Pediatric Primary Hypertension and the Renin-Angiotensin System (PHRAS)

NCT ID: NCT03310684

Last Updated: 2025-02-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 35 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-12-03
• Study Completion Date: 2023-04-26

Brief Summary

Pediatric primary hypertension is increasingly common, occurring in 5-10% of normal-weight children and up to 25% of children with obesity. It is a risk factor for adult cardiovascular and renal disease. But even during childhood, hypertension is associated with significant morbidity, including cognitive impairment and organ damage. In the heart and kidneys, this organ damage is characterized by thickened heart muscle (left ventricular hypertrophy) and spillage of protein in the urine (albuminuria). Obese children are also at risk for fatty liver disease. However, the cause of pediatric primary hypertension, the role of obesity, and the mechanisms behind heart and kidney injury are poorly understood. Due to these limitations, there are no first-line medications, and treatment is often inadequate. An altered renin-angiotensin system may cause primary hypertension and related organ damage. Evidence suggests uric acid, FGF23, klotho, and obesity play a role in renin-angiotensin system-mediated injury. An improved comprehension of the pathophysiology of pediatric primary hypertension could enhance clinical care by targeting treatment to the cause of disease and informing novel measurement of organ damage.

Detailed Description

This proposal is to begin to elucidate the origins of pediatric primary hypertension and determine how it causes cardiac and renal disease. The primary hypothesis is than an altered renin-angiotensin system leads to the development of pediatric primary hypertension-related organ damage in the heart and kidney, specifically left ventricular hypertrophy and albuminuria. It is postulated that relative increase in angiotensin (Ang) ll tone compared to Ang-(1-7) tone in the circulation and the kidney (measured in the plasma and urine, respectively) leads to disease. The secondary hypotheses are that abnormalities in renin-angiotensin system tone are related to higher uric acid and FGF23, lower klotho, and, with concurrent obesity, contribute to nonalcoholic fatty liver disease. The investigators will recruit 100 subjects aged 5-17 years who are referred for a new diagnosis of pediatric primary hypertension to the Pediatric Nephrology clinic at Brenner Children's Hospital, 50 normotensive subjects with obesity recruited from the Brenner Families-in-Training program, and 10 healthy normotensive from a general pediatrics clinic in the Wake Forest Baptist Health System.

Conditions

Pediatric Disorder; Pediatric Obesity; Primary Hypertension

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Hypertensive

Clinical data will be collected from the electronic medical record, including height, weight, age, sex, parent-reported race, and past medical and family histories. Antihypertensive medication type and dosage will be recorded. Blood and urine samples will be collected at baseline and yearly for three years. All subjects will receive baseline and yearly echocardiograms. Subjects with overweight/obesity (BMI \>=85th percentile for age and sex) will receive baseline and yearly ultrasounds of the liver to evaluate for hepatic fat infiltration. Auscultated, continuous and ambulatory blood pressure will be measured at baseline and yearly.

No interventions assigned to this group

Normotensive with Obesity

Clinical data will be collected from the electronic medical record, including height, weight, age, sex, parent-reported race, and past medical and family histories. Subjects will receive a baseline ultrasound of the liver to evaluate hepatic fat infiltration as per standard of care.

Blood and urine will be collected at baseline to measure liver function (AST, ALT) and uric acid, angiotensin ll, and angiotensin-(1-7).

No interventions assigned to this group

Healthy Normotensive

Clinical data will be collected from the electronic medical record, including height, weight, age, sex, parent-reported race, and past medical and family histories. Subjects will have baseline echocardiograms. Blood pressure will be measured at baseline and at one year. Continuous blood pressure and ambulatory blood pressure monitoring will be assessed at baseline. Blood and urine samples will be used to measure uric acid, FGF23, klotho, and albumin, as well as the predictors angiotensin ll and angiotensin-(1-7).

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Hypertension cohort: 5 to 17 years old with a new diagnosis of pediatric primary hypertension (systolic or diastolic blood pressure >=95th percentile for age/sex/height or >=130/80 mmHg.
• Normotensive controls with obesity: 5 to 17 years old with normal systolic and diastolic blood pressure (<90th percentile for age/sex/height or <120/80 mmHg) and BMI >=85th percentile for age/sex.
• Normotensive controls: 5 to 17 years old with normal systolic and diastolic blood pressure (<90th percentile for age/sex/height or <120/80 mmHg).

Exclusion Criteria

• Secondary hypertension
• Confounding medical condition (e.g. diabetes mellitus, chronic kidney disease, heart disease, vascular disease, inflammatory or rheumatologic disease)
• Non-English and non-Spanish speaking
• Inability to complete assessments

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew M South, MD MS

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Countries

United States

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Provided Documents

Document Type: Study Protocol

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Document Type: Informed Consent Form

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Other Identifiers

IRB00041266

Identifier Type: -

Identifier Source: org_study_id