Clinical trial NCT04752293: Pediatric Hypertension and the Renin-Angiotensin SystEm (PHRASE)
Official title: Pediatric Hypertension and the Renin-Angiotensin SystEm (PHRASE): The Role of Angiotensin-(1-7) in Hypertension and Hypertension-Induced Heart and Kidney Damage
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hypertension
Left Ventricular Hypertrophy
Left Ventricular Dysfunction
Left Atrial Dilatation
Left Ventricular Diastolic Dysfunction
Kidney Diseases
Kidney Injury
Kidney Dysfunction
Sodium Urine High
Blood Pressure Disorders
Uric Acid Retention
Angiotensin Hypertension
Autonomic Dysfunction
Autonomic Imbalance
Pediatric Kidney Disease
Pediatric Obesity
Proteinuria
Albuminuria
Keywords: High Blood Pressure
Elevated Blood Pressure
Hypertension
Pediatric Hypertension
Target Organ Damage
Left Ventricular Hypertrophy
Albuminuria
Uric Acid
Klotho
Fibroblast Growth Factor 23
Renin-Angiotensin-Aldosterone System
Renin-Angiotensin System
Angiotensin-(1-7)
Angiotensin II
Angiotensin-Converting Enzyme 2
Angiotensin-Converting Enzyme
Causal Inference
Causal Mediation Analysis
Sensitivity Analysis
Predictive Analysis
Left Ventricular Diastolic Dysfunction
Kidney Injury
Heart Rate Variability
Sodium
Pediatric Obesity
Lifecourse
Kidney Function
Ambulatory Blood Pressure Monitoring
Echocardiogram
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-02-12
Enrollment: 125
Sex: ALL
Minimum age (years): 7
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hypertension Cohort: Participants will be recruited from among new patients referred to the Hypertension Clinic at Brenner Children's Hospital. Patient population at this clinic, which sees over 300 new patients/year, is 55% White, 25% Black, 16% Hispanic, and 62% male. Goal is to enroll 100 participants over a 2-year period.

Control Cohort: Participants for this cohort will be recruited from among healthy patients seen at local pediatrics practices. Goal is to enroll 25 participants over a 2-year period, frequency-matched to the Hypertension Cohort on age, self-identified race, and sex.

Brief summary: Studying the causal roles of components of the renin-angiotensin-aldosterone system (including angiotensin-(1-7) (Ang-(1-7)), angiotensin-converting enzyme 2 (ACE2), Ang II, and ACE), uric acid, and klotho in pediatric hypertension and related target organ injury, including in the heart, kidneys, vasculature, and brain. Recruiting children with a new hypertension diagnosis over a 2-year period from the Hypertension and Pediatric Nephrology Clinics affiliated with Brenner Children's Hospital at Atrium Health Wake Forest Baptist and Atrium Health Levine Children's Hospital. Healthy control participants will be recruited from local general primary care practices. Collecting blood and urine samples to analyze components of the renin-angiotensin-aldosterone system (Ang-(1-7), ACE2, Ang II, ACE), uric acid, and klotho, and measuring blood pressure, heart structure and function, autonomic function, vascular function, and kidney function at baseline, year 1, and year 2. Objectives are to investigate phenotypic and treatment response variability and to causally infer if Ang-(1-7), ACE2, Ang II, ACE, uric acid, and klotho contribute to target organ injury due to hypertension.

Detailed description: This longitudinal prospective cohort study is recruiting children and adolescents aged 7-18 years with newly diagnosed primary hypertension over a 2-year period from the Hypertension and Pediatric Nephrology Clinics affiliated with Brenner Children's Hospital at Atrium Health Wake Forest Baptist, which sees over 300 new patients a year, and the Pediatric Nephrology Clinic at Atrium Health Levine Children's Hospital (Hypertension Cohort). Also recruiting healthy control participants aged 7-18 years with normal blood pressure from local primary care practices (Control Cohort). Collecting blood and urine to analyze Ang-(1-7), ACE2, Ang II, ACE, uric acid, and klotho and measuring pediatric-specific outcomes (blood pressure (casual and ambulatory monitoring), indices of heart structure and function on echocardiogram (left ventricular systolic and diastolic function, left ventricular hypertrophy, etc.), kidney function (creatinine, estimated glomerular filtration rate, albuminuria, proteinuria, urine sodium/potassium), autonomic function (heart rate variability, blood pressure variability, baroreflex sensitivity), and vascular function (arterial stiffness, augmentation index)) at baseline and year 1 (Hypertension Cohort and Control Cohort) and year 2 (Hypertension Cohort). The objectives are to investigate if Ang-(1-7), ACE2, Ang II, and ACE identify phenotypic and treatment response variability and to causally infer if Ang-(1-7), ACE2, Ang II, ACE, uric acid, and klotho contribute to target organ injury, with these Specific Aims:

Aim 1:

(1) Determine if plasma Ang-(1-7) or urine Ang-(1-7)/creatinine differ between the Hypertension vs. Control Cohorts and (2) assess if plasma Ang-(1-7) or urine Ang-(1-7)/creatinine mediate the effect of lisinopril-induced blood pressure reduction on the outcomes (change in heart function and structure, autonomic function, vascular function, and kidney function).

Hypothesis 1a: Baseline Ang-(1-7) is lower in the Hypertension vs. Control Cohort.

Hypothesis 1b: Increased Ang-(1-7) levels over time mediate the effect of lisinopril-induced decreased blood pressure on improved outcomes over 2 years in the Hypertension Cohort.

Aim 2:

(1) Evaluate if plasma Ang-(1-7) or urine Ang-(1-7)/creatinine predict treatment response in participants in the Hypertension Cohort (change in casual blood pressure, ambulatory blood pressure, heart function/structure, autonomic function, vascular function, and kidney function); (2) compare to plasma renin activity and aldosterone; and (3) employ sensitivity analyses to quantify the impact of unmeasured confounding.

Hypothesis 2: Lower baseline Ang-(1-7) predicts greater outcome improvements in the Hypertension Cohort with lower unmeasured confounding and with greater predictive ability compared to plasma renin activity and aldosterone.

Aim 3:

Determine if plasma Ang-(1-7) or urine Ang-(1-7)/creatinine mediate the effects of uric acid and klotho on the outcomes in participants in the Hypertension Cohort. (1) Apply causal mediation to estimate if plasma Ang-(1-7) mediates the effects of uric acid on the outcomes (change in casual blood pressure, ambulatory blood pressure, heart function/structure, autonomic function, and vascular function). (2) Apply causal mediation to estimate if urine Ang-(1-7)/creatinine mediates the effects of klotho on the outcomes (change in casual blood pressure, ambulatory blood pressure, and kidney function).

Hypothesis 3a: Lower plasma Ang-(1-7) mediates the effect of high uric acid on the outcomes in the Hypertension Cohort.

Hypothesis 3b: Lower urine Ang-(1-7)/creatinine mediates the effect of low klotho on the outcomes in the Hypertension Cohort.

Anticipated results have great potential to impact patient care by establishing Ang-(1-7), ACE2, Ang II, and ACE as biomarkers of treatment response, by establishing how Ang-(1-7) and other components of the renin-angiotensin-aldosterone system change in response to an ACE inhibitor, by indicating which patients would benefit most from ACE inhibitors, by identifying novel etiologies of hypertension centered on alterations to the renin-angiotensin-aldosterone system, uric acid, and klotho, and by leading to novel treatments. Indeed, these have been questions of great interest during the COVID-19 pandemic, as ACE2 is the binding site for Severe acute respiratory syndrome (SARS)-CoV-2. Ultimately, the results from this study will improve patient outcomes by promoting cardiovascular health and preventing cardiovascular disease across the lifecourse.

Eligibility criteria: INCLUSION CRITERIA: HYPERTENSION COHORT

* 7-18 years of age at time of enrollment
* Confirmed new diagnosis of primary hypertension: no identifiable secondary cause, referred to hypertension or nephrology clinic

  * Age \<13 years: BP ≥95th %ile or ≥130/80 mmHg (whichever is lower)
  * Age ≥13 years: BP ≥130/80 mmHg
* Participants and their caregivers must be willing and able to commit to completing the study assessments

EXCLUSION CRITERIA: HYPERTENSION COHORT

* \<7 years or \>18 years of age at time of enrollment
* BP confirmed as normal or in the elevated BP category based on ≥3 prior office BP measurements on separate days;

  * Age \<13 years: BP \<95th %ile or \<130/80 mmHg (whichever is lower)
  * Age ≥13 years: BP \<130/80 mmHg
* A confirmed secondary cause of hypertension
* Confounding medical condition (heart or kidney disease \[except hypertension-associated heart changes on echocardiogram or albuminuria\], vascular/inflammatory disease, or diabetes)
* Inability to complete study assessments
* Non-English/Spanish speakers
* Current pregnancy
* Ward of the State

INCLUSION CRITERIA: CONTROL COHORT

* 7-18 years of age at time of enrollment
* Normal BP based on ≥3 prior office BP measurements on separate days;

  * Age \<13 years: BP \<90th %ile or \<120/80 mmHg (whichever is lower)
  * Age ≥13 years: BP \<120/80 mmHg
* Participants and their caregivers must be willing and able to commit to completing the study assessments

EXCLUSION CRITERIA: CONTROL COHORT

* \<7 or \>18 years of age at time of enrollment
* Elevated BP or hypertension, based on ≥3 prior office BP measurements on separate days:

  * Age \<13 years: BP ≥90th %ile or ≥120/80 mmHg (whichever is lower)
  * Age ≥13 years: BP ≥120/80 mmHg
* History of elevated BP or hypertension
* Current use of BP-lowering medications
* Confounding medical condition (heart or kidney disease, vascular/inflammatory disease, or diabetes)
* Inability to complete study assessments
* Non-English/Spanish speakers
* Current pregnancy
* Ward of the State

Primary outcomes:
measure: Baseline Urine Angiotensin-(1-7)/Creatinine Ratio
timeFrame: Baseline
measure: Change in Urine Angiotensin-(1-7)/Creatinine Ratio
timeFrame: Baseline through 2 years
measure: Baseline Urine Angiotensin II/Angiotensin-(1-7) Ratio
timeFrame: Baseline
measure: Change in Urine Angiotensin II/Angiotensin-(1-7) Ratio
timeFrame: Baseline through 2 years
measure: Baseline Plasma Angiotensin-(1-7) Level
timeFrame: Baseline
measure: Change in Plasma Angiotensin-(1-7) Level
timeFrame: Baseline through 2 years
measure: Baseline Plasma Angiotensin II/Angiotensin-(1-7) Ratio
timeFrame: Baseline
measure: Change in Plasma Angiotensin II/Angiotensin-(1-7) Ratio
timeFrame: Baseline through 2 years
measure: Baseline Serum Uric Acid Level
timeFrame: Baseline
measure: Change in Serum Uric Acid Level
timeFrame: Baseline through 2 years
measure: Baseline Plasma Klotho Level
timeFrame: Baseline
measure: Change in Plasma Klotho Level
timeFrame: Baseline through 2 years
measure: Baseline Urine Klotho/Creatinine Ratio
timeFrame: Baseline
measure: Change in Urine Klotho/Creatinine Ratio
timeFrame: Baseline through 2 years
measure: Baseline Manual Systolic Blood Pressure
timeFrame: Baseline
measure: Change in Manual Systolic Blood Pressure
timeFrame: Baseline through 2 years
measure: Baseline Manual Diastolic Blood Pressure
timeFrame: Baseline
measure: Change in Manual Diastolic Blood Pressure
timeFrame: Baseline through 2 years
measure: Baseline Manual Systolic Blood Pressure Z-score
timeFrame: Baseline
measure: Change in Manual Systolic Blood Pressure Z-score
timeFrame: Baseline through 2 years
measure: Baseline Manual Diastolic Blood Pressure Z-score
timeFrame: Baseline
measure: Change in Manual Diastolic Blood Pressure Z-score
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Systolic Blood Pressure 24-Hour Mean
timeFrame: Baseline
measure: Change in Ambulatory Systolic Blood Pressure 24-Hour Mean
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Diastolic Blood Pressure 24-Hour Mean
timeFrame: Baseline
measure: Change in Ambulatory Diastolic Blood Pressure 24-Hour Mean
timeFrame: Baseline through 2 years
measure: Baseline Left Ventricular Mass Height Index
timeFrame: Baseline
measure: Change in Left Ventricular Mass Height Index
timeFrame: Baseline through 2 years
measure: Baseline Left Ventricular Mass Body Surface Area Index
timeFrame: Baseline
measure: Change in Left Ventricular Mass Body Surface Area Index
timeFrame: Baseline through 2 years
measure: Baseline Left Ventricular Hypertrophy
timeFrame: Baseline
measure: Change in Left Ventricular Hypertrophy
timeFrame: Baseline through 2 years
measure: Baseline Urine Albumin/Creatinine Ratio
timeFrame: Baseline
measure: Change in Urine Albumin/Creatinine Ratio
timeFrame: Baseline through 2 years
measure: Baseline Albuminuria
timeFrame: Baseline
measure: Change in Albuminuria
timeFrame: Baseline through 2 years
measure: Baseline Serum Creatinine Level
timeFrame: Baseline
measure: Change in Serum Creatinine Level
timeFrame: Baseline through 2 years
measure: Baseline Estimated Glomerular Filtration Rate
timeFrame: Baseline
measure: Change in Estimated Glomerular Filtration Rate
timeFrame: Baseline through 2 years
measure: Baseline Urine Sodium Concentration
timeFrame: Baseline
measure: Change in Urine Sodium Concentration
timeFrame: Baseline through 2 years
measure: Baseline Urine Sodium/Potassium Ratio
timeFrame: Baseline
measure: Change in Urine Sodium/Potassium Ratio
timeFrame: Baseline through 2 years
measure: Baseline Plasma Renin Activity
timeFrame: Baseline
measure: Change in Plasma Renin Activity
timeFrame: Baseline through 2 years
measure: Baseline Serum Aldosterone Level
timeFrame: Baseline
measure: Change in Serum Aldosterone Level
timeFrame: Baseline through 2 years
Secondary outcomes:
measure: Baseline Urine Angiotensin II/Creatinine Ratio
timeFrame: Baseline
measure: Change in Urine Angiotensin II/Creatinine Ratio
timeFrame: Baseline through 2 years
measure: Baseline Urine Angiotensin-Converting Enzyme 2 Level
timeFrame: Baseline
measure: Change in Urine Angiotensin-Converting Enzyme 2 Level
timeFrame: Baseline through 2 years
measure: Baseline Urine Angiotensin-Converting Enzyme Level
timeFrame: Baseline
measure: Change in Urine Angiotensin-Converting Enzyme Level
timeFrame: Baseline through 2 years
measure: Baseline Urine Angiotensin-Converting Enzyme/Angiotensin-Converting Enzyme 2 Ratio
timeFrame: Baseline
measure: Change in Urine Angiotensin-Converting Enzyme/Angiotensin-Converting Enzyme 2 Ratio
timeFrame: Baseline through 2 years
measure: Baseline Plasma Angiotensin II Level
timeFrame: Baseline
measure: Change in Plasma Angiotensin II Level
timeFrame: Baseline through 2 years
measure: Baseline Serum Angiotensin-Converting Enzyme 2 Level
timeFrame: Baseline
measure: Change in Serum Angiotensin-Converting Enzyme 2 Level
timeFrame: Baseline through 2 years
measure: Baseline Serum Angiotensin-Converting Enzyme Level
timeFrame: Baseline
measure: Change in Serum Angiotensin-Converting Enzyme Level
timeFrame: Baseline through 2 years
measure: Baseline Serum Angiotensin-Converting Enzyme/Angiotensin-Converting Enzyme 2 Ratio
timeFrame: Baseline
measure: Change in Serum Angiotensin-Converting Enzyme/Angiotensin-Converting Enzyme 2 Ratio
timeFrame: Baseline through 2 years
measure: Baseline Hyperuricemia
timeFrame: Baseline
measure: Change in Hyperuricemia
timeFrame: Baseline through 2 years
measure: Baseline Manual Blood Pressure Classification
timeFrame: Baseline
measure: Change in Manual Blood Pressure Classification
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Systolic Blood Pressure 24-Hour Load
timeFrame: Baseline
measure: Change in Ambulatory Systolic Blood Pressure 24-Hour Load
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Diastolic Blood Pressure 24-Hour Load
timeFrame: Baseline
measure: Change in Ambulatory Diastolic Blood Pressure 24-Hour Load
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Systolic Blood Pressure 24-Hour Index
timeFrame: Baseline
measure: Change in Ambulatory Systolic Blood Pressure 24-Hour Index
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Diastolic Blood Pressure 24-Hour Index
timeFrame: Baseline
measure: Change in Ambulatory Diastolic Blood Pressure 24-Hour Index
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Systolic Blood Pressure Awake Mean
timeFrame: Baseline
measure: Change in Ambulatory Systolic Blood Pressure Awake Mean
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Diastolic Blood Pressure Awake Mean
timeFrame: Baseline
measure: Change in Ambulatory Diastolic Blood Pressure Awake Mean
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Systolic Blood Pressure Awake Load
timeFrame: Baseline
measure: Change in Ambulatory Systolic Blood Pressure Awake Load
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Diastolic Blood Pressure Awake Load
timeFrame: Baseline
measure: Change in Ambulatory Diastolic Blood Pressure Awake Load
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Systolic Blood Pressure Awake Index
timeFrame: Baseline
measure: Change in Ambulatory Systolic Blood Pressure Awake Index
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Diastolic Blood Pressure Awake Index
timeFrame: Baseline
measure: Change in Ambulatory Diastolic Blood Pressure Awake Index
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Systolic Blood Pressure Asleep Mean
timeFrame: Baseline
measure: Change in Ambulatory Systolic Blood Pressure Asleep Mean
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Diastolic Blood Pressure Asleep Mean
timeFrame: Baseline
measure: Change in Ambulatory Diastolic Blood Pressure Asleep Mean
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Systolic Blood Pressure Asleep Load
timeFrame: Baseline
measure: Change in Ambulatory Systolic Blood Pressure Asleep Load
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Diastolic Blood Pressure Asleep Load
timeFrame: Baseline
measure: Change in Ambulatory Diastolic Blood Pressure Asleep Load
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Systolic Blood Pressure Asleep Index
timeFrame: Baseline
measure: Change in Ambulatory Systolic Blood Pressure Asleep Index
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Diastolic Blood Pressure Asleep Index
timeFrame: Baseline
measure: Change in Ambulatory Diastolic Blood Pressure Asleep Index
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Systolic Blood Pressure Nocturnal Dipping
timeFrame: Baseline
measure: Change in Ambulatory Systolic Blood Pressure Nocturnal Dipping
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Diastolic Blood Pressure Nocturnal Dipping
timeFrame: Baseline
measure: Change in Ambulatory Diastolic Blood Pressure Nocturnal Dipping
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Inadequate Nocturnal Dipping
timeFrame: Baseline
measure: Change in Ambulatory Inadequate Nocturnal Dipping
timeFrame: Baseline through 2 years
measure: Baseline Ambulatory Hypertension
timeFrame: Baseline
measure: Change in Ambulatory Hypertension
timeFrame: Baseline through 2 years
measure: Baseline Relative Left Ventricular Wall Thickness
timeFrame: Baseline
measure: Change in Relative Left Ventricular Wall Thickness
timeFrame: Baseline through 2 years
measure: Baseline Elevated Relative Left Ventricular Wall Thickness
timeFrame: Baseline
measure: Change in Elevated Relative Left Ventricular Wall Thickness
timeFrame: Baseline through 2 years
measure: Baseline Left Ventricular Geometry Classification
timeFrame: Baseline
measure: Change in Left Ventricular Geometry Classification
timeFrame: Baseline through 2 years
measure: Baseline Left Ventricular Systolic Function
timeFrame: Baseline
measure: Change in Left Ventricular Systolic Function
timeFrame: Baseline through 2 years
measure: Baseline Left Ventricular Diastolic Function
timeFrame: Baseline
measure: Change in Left Ventricular Diastolic Function
timeFrame: Baseline through 2 years
measure: Baseline Left Atrial Size
timeFrame: Baseline
measure: Change in Left Atrial Size
timeFrame: Baseline through 2 years
measure: Baseline Left Atrial Enlargement
timeFrame: Baseline
measure: Change in Left Atrial Enlargement
timeFrame: Baseline through 2 years
measure: Baseline Urine Protein/Creatinine Ratio
timeFrame: Baseline
measure: Change in Urine Protein/Creatinine Ratio
timeFrame: Baseline through 2 years
measure: Baseline Proteinuria
timeFrame: Baseline
measure: Change in Proteinuria
timeFrame: Baseline through 2 years
measure: Baseline Serum Cystatin C Level
timeFrame: Baseline
measure: Change in Serum Cystatin C Level
timeFrame: Baseline through 2 years
measure: Baseline Elevated Urine Sodium Concentration
timeFrame: Baseline
measure: Change in Elevated Urine Sodium Concentration
timeFrame: Baseline through 2 years
measure: Baseline Elevated Urine Sodium/Potassium Ratio
timeFrame: Baseline
measure: Change in Elevated Urine Sodium/Potassium Ratio
timeFrame: Baseline through 2 years
measure: Low Estimated Glomerular Filtration Rate
timeFrame: Through study completion up to 2 years
measure: Baseline Urine Uric Acid/Creatinine Ratio
timeFrame: Baseline
measure: Change in Urine Uric Acid/Creatinine Ratio
timeFrame: Baseline through 2 years
measure: Baseline Urine Uric Acid Per Glomerular Filtration Rate
timeFrame: Baseline
measure: Change in Urine Uric Acid Per Glomerular Filtration Rate
timeFrame: Baseline through 2 years
measure: Baseline Fractional Excretion of Urine Uric Acid
timeFrame: Baseline
measure: Change in Fractional Excretion of Urine Uric Acid
timeFrame: Baseline through 2 years
measure: Baseline Serum Fibroblast Growth Factor 23 Level
timeFrame: Baseline
measure: Change in Serum Fibroblast Growth Factor 23 Level
timeFrame: Baseline through 2 years
measure: Baseline Urine Fibroblast Growth Factor 23 Level
timeFrame: Baseline
measure: Change in Urine Fibroblast Growth Factor 23 Level
timeFrame: Baseline through 2 years
measure: Baseline Obesity
timeFrame: Baseline
measure: Baseline Dietary Sodium Intake
timeFrame: Baseline
measure: Baseline Disordered Eating
timeFrame: Baseline
measure: Change in Disordered Eating
timeFrame: Baseline through 2 years
measure: Baseline Financial Stress
timeFrame: Baseline
measure: Change in Financial Stress
timeFrame: Baseline through 2 years
measure: Baseline Food Insecurity
timeFrame: Baseline
measure: Change in Food Insecurity
timeFrame: Baseline through 2 years
measure: Baseline Transportation Stress
timeFrame: Baseline
measure: Change in Transportation Stress
timeFrame: Baseline through 2 years
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest Health Sciences
name: Andrew M South, MD, MS
role: PRINCIPAL_INVESTIGATOR
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