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NCT Number: NCT03310684

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

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.

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Key information

Conditions

Pediatric Disorder Body Weight Cardiomegaly Cardiovascular Diseases Essential Hypertension Heart Diseases Hypertension Hypertrophy Hypertrophy, Left Ventricular Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Pediatric Obesity Primary Hypertension Signs and Symptoms Vascular Diseases

Age range

5 year–17 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. Left ventricular hypertrophy

    Time frame: Yearly for 3 years

    Left ventricular hypertrophy according to elevated left ventricular mass index (>51 g/m^2.7 (>8 years of age, both sexes) or >115 g/body surface area (males) and >95 g/body surface area (females)) on serial echocardiogram.

Secondary outcomes

  1. Albuminuria

    Time frame: Yearly for 3 years

    Albumin-to-creatinine ratio >30 mg/g

  2. Ambulatory systolic blood pressure load

    Time frame: Yearly for 3 years

    Percent of 24-hour ambulatory systolic blood pressure above the 95th percentile (>25% abnormal)

  3. Ambulatory diastolic blood pressure load

    Time frame: Yearly for 3 years

    Percent of 24-hour ambulatory diastolic blood pressure above the 95th percentile (>25% abnormal)

  4. Ambulatory systolic blood pressure nocturnal dipping

    Time frame: Yearly for 3 years

    Percent of 24-hour ambulatory systolic blood pressure that drops below the mean blood pressure overnight

  5. Ambulatory diastolic blood pressure nocturnal dipping

    Time frame: Yearly for 3 years

    Percent of 24-hour ambulatory diastolic blood pressure that drops below the mean blood pressure overnight

  6. Clinic systolic blood pressure

    Time frame: Yearly for 3 years

    Auscultated systolic blood pressure (mmHg)

  7. Clinic diastolic blood pressure

    Time frame: Yearly for 3 years

    Auscultated diastolic blood pressure (mmHg)

  8. Nonalcoholic fatty liver disease

    Time frame: Yearly for 3 years

    Fat infiltration (yes or no) as measured on liver ultrasound with elastography in subjects with overweight/obesity (BMI >=85th percentile)

  9. Continuous systolic blood pressure

    Time frame: Yearly for 3 years

    Systolic blood pressure measured continuously for 10 minutes (mmHg)

  10. Continuous diastolic blood pressure

    Time frame: Yearly for 3 years

    Diastolic blood pressure measured continuously for 10 minutes (mmHg)

Sponsors and collaborators

Lead sponsor

Wake Forest University Health Sciences

Other

Registry information

Official study title

The Role of the Renin-Angiotensin System in Pediatric Primary Hypertension (PHRAS)

Acronym: PHRAS

Important dates

Study start
2018
Primary completion
2023
Study completion
2023
First posted
Oct 16, 2017
Registry last updated
Feb 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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