Recruiting

Renin-Angiotensin System

Sponsor:

Wake Forest University Health Sciences

Code:

NCT04752293

Conditions

Hypertension

Left Ventricular Hypertrophy

Left Ventricular Dysfunction

Left Atrial Dilatation

Left Ventricular Diastolic Dysfunction

Eligibility Criteria

Sex: All

Age: 7 - 18

Healthy Volunteers: Accepted

Study Details

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.

Conditions

Hypertension

Left Ventricular Hypertrophy

Left Ventricular Dysfunction

Left Atrial Dilatation

Left Ventricular Diastolic Dysfunction

Study ID

NCT04752293

Start date

May 19, 2021

Status verified date

Dec, 2025

Completion date

Dec, 2026

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 7 - 18

Healthy Volunteers: Accepted

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

Study Design

Enrollment

125 participants

Anticipated

Interventions and Outcome Measures

Arms

Hypertension Cohort

Participants with newly diagnosed primary hypertension

Control Cohort

Healthy participants with normal blood pressure

Primary outcome measure

  • Baseline Urine Angiotensin-(1-7)/Creatinine Ratio [ Time Frame: Baseline ]
  • Change in Urine Angiotensin-(1-7)/Creatinine Ratio [ Time Frame: Baseline through 2 years ]
  • Baseline Urine Angiotensin II/Angiotensin-(1-7) Ratio [ Time Frame: Baseline ]
  • Change in Urine Angiotensin II/Angiotensin-(1-7) Ratio [ Time Frame: Baseline through 2 years ]
  • Baseline Plasma Angiotensin-(1-7) Level [ Time Frame: Baseline ]
  • Change in Plasma Angiotensin-(1-7) Level [ Time Frame: Baseline through 2 years ]
  • Baseline Plasma Angiotensin II/Angiotensin-(1-7) Ratio [ Time Frame: Baseline ]
  • Change in Plasma Angiotensin II/Angiotensin-(1-7) Ratio [ Time Frame: Baseline through 2 years ]
  • Baseline Serum Uric Acid Level [ Time Frame: Baseline ]
  • Change in Serum Uric Acid Level [ Time Frame: Baseline through 2 years ]
  • Baseline Plasma Klotho Level [ Time Frame: Baseline ]
  • Change in Plasma Klotho Level [ Time Frame: Baseline through 2 years ]
  • Baseline Urine Klotho/Creatinine Ratio [ Time Frame: Baseline ]
  • Change in Urine Klotho/Creatinine Ratio [ Time Frame: Baseline through 2 years ]
  • Baseline Manual Systolic Blood Pressure [ Time Frame: Baseline ]
  • Change in Manual Systolic Blood Pressure [ Time Frame: Baseline through 2 years ]
  • Baseline Manual Diastolic Blood Pressure [ Time Frame: Baseline ]
  • Change in Manual Diastolic Blood Pressure [ Time Frame: Baseline through 2 years ]
  • Baseline Manual Systolic Blood Pressure Z-score [ Time Frame: Baseline ]
  • Change in Manual Systolic Blood Pressure Z-score [ Time Frame: Baseline through 2 years ]
  • Baseline Manual Diastolic Blood Pressure Z-score [ Time Frame: Baseline ]
  • Change in Manual Diastolic Blood Pressure Z-score [ Time Frame: Baseline through 2 years ]
  • Baseline Ambulatory Systolic Blood Pressure 24-Hour Mean [ Time Frame: Baseline ]
  • Change in Ambulatory Systolic Blood Pressure 24-Hour Mean [ Time Frame: Baseline through 2 years ]
  • Baseline Ambulatory Diastolic Blood Pressure 24-Hour Mean [ Time Frame: Baseline ]
  • Change in Ambulatory Diastolic Blood Pressure 24-Hour Mean [ Time Frame: Baseline through 2 years ]
  • Baseline Left Ventricular Mass Height Index [ Time Frame: Baseline ]
  • Change in Left Ventricular Mass Height Index [ Time Frame: Baseline through 2 years ]
  • Baseline Left Ventricular Mass Body Surface Area Index [ Time Frame: Baseline ]
  • Change in Left Ventricular Mass Body Surface Area Index [ Time Frame: Baseline through 2 years ]
  • Baseline Left Ventricular Hypertrophy [ Time Frame: Baseline ]
  • Change in Left Ventricular Hypertrophy [ Time Frame: Baseline through 2 years ]
  • Baseline Urine Albumin/Creatinine Ratio [ Time Frame: Baseline ]
  • Change in Urine Albumin/Creatinine Ratio [ Time Frame: Baseline through 2 years ]
  • Baseline Albuminuria [ Time Frame: Baseline ]
  • Change in Albuminuria [ Time Frame: Baseline through 2 years ]
  • Baseline Serum Creatinine Level [ Time Frame: Baseline ]
  • Change in Serum Creatinine Level [ Time Frame: Baseline through 2 years ]
  • Baseline Estimated Glomerular Filtration Rate [ Time Frame: Baseline ]
  • Change in Estimated Glomerular Filtration Rate [ Time Frame: Baseline through 2 years ]
  • Baseline Urine Sodium Concentration [ Time Frame: Baseline ]
  • Change in Urine Sodium Concentration [ Time Frame: Baseline through 2 years ]
  • Baseline Urine Sodium/Potassium Ratio [ Time Frame: Baseline ]
  • Change in Urine Sodium/Potassium Ratio [ Time Frame: Baseline through 2 years ]
  • Baseline Plasma Renin Activity [ Time Frame: Baseline ]
  • Change in Plasma Renin Activity [ Time Frame: Baseline through 2 years ]
  • Baseline Serum Aldosterone Level [ Time Frame: Baseline ]
  • Change in Serum Aldosterone Level [ Time Frame: Baseline through 2 years ]

Central Contacts and Locations

Central contacts

Andrew M South, MD, MS

336.716.9640asouth@wakehealth.edu

Caroline B Lucas

336.713.8038cblucas@wakehealth.edu

Locations

Wake Forest Health Sciences

Recruiting

Winston-Salem, North Carolina, United States, 27157

Contacts

Andrew M South, MD, MS

336-716-9640asouth@wakehealth.edu

Caroline B Lucas

336.713.8038cblucas@wakehealth.edu

Principal Investigator:

Andrew M South, MD, MS

More Information

Sponsor

Wake Forest University Health Sciences

Last update posted

Dec 11, 2025

Last verified

Dec, 2025

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Wake Forest University Health Sciences on 2025-12-11.