [where β is the beta coefficient from linear 
regression]). 
Power Analysis 
In the proposed study, we aim to recruit 40 Black individuals and 40 White individuals. Figure 
presents the power estimates for the detectable mean fold-change in log NT-proANP levels 
between groups (Black vs. White) from pre to post-6 weeks of metoprolol at a two-sided p-value 
of 0.05. In a prior study evaluating NP response after 6 weeks of metoprolol (similar dose and 
protocol), the mean ± SD relative change (measured in log units) in NT-proANP levels was 0.66 
± 0.45. Based on preliminary data from 5 subjects who have already completed the proposed 
study, we have measured NPs and found a 110% increase in NT-proBNP levels after 6 weeks of 
metoprolol. As shown, we have excellent power to detect relatively small-medium differences 
(28%) between Black individuals and White individuals pre and post-metoprolol. Even if we 
reduce the sample size by 20% (32 in each group) due to loss to follow-up or withdrawal, the 
detectable difference changes minimally, from 28% to 32%. 


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For the secondary outcome, we anticipate 80% power to detect a 39% (medium effect size) 
difference between groups (Black vs. White) in mean fold-change in BNP from before and after 
exercise challenge using the two-sided P value of 0.05. This is based upon data from Barletta et 
al. in which the mean ± SD relative change (measured in log units) in BNP between pre and post- 
exercise in white individuals was 0.42 ± 0.61.79 
 
 
Potential Risks 
General. Risks related to overnight fasting include hypovolemia. Subjects will be instructed to 
drink plenty of fluids the day before the visit, and will have baseline blood pressure measured 
upon arrival at the clinical research unit (CRU). Risks related to venous blood draw include 
hematoma formation and phlebitis. This is a routine procedure that is considered standard of 
care in clinical medicine. At each visit, subjects will undergo a single venous blood draw with 
removal of approximately 4 teaspoons (20 ml) of blood. All blood draws will be performed by 
trained personnel using universal precautions to protect both the subject and personnel. The 
risks to subjects are minimal, but may include pain, allergic reaction, infection, or bleeding at the 
needle stick site. These usually resolve without any specific medical therapy over the course of 
minutes to days. 
Tolerability and safety of study drug (Metoprolol). Common side effects reported in 3% or 
more cases of metoprolol use in the literature include dizziness, fatigue, and depression, 
shortness of breath, pruritus and diarrhea. Less frequent but serious side effects include 
wheezing, bronchospasm, bradyarrythmia and heart failure. However, since we are enrolling 


UAB IRB  
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healthy volunteers the frequency of any side effects is less than 1%. All subjects will be 
monitored for adverse effects and during the study visits a physician will be present to monitor 
the safety of the subject through the protocol and between study visits, a physician will be 
available 24 hours a day by phone and/or pager to subjects. Metoprolol will be discontinued for 
any systolic blood pressure< 80 mm Hg and heart rate < 50 beats/minute at any visit. If the 
subject develops intolerance or any side effects from increasing the dose of metoprolol, they will 
go back to the maximally tolerated last dose to finish the 6-week duration. 
Tolerability and safety of determination of VO2 max and performing exercise challenge. The 
risks associated with the proposed study are minimal since moderate amounts of exercise 
generally promote good health, not endanger. Our eligibility criteria are established to exclude 
individuals for whom exercise is not appropriate. However, there is still moderate to high 
likelihood of fatigue, muscle soreness, or shortness of breath during and/or after performance of 
VO2 max. There is an extremely low likelihood of injury to muscle, joint, ligaments, tendons or 
bone, tripping or falling, feeling faint or dizzy, chest pain, arrhythmia, and inconvenience. 
Furthermore, there is a very rare risk of cardiac ischemia or arrest during the peak VO2 test or 
exercise challenge. 
Tolerability and safety of standardized diets. While there is theoretic risk of eliciting 
hypertensive or hypotensive responses with standardized diets, Dr. Arora and the study team 
have decades of experience giving diets and have demonstrated that the standardized diets are 
well tolerated and safe. 
Device complications. Not applicable 
Psychosocial risks. We do not anticipate psychosocial risks to the subjects from participation in 
the proposed protocol. Strict confidentiality will be maintained to the fullest extent by the 
research team, including keeping all data in a secure, locked cabinet with limited access. All 
specimens and files will be coded after they are obtained and the code key kept in a locked 
cabinet. 
Radiation risks. No additional radiation exposure will be required by the protocol. 
Financial and legal risks. Those are felt to be minimal given the lack of expected clinical 
information relevant to employment, insurability or paternity. 
Private health information. This information will be collected during the course of the study. 
However, only key study personnel will have access to this information, which will be stored in a 
HIPAA compliant, password protected REDCap database. No protected health information will 
be shared with employers, insurers, or non-research personnel. 
 
Protection Against Risk 
Bodily fluids and biohazards. As phlebotomy for venous blood samples and urine collections 
will be performed, standard universal precautions will be utilized to protect both subjects and 
members of the research team. If discomfort, swelling, infection, or bleeding occurs in relation 
to the venous blood draw, appropriate medical therapy will be provided under the direction of the 
supervising physician. Most symptoms or side effects related to venous blood draw are 
temporary, self-resolving, and do not require any specific medical therapy. 


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Data Protection and prompt reporting of adverse events. The University of Alabama at 
Birmingham regularly reviews its policies and procedures regarding the confidentiality of study 
subjects. All staff receive training on the critical importance of maintaining confidentiality. 
Data are stored and analyzed according to subject identification numbers, and in no instances are 
subjects’ names or other identifying information available in publicly accessible files or in 
published material. Every effort is made to keep such data from being accessed inappropriately, 
but this possibility always remains, however remote. UAB Hospital has 24-hour security to 
protect all participants’ data. 
Location. The study protocol will be conducted in the UCEM and the UAB CRU (within the 
hospital with all available emergency medical personnel) under the direct supervision of a study 
physician. Portable defibrillators are present, and all staff members are certified for their use and 
CPR. Appropriate reporting, as described below, will be done in the event of an adverse event. 
Informed consent forms, case report forms, and data will be reviewed by the principal 
investigator and an independent data and safety monitor (details below) following enrollment of 
every 10 patients to ensure completeness, accuracy, and adherence to the protocol. Data to be 
reviewed includes appropriate handling and processing of blood samples and maintenance of 
patient confidentiality throughout the study. Specifically, for the interventional study, serious 
adverse events will be reported by phone, fax or e-mail within 24 hours to the UAB Human 
Research Committee, followed by a full written report within 10 working days/14 calendar days. 
Mild or moderate adverse events will be presented in progress reports at continuing reviews. 
 
Potential for Benefit to Subjects and Others 
It is not anticipated that the participants of the study will directly benefit from the proposed 
research. However, the potential benefit to society is great. As hypertension and heart failure 
are common, particularly among Black individuals, the results of the proposed studies may 
provide important knowledge regarding the biological mechanisms and inform novel preventive 
and therapeutic strategies to be tested in future trials. 
 
Monitoring and Quality Assurance 
The risks associated with the study assessments are minimal. However, we will institute a three- 
member Data and Safety Monitoring Board (DSMB), comprised of experts in cardiology (Dr. 
David A. Calhoun, MD), biostatistics (Charity J. Morgan, Ph.D.), and pulmonary medicine (Dr. 
Surya P. Bhatt, MD), who will be charged with reviewing data and safety throughout the study, 
in addition to the Principal Investigator. Informed consent, case report forms and data will be 
reviewed by the principal investigator and DSMB. The DSMB will meet at least twice a year, 
either by phone or in person, to ensure the safety of study participants. The DSMB will be 
provided access to blinded safety data, including adverse events (AEs) by frequency and by body 
system, and study withdrawals following enrollment of every 10 patients to ensure completeness, 
accuracy, and adherence to the protocol. Other data to be reviewed include appropriate handling 
and processing of blood samples, laboratory data, and maintenance of patient confidentiality. 
Safety monitoring will be performed throughout the course of the study. During and between all 
study visits and procedures, Dr. Arora will be available to address subject-related medical 
questions and ensure subject safety. At every subject visit, a study physician will carefully 


UAB IRB  
Approved 
18-Jan-2023 
 
screen for any side effects from the study drug, record vital signs and monitor compliance. Any 
study-related injuries will be promptly addressed and treated using resources available at UAB. 
All data will be recorded and stored in password-protected REDCap databases that can only be 
accessed by key study personnel. Data integrity and quality will be checked at the time of 
acquisition and entry. Prior to analyses, queries regarding missing data or extreme values will be 
addressed by checking against case report forms. Data handling and analytic methods will be 
recorded to ensure reproducibility of results. Results, when reported in any form, will be 
summarized without any patient identification. Standards for Personal Health Information will 
be followed to assure confidentiality. 
Adverse Events (AE). The investigator or study physician will be responsible for detecting, 
documenting and reporting events that meet the definition of an AE. All Serious AEs (SAEs) 
and others will be collected from the time of the first dose of metoprolol through the final study 
visit. All-cause mortality and SAEs will be reported to the DSMB, and the local regulatory 
authority within 24 hours by the study monitor (principal investigator and/or study physician at 
UAB). 
Definition of an AE. Any untoward or unfavorable medical occurrence in a participant, including 
any abnormal sign (for example, abnormal physical exam), symptom, or disease, temporally 
associated with the use of metoprolol, whether or not considered related to the participant’s 
participation in the research. Three types of adverse event data will be reported: “All-Cause 
Mortality”, “Serious”, and “Other (Not Including Serious)” Adverse Events. 
 
All-Cause Mortality 
The occurrence of death due to any unrelated cause during the 
course of the study. 
Serious Adverse Events 
(SAEs) 
Bronchospasm (1%) 
Other (Not Including 
Serious) Adverse Events 
Cardiovascular: Bradycardia (3%), Hypotension (1%), Cold 
extremities (1%) 
Dermatologic: Pruritus (5%), Rash (5%) 
Gastrointestinal: Constipation (1%), Diarrhea (5%), and 
Indigestion (1%) 
Neurologic: Dizziness (10%), Fatigue (10%), Headache 
Psychiatric: Depression (5%) 
Respiratory: Dyspnea (3%), Wheezing (1%) 
 
Events meeting the definition of an AE include. New conditions detected or diagnosed after 
metoprolol administration, even though they may have been present prior to the start of the 
study. Signs, symptoms, or the clinical sequelae of a suspected interaction. Signs, symptoms, or 
the clinical sequelae of a suspected overdose of either metoprolol or concomitant medication 
(overdose per se will not be reported as SAEs and others). 
Other Safety Assessment Abnormalities Reported as SAEs and others. Any abnormal safety 
assessments (e.g., vital sign measurements), including those that worsen from baseline and are 


UAB IRB  
Approved 
18-Jan-2023 
 
felt to be clinically significant in the medical and scientific judgment of the investigator, are to 
be recorded as SAEs and others. 
The review and decision regarding altering or stopping the protocol will be performed by the 
Principal Investigator, DSMB, and the study physician at UAB. Reasons to stop the study 
include an unexpected incidence of AEs attributed to metoprolol. The principal investigator will 
review any AEs immediately following their occurrence and report them to the Institutional 
Review Board (IRB) in accordance with their guidelines. All SAEs will be reported by phone, 
fax, or email within 24 hours to both the IRB and DSMB by the study monitor (principal 
investigator and/or study physician at UAB) followed by a full written report within 10 
business/14 calendar days. 

ICF_002.pdf: 
Page 1 of 15
Dated:.11.30.2022
CONSENT FORM
TITLE OF RESEARCH:
Race, Natriuretic Peptides and Physiological Perturbations
IRB PROTOCOL NO.:
IRB-170214001
INVESTIGATOR:
Dr. Pankaj Arora, MD, FAHA
SPONSOR:
                                               National Institute of Health (NIH) 
           American Heart Association (AHA)
Purpose of the Research
We are asking you to take part in a research study.
We are asking you to join because you are a healthy subject between the ages of 
18-40 who has no history of cardiovascular disease, high blood pressure or 
diabetes or taking any medications for any of these conditions. The purpose of 
this study is to understand the difference in response to medications between 
healthy African Americans and healthy Caucasians. In addition, exercise 
increases natriuretic peptide (NP) levels. We will also compare the NP levels 
after exercise in African-American and Caucasians.
NPs are hormones produced by the heart to in response to stress on heart walls. 
NP levels are used to diagnose heart failure. African-Americans have lower NP 
levels as compared to Caucasians. This might contribute to increased rate of 
heart failure and death in African Americans. Beta-blocker therapy increases NP 
levels which benefits heart failure patients. But beta-blockers are less effective 
in African Americans compared to Caucasians in heart failure treatment. NP’s 
role in healthy individuals is not known.
We expect to enroll 40 healthy African Americans and 40 healthy Caucasians for
this study at University of Alabama at Birmingham.
Explanation of Procedures
This study will take place at following locations-

UAB Clinical Research Unit (CRU), located on 15th floor in Jefferson tower building (625 
19th Street South)

Physical Activity core (PAC), located on 2nd floor in the Webb-Mott Nutrition 
Science Building (1675 University Blvd.)

Outreach laboratory, located on 2nd floor in Spain Wallace building (620 19th 
Street South)

UAB Wallace Tumor Institute (WTI), PET/MR imaging suite, located in the basement of 
the Wallace Tumor Institute

UAB Center for Exercise Medicine (UCEM), located at 1313, 13th Street South
UAB IRB
Approved
18-Jan-2023
until
17-Jan-2024


Page 2 of 15
Dated:.11.30.2022
Study Visit #1 (Screening Visit):
You will be asked to come to the CRU for the screening visit. This visit will take about 2 hours. 
During this visit, we will get your consent and perform the following tests and procedures to 
see if you can take part in the main study:

Take your blood pressure three times. If your blood pressure is more than 140/90 or 
systolic blood pressure less than 100, you will not be able to continue in the study.

If your heart rate less than 60/minute, you will not be able to continue in the study.

Complete a questionnaire about personal information, past medical history, medications, family 
medical history, and rule out psychiatric illness. You will complete questionnaires to rule 
out psychiatric illness. Your response to the questionnaires will be reviewed before you 
leave. You may be approached to discuss your options and will be provided the following 
list of mental health resources in order to address issues of depression and/or domestic 
violence: 
1. National Network of Depression Centers: 
https://nndc.org/resource-links/; 1-800-273-8255.
2. National Domestic Violence Hotline: 
       https://www.thehotline.org/
3. Alabama Coalition Against Domestic Violence: 
       http://www.acadv.org/; 1.800-650-6522.
4. Crisis Center Birmingham: 
       https://www.crisiscenterbham.org/
5.
Mental Health Professionals in Birmingham: 
https://www.psychologytoday.com/us/psychiatrists/al/birmingham

Measure your height and weight.

If you are a female able to become pregnant, we will test your urine for pregnancy. 
Pregnant women cannot take part in this study.

Draw about 25 ml or 5 teaspoons of blood. We will do the following tests on your blood- NP 
levels, a chemistry panel (electrolytes, kidney function and glucose), complete blood count, 
and a liver function panel.

Schedule you to meet with a study nutritionist who will ask you about your dietary 
choices and practices.

Give you a food log to take home and write down what you eat and drink for the next 
few days.
The study doctor will review the results of these blood tests and tell you if you can be in the 
study or not. If you cannot join the study, the study doctor will tell you the reason as well. 
We will suggest follow-up with your primary care physician if this is the case.
If you can join the study and decide to continue in the study, we will ask for your convenient 
date and time, and schedule you for visits #2 and #3.
Prior to Study Visit #2
You will fast overnight (>6 hours) prior to this visit and will be required  not  to  drink caffeine 
and alcoholic beverages 24 hours prior to this visit


Page 3 of 15
Dated:.11.30.2022
Study Visit #2 (Baseline Visit/Food Pick-up)
Visit will last about 2 hours
You will come to the PAC/UCEM for this visit. We will determine your aerobic fitness/VO2max

You will pick up 3 days of meals from the CRU.

You will be provided a container for 24-hour urine collection. Urine sample will be 
tested for sodium, protein and creatinine levels.
We will ask you to eat a special study diet for 3 days prior to the study visit #3. The diet 
will include of 3 meals a day (breakfast, lunch and dinner) and snacks and will be given to 
you by the UAB CRU. While you are on this diet, we will ask you not to eat anything which is 
not given to you by the UAB CRU. In addition, we will give the meals to you at no cost. These 
meals will have all the nutrients required for a healthy diet.
(VO2 max stands for V - volume, O2 - oxygen, max – maximum. VO2 is the maximum amount of 
oxygen consumption measured during increasing exercise (for example on a treadmill). This 
oxygen consumption reflects the physical fitness of an individual.
(Instructions for 24-urine collection: Instruct the subject to empty bladder. Discard this specimen. 
Record time and date on specimen container. Collect all urine after this first voiding. Do not 
urinate directly into the 24-hour collection container. The specimen should be refrigerated 
during the collection period. The following morning (24 hours later), have the patient void, 
collect the urine and add this urine to the 24- hour specimen)
Prior to Study Visit #3
Three days prior to 3rd visit, you will consume the meals provided by the CRU. You will also be 
required to collect 24-hour urine and fast overnight (>6 hours) prior to this visit. We will also 
ask you not to drink alcohol and caffeine-containing beverages (such as coffee, tea, soft drinks, 
or energy drinks) during this time.
Study Visit #3 (Exercise Challenge Visit)
You will drop off the urine at the outreach lab or hand over to the research coordinator.
Then you will come to the PAC/UCEM. This visit will last about 3 hours. When you arrive at the PAC, 
we will:

Ask to lie down and rest for 30 minutes.

Take your vitals such as blood pressure and heart rate

Take your neck, arm, waist, hip and calf circumferences

Measure a skinfold thickness and arterial pulse

Perform exercise challenge test: You will wear a mask (to measure oxygen uptake and 
carbon dioxide production) and perform exercise. Exercise will start with a 4-minute 
warmup. Each subject will walk for 20 minutes and will undergo a 4-minute cool-down 
after the exercise.

Measure your blood pressure for 3 times during exercise.

Ask to rest for 30 minutes.

Ask you to keep a mask on initial 5 minutes


Page 4 of 15
Dated:.11.30.2022

Finger stick will be performed

Ask you to put on a mask just 5 minutes before the end of 30 minutes rest
Draw  15cc  or  3  teaspoons  of  blood  sample  4  times  (before  exercise  challenge, 
immediately after, 15 min and 30 min later). Blood samples will be tested for natriuretic 
peptide levels, insulin, and glucose.

Collect urine before and after the exercise challenge. Urine sample will be tested for 
sodium, protein and creatinine levels.

Provide you a container for 24-hour urine collection
Prior to Study Visit #4
Three-seven days after 3rd visit, you will need to come for 4th visit. Prior to this visit:

You will collect urine 24 hours prior to the visit

You will fast overnight (>6 hours) and will not drink caffeine and alcohol beverages 24 
hour prior to this visit
Study Visit #4

Visit will take about 2 hours

You will drop off the urine at the outreach lab. Urine sample will be tested for sodium, 
protein and creatinine levels.

Then, you will come to the CRU. When you arrive at the CRU:
o
BP and heart rate (HR) will be measured and. If BP is between (140/90 - 100/50) 
and HR is >60 than a two-week supply of metoprolol succinate (50mg/day) will 
be provided.
o
If you are a female able to become pregnant, we will test your urine for 
pregnancy. Pregnant women cannot take part in this study.
o
You will be asked to take a rest for 1 hour
o
20cc or 4 teaspoons of venous blood will be drawn. Blood samples will be tested 
for natriuretic peptide levels, insulin, glucose, renin and aldosterone.
o
You will be called by the study doctor to assess medicine side effects within 
7 days after this visit
Prior to Study Visit #5
You will fast overnight (>6 hours) prior to this visit, and not to drink caffeine and alcohol 
beverages 24 hour prior to this visit.
Study Visit #5

Two weeks after visit #4, you will come for this visit

Visit will take about 2 hours

You will come to the CRU for this visit, where we will:
o
Measure your BP and HR
o
You will be asked to take a rest for 1 hour
o
Draw 20ml or 4 teaspoons blood. Blood samples will be tested for 
natriuretic peptide levels, insulin, glucose, renin and aldosterone.
o
Assess compliance by doing a pill count and reviewing the calendar
o
Discuss side effects from the metoprolol use


Page 5 of 15
Dated:.11.30.2022
o
Provide metoprolol succinate (100mg/day) for 2 more weeks
o
You will be called by the study doctor to assess medicine side effects
within 7 days after this visit
Prior to Study Visit #6
You will fast overnight (>6 hours) prior to this visit, and not to drink caffeine and alcohol 
beverages 24 hour prior to this visit.
Study Visit #6

Two weeks after visit #5, you will come for this visit

Visit will take about 2 hours

You will come to the CRU for this visit, where we will:
o
Measure your BP and HR
o
You will be asked to take a rest for 1 hour
o
Draw 20ml or 4 teaspoons blood. Blood samples will be tested for 
natriuretic peptide levels, insulin, glucose, renin and aldosterone.
o
Assess compliance by doing a pill count and reviewing the calendar
o
Discuss side effects from the metoprolol use
o
Provide metoprolol succinate (200mg/day) for 2 more weeks
o
Provide you a container for 24 hour urine collection
o
You will be called by the study doctor to assess medicine side effects 
within 7 days after this visit
Study Visit #7

Two weeks after visit #6, you will come for this visit

Visit will take about 2 hours

You will drop off the urine at the outreach lab. Urine sample will be tested for sodium, 
protein and creatinine levels.

Then, you will come to the CRU, where we will:
o
Measure your BP and HR
o
You will be asked to take a rest for 1 hour
o
Draw 20ml or 4 teaspoons blood. Blood samples will be tested for 
natriuretic peptide levels, insulin, glucose, renin and aldosterone.
o
Assess compliance by doing a pill count and reviewing the calendar
o
Discuss side effects from the metoprolol use
(Modification in the study visits: At every visit, BP and HR will be measured. Metoprolol will 
be discontinued for any systolic BP < 80 mm Hg and HR < 40 beats/minute at visit #5 and visit
#6. If you develop intolerance or any side effects from increasing the dose of metoprolol, you 
will go back to the maximally tolerated last dose to finish the 6-week duration.)
Study Visit #8
One week after visit #7, you will come to CRU for 8th/final visit. After 15 min of rest, BP and HR 
will be measured (three times) to assess your well-being. This visit will take about 2 hours. At 
the end of this visit, your participation will be complete.


Page 6 of 15
Dated:.11.30.2022
Summary table of the study visits:
Study visit
Timing of the study visit
Location
Visit 1
Day 1
CRU
Visit 2
Within 7-10 days of visit 1
PAC/UCEM and CRU (Food Pick 
Visit 3
4 days after visit 3
PAC/UCEM
Visit 4
Within 3-7 days after visit 3
CRU
Visit 5
2 weeks after visit 4
CRU
Visit 6
2 weeks after visit 5
CRU
Visit 7
2 weeks after visit 6
CRU
Visit 8
1 week after visit 7
CRU
Risks and Discomforts
Potential breach of confidentiality
There is a slight risk that your private health information may be seen by others. But, safety 
measures will be taken to reduce such a problem.
Risks of Blood Draw
You may have a small amount of bleeding or a bruise may develop. Sometimes, a person feels 
faint or lightheaded when his/her blood is drawn. Rarely an infection can develop; it can be 
treated. Risk is lowered by keeping skilled person for blood draw.
Risks of Fasting
For the study, you will be asked to fast (no food to eat) for more than 6 hours overnight. Long 
hours of fasting cause hypovolemia (a decreased volume of circulating blood in the body) and 
can make you dizzy, faint, or irritable.
Risk in Food Preparation
There is a small risk that food may be not be prepared right. People who consume food that is 
not prepared right may experience nausea, vomiting, or diarrhea. However, the CRU metabolic 
kitchen follows correct policies and procedures to ensure food safety.
Risks of Metoprolol
Cardiovascular (low heart rate, cold extremities, heart failure, hypotension); dermatologic 
(pruritus, rash); gastrointestinal (constipation, diarrhea, indigestion, nausea); neurologic 
(dizziness, fatigue, headache); psychiatric (depression); respiratory (dyspnea, wheezing, 
bronchospasm).


Page 7 of 15
Dated:.11.30.2022
Risk of driving and operating equipment during metoprolol period
Metoprolol may cause drowsiness, fatigue, dizziness or lightheadedness in some people. If any 
of these occur, do not drive, operate machinery or do anything else that could be dangerous.
Risks of Caffeine Withdrawal
There is a small risk that people who take caffeine regularly, may show withdrawal symptoms 
like headache, fatigue or drowsiness, depressed mood or irritability, difficulty concentrating, 
and flulike symptoms such as nausea or muscle pain.
Risks of Alcohol Withdrawal
There is a small risk of alcohol withdrawal in people who take alcohol regularly. They may show 
mild symptoms such as sleep disturbances and anxiety to severe and life-threatening symptoms 
such as delirium, hallucinations, and autonomic instability.
Risks of Exercise
Risk of exercising include strains and tears, inflammation, stress fractures, tendonitis, heart 
problems such as arrhythmias, sudden cardiac arrest, and heart attack. People who do not 
exercise on a regular basis are more likely to suffer injuries when engaging in such activity.
Benefits
You will not benefit from taking part in this study. The results of this research study may help us 
understand different racial response to cardiovascular risk.
Alternatives
Your alternative is to not participate in this research study.
Confidentiality
Information obtained about you for this study will be kept confidential to the extent allowed by 
law. However, research information that identifies you may be shared with the UAB 
Institutional Review Board (IRB) and others who are responsible for ensuring compliance with 
laws and regulations related to research, Department of Medicine, Division of Cardiology, the 
Office for Human Research Protections  (OHRP)  and the study sponsor, NIH and AHA. The 
information from the research may be published for scientific purposes; however, your identity 
will not be given out. Information obtained during the course of the study which in the opinion of 
the investigator(s), suggests that you may be at significant risk of harm to yourself or others will 
be reportable to a third party in the interest of protecting the rights and welfare of those at 
potential risk.


Page 8 of 15
Dated:.11.30.2022
If any part of this study takes place at University of Alabama Hospital this consent document 
will be placed in your file at that facility. The document will become part of your medical record 
chart. Information relating to this study, including your name, medical record number, date of 
birth and social security number, may be shared with the billing offices of UAB and UAB 
Health System affiliated entities so that the costs for clinical services can be appropriately paid 
for by either the study account or by the patient/patient’s insurance.
A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. 
Law. This website will not include information that can identify you. At most, the website will 
include a summary of the results. You can search this website at any time.
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it 
illegal for health insurance companies, group health plans, and some employers to discriminate 
against you based on your genetic information. This law generally will protect you in the following 
ways:

Health insurance companies and group health plans may not request your genetic 
information that we get from this research.

Health insurance companies and group health plans may not use your genetic information 
when making decisions regarding your eligibility or premiums.

Employers with 15 or more employees may not use your genetic information that we get 
from this research when making a decision to hire, promote, or fire you or when setting 
the terms of your employment.
Be aware that this federal law does not protect you against genetic discrimination by companies 
that sell life insurance, disability insurance, or long-term care insurance, nor does it protect you 
against genetic discrimination by all employers.
Voluntary Participation and Withdrawal
Whether or not you take part in this study is your choice. There will be no penalty if you decide 
not to be in the study. If you decide not to be in the study, you will not lose any benefits you 
are otherwise owed. You are free to withdraw from this research study at any time. Your choice 
to leave the study will not affect your relationship with this institution.
You may be removed from the study without your consent if the sponsor ends the study, if the 
study doctor decides it is not in the best interest of your health, or if you are not following the 
study rules.
If you are a UAB student or employee, taking part in this research is not a part of your UAB class 
work or duties. You can refuse to enroll, or withdraw after enrolling at any time before the 
study is over, with no effect on your class standing, grades, or job at UAB. You will not be 
offered or receive any special consideration if you take part in this research.


Page 9 of 15
Dated: 11.30.2022
Cost of Participation
There will be no cost to you for taking part in this study.
Payment for Participation in Research
You will receive $25 for screening visit, $50 for 2nd, 3rd, 4th, 5th 6th and 7th visits (each visit), 
and $25 for 8th/final visit in about 4 weeks after study visit. This will be a total of $350. Ask the 
study staff about the method of payment that will be used for this study (e.g., check, direct 
deposit).
We will also reward you for a successful referral. We will ask you to share our 
study information with your friends or family members. For a successful 
enrollment and randomization of your friend or member of your family, we 
will reward you with a $25 referral reward in the form of cash or through UAB 
ClinCard. 
Payment for Research-Related Injuries
UAB and the study sponsors, NIH and AHA have not provided for any payment if you are 
harmed as a result of taking part in this study. If such harm occurs, treatment will be provided. 
However, this treatment will not be provided free of charge.
Significant New Findings
You will be told by your doctor or the study staff if new information becomes available that 
might affect your choice to stay in the study.
Optional Research
Please note: This section of the consent form is about optional research that is being done 
with people who are taking part in this study. You may take part in this optional research if 
you want to. You can still be a part of this study even if you say no to take part in any of the 
optional research.
You can say "yes" or "no" to each of the following studies. Please mark your choice for each 
study.


Page 10 of 15
Dated: 11.30.2022
Future Contact
We would like your permission to contact you about being in future research projects related 
cardiovascular and metabolic diseases. Based upon result of this visit and test results, we may 
contact you by phone or in writing about future studies. You can say no to participate in these 
studies.
I agree to allow you to contact me about other studies
 
I DO NOT agree to allow you to contact me about other studies
Genetic Testing
We would like to request your permission to collect ½ tablespoon of whole blood to extract DNA 
and store that for future studies. We are not going analyze your DNA study information for this 
protocol. The DNA that composes of your genes will be analyzed and that data, which is referred 
to your genotype or complete genetic makeup, compared to your phenotype, which consists of 
your observable traits, characteristics, and diseases in the future.
There are multiple genes involved in the regulation of human blood pressure. Until recently, no 
common genetic variants had been found which were related to human blood pressure. A genetic 
variant is a change in a particular gene that may affect the health of the person who has it.
Recently, researchers have discovered a genetic variant which is present in about 1 out of 10 
people and is related to blood pressure and to levels of natriuretic peptides.
We may pursue to study these genetic variates in the future. The future research related to these 
genetic variates may be conducted by Dr. Pankaj Arora or other researchers after the IRB’s 
approval for their research. How your identity relates to these specimens will be coded and only 
Dr. Pankaj Arora will have access to it.
The results related to these future studies will not be disclosed to you or your doctor. 
Initial your choice below:
 
I agree to allow you to store DNA to test for genetic variants.
 
I DO NOT agree to allow you to store DNA you to test for genetic variants.
Gene Expression  
We would like to request your permission to collect ½ teaspoon of whole blood to extract RNA and 
store that for the current study. Through RNA extraction, we are going to see gene expression of 
certain natriuretic peptide family of genes in whole blood. The principal role of RNA is to act as a 
messenger carrying instructions from DNA for controlling the synthesis of proteins. 
Do you agree to let us store RNA from your blood and contact you for the future studies related to 
genetic variants?


Page 11 of 15
Dated: 11.30.2022
Initial your choice below:
_____________ I agree to allow you to store RNA to test for its expression in the current study.                               
_____________ I DO NOT agree to allow you to store RNA to test for its expression in the current 
study.  
                                                                                   
Positron Emission Tomography and Magnetic Resonance Imaging
Positron emission tomography (PET) is a type of imaging test that uses a small amount of 
radioactive material injected into your vein to see how cells or tissues are functioning. It is 
combined with a Magnetic Resonance Imaging (MRI) (a test that uses magnetic fields and radio 
waves to generate images of the inside of your body) in one machine so doctors can better see 
the structures the PET agent goes to. Before the scan, you will have to follow preparation 
instructions including not eating for 6 hours before the test. After the PET agent is injected, you 
will wait 45-60 minutes before being scanned. The scan will take 20 minutes, and you must lie 
still during that time.
In this study you will have a MRI exam. A magnetic resonance imaging (MRI) exam is a test that 
uses magnetic fields and radio waves to generate images of the inside of your body.
You will be placed inside a scanner and asked to lie still for about 20 minutes. This is a noisy 
exam; you will be given earplugs to protect your hearing.
We are performing imaging solely for the research purposes described above. It is not a clinical 
scan intended for diagnostic or therapeutic purposes. Under no circumstance will the 
investigator, research staff, or imaging staff interpret the scan as normal or abnormal. They are 
unable to make any medical comments about your scan. The scan will not be looked at or read 
for any healthcare treatment or diagnostic purpose. If you want your scan to be reviewed by a 
physician so the physician can look for medical issues, you can request a copy of your scan. We 
will provide an electronic copy at no charge.
There will be no cost to you for taking part in this optional research. The NIH is funding this study 
and will cover the cost of the study.
Risks of Positron Emission Tomography (PET)
Because the doses of radiotracer administered are small, diagnostic nuclear medicine  procedures 
result in low radiation exposure, acceptable for diagnostic exams. Thus, the radiation risk is very 
low compared with the potential benefits. Nuclear medicine diagnostic procedures have been 
used for more than five decades, and there are no known long-term adverse effects from such 
low-dose exposure. Allergic reactions to radiopharmaceuticals may occur but are extremely rare 
and are usually mild. Nevertheless, you should inform the nuclear medicine personnel of any 
allergies you may have or other problems that may have occurred during a previous nuclear 
medicine exam. Injection of the radiotracer may cause slight pain and redness which should 


Page 12 of 15
Dated: 11.30.2022
rapidly resolve. Women should always inform their physician or radiology technologist if there is 
any possibility that they are pregnant or if they are breastfeeding their baby.
In this study, you will be exposed to some radiation from the PET scans. The radiation from the 
each scan is approximately equal to 2 years of exposure to natural background radiation.
Background radiation is radiation normally received from sources such as cosmic rays and 
natural radioactivity in building materials and the ground. There is a small
risk that the 
radiation may cause cancer or other radiation effects in several years.
Risks of Magnetic Resonance Imaging (MRI)
MRI uses a strong magnetic field and non-ionizing radiofrequency pulses to generate images of 
the human body. These images will provide information about the type and relative amount of a 
particular tissue present in participant’s body. In this study, we are particularly focused on the 
neck, shoulders and chest MRI has negligible risks for most people; however, if you have any 
metal objects in your body MRI may not be safe for you and you will not be allowed to take part 
in this study.
During the exam, you will be in a small, enclosed space. If you suffer from a fear of enclosed 
spaces, or experience extreme anxiety during the exam, please let the research staff know 
immediately.
Thermal Imaging
If you agree to participate with the PET/ MRI imaging, we will take an infrared picture of your
body just prior to the PET/MRI. This is a picture taken with a special camera called a 
thermographic or infrared camera. We are taking this picture to detect your body surface 
temperature. There are no additional risks involved with this noninvasive infrared picture.
Initial your choice below:
 
I agree to participate with PET/MRI imaging.
 
I DO NOT agree to participate with PET/MRI imaging.
If you agree to participate with PET/MRI imaging, you will come to the UAB Wallace Tumor 
Institute (WTI), PET/MR imaging suite, located in the basement of the Wallace Tumor Institute 
on visit # 4 and 7 after completing CRU visit.
Summary table of the study visits (if you agree to participate in PET/MRI imaging):
Study visit
Timing of the study visit
Location
Visit 1
Day 1
CRU
Visit 2
Within 7-10 days of visit 1
PAC/UCEM and CRU (Food Pick 
Visit 3
4 days after visit 3
PAC/UCEM
Visit 4
Within 3-7 days after visit 3 + 
PET/MRI imaging
CRU and WTI
Visit 5
2 weeks after visit 4
CRU


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Visit 6
2 weeks after visit 5
CRU
Visit 7
2 weeks after visit 6 + 
PET/MRI imaging
CRU and WTI
Visit 8
1 week after visit 7
CRU
Payment for Participation in PET/MRI imaging
You will receive an additional $100 ($50 for each visit) for participating in this optional study.
Questions
If you have any questions, concerns, or complaints about the research  or  a  research- related 
injury including available treatments, you may contact Dr. Vibhu Parcha, Dr. Nirav Patel  and  
Dr. Pankaj Arora. They will be glad to answer any question. Dr. Parcha’s number is 205-
934-7936, Dr. Patel’s number is 205-934-6058 and Dr. Arora’s number is 205-936-6630. Dr. 
Patel may also be paged after hours at 205-435- 5866. You may also contact the study 
coordinator, Nehal Vekariya at 205-934-7173.
If you have questions about your rights as a research participant, or concerns or complaints 
about the research, you may contact the UAB Office of the IRB (OIRB) at (205) 934-3789 or 
toll free at 1-855-860-3789. Regular hours for the OIRB are 8:00 a.m. to 5:00
p.m.  CT,  Monday through Friday. You may also call this number in the event the research
staff cannot be reached or you wish to talk to someone else.
Legal Rights
You are not waiving any of your legal rights by signing this informed consent document.
Storage of Specimens for Future Use
After we have processed your blood samples for this research study we would like to store 
any leftover blood at UAB for future research related to cardiovascular and metabolic disease. 
The future research may be conducted by Dr. Pankaj Arora or by other researchers that 
obtain IRB approval for their research. The specimens will be labeled with a code that only 
Dr. Pankaj Arora can link back to you. Results of any future research  will  not be given to 
you or your doctor. The specimens obtained from you in this research may help in the 
development of a future commercial product. There are no plans to provide financial 
compensation to you should this occur.
You do not have to agree to allow your blood specimens to be stored in order to be part of this 
study. You may request at any time that your research samples be removed from storage and 


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Dated: 11.30.2022
not be used for future research. If you decide you want your samples removed, you  may contact 
Nirav Patel at npatel@uabmc.edu or 205-934-6058 or Dr. Pankaj Arora at the University of 
Alabama at Birmingham at parora@uabmc.edu. Once the request is received, and if your 
samples have not already been used for other research, they will be destroyed. If you do not 
make such a request, your specimens will be stored indefinitely or until used.
Initial your choice below:
 
I agree to allow my samples to be kept and used for future research on hypertension.
 
I do not agree to allow my samples to be kept and used for future research.
Signatures
Your signature below indicates that you have read (or been read) the information provided 
above and agree to participate in this study. You will receive a copy of this signed consent form.
Signature of Participant
Date
Signature of Person Obtaining Informed Consent
Date


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Dated: 11.30.2022
University of Alabama at Birmingham 
AUTHORIZATION FORUSE/DISCLOSURE OF
PROTECTED HEALTH INFORMATION (PHI) FOR RESEARCH
Participant Name:
UAB IRB Protocol Number: IRB-170214001 
Research Protocol:  Race, Natriuretic Peptides and 
Physiological Perturbations
Principal Investigator: Pankaj Arora, MD, FAHA
Peptide Response to Exercise and Beta-blockers.
Sponsor: UAB Division of Cardiology, NIH, American Heart 
Association
What is the purpose of this form? You are being asked to sign this form so that UAB may use and release your protected 
health information for research. Participation in research is voluntary. If you choose to participate in the research, you must 
sign this form so that your protected health information may be used for the research.
Why do the researchers want my protected health information? The researchers want to use your protected health information 
as part of the research protocol listed above and as described to you in the informed consent.
What protected health information do the researchers want to use? All medical information, including but not limited to 
information and/or records of any diagnosis or treatment of disease or condition, which may include sexually transmitted 
diseases (e.g., HIV, etc.) or communicable diseases, drug/alcohol dependency, etc.; all personal identifiers, including but not 
limited to your name, social security number, medical record number, date of birth, dates of service, etc.; any past, present, 
and future history, examinations, laboratory results, imaging studies and reports and treatments of whatever kind, including 
but not limited to drug/alcohol treatment, psychiatric/psychological treatment; financial/billing information, including but not 
limited to copies of your medical bills, and any other information related to or collected for use in the research protocol, 
regardless of whether the information was collected for research or non-research (e.g., treatment) purposes.
Who will disclose, use and/or receive my protected health information? All Individuals/entities listed in the informed consent 
documents, including but not limited to, the physicians, nurses and staff and others performing services related to the research 
(whether at UAB or elsewhere); other operating units of UAB, HSF, UAB Highlands, Children’s of Alabama, Eye Foundation 
Hospital, and the Jefferson County Department of Health, as necessary for their operations; the IRB and its staff; the sponsor of 
the research and its employees and agents, including any CRO; and any outside regulatory agencies, such as the Food and Drug 
Administration, providing oversight or performing other legal and/or regulatory functions for which access to participant 
information is required.
How will my protected health information be protected once it is given to others? Your protected health information that is 
given to the study sponsor will remain private to the extent possible, even though the study sponsor is not required to follow 
the federal privacy laws. However, once your information is given to other organizations that are not required to follow federal 
privacy laws, we cannot assure that the information will remain protected.
How long will this Authorization last? Your authorization for the uses and disclosures described in this Authorization does not 
have an expiration date.
Can I cancel this Authorization? You may cancel this Authorization at any time by notifying the Principal Investigator, in 
writing, referencing the research protocol and IRB Protocol Number. If you cancel this Authorization, the study doctor and staff 
will not use any new health information for research. However, researchers may continue to use the protected health information 
that was provided before you cancelled your authorization.
Can I see my protected health information? You have a right to request to see your protected health information. However, to 
ensure the scientific integrity of the research, you will not be able to review the research information until after the research 
protocol has been completed.
Signature of participant:
Date:  
or participant's legally authorized representative:
Date:  
Printed Name of participant’s representative:  
Relationship to the participant: