Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03310684
Recruitment Status : Active, not recruiting
First Posted : October 16, 2017
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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.

Condition or disease
Pediatric Disorder Pediatric Obesity Primary Hypertension

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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 160 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Role of the Renin-Angiotensin System in Pediatric Primary Hypertension (PHRAS)
Actual Study Start Date : December 3, 2018
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Group/Cohort
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.
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).

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).



Primary Outcome Measures :
  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 Outcome Measures :
  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)


Biospecimen Retention:   Samples Without DNA
Blood and urine samples.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients of the Pediatric Nephrology Clinic and Pediatric Gastroenterology Clinic at Brenner Children's Hospital. Patients from a general pediatric clinic at Wake Forest Baptist Health.
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 >=13-/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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03310684


Locations
Layout table for location information
United States, North Carolina
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
Investigators
Layout table for investigator information
Principal Investigator: Andrew M South, MD MS Wake Forest University Health Sciences
  Study Documents (Full-Text)

Documents provided by Wake Forest University Health Sciences:
Study Protocol  [PDF] July 6, 2017
Informed Consent Form  [PDF] May 8, 2017

Publications:

Layout table for additonal information
Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03310684    
Other Study ID Numbers: IRB00041266
First Posted: October 16, 2017    Key Record Dates
Last Update Posted: September 16, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wake Forest University Health Sciences:
Renin-Angiotensin system
Hypertension
Obesity
Angiotensin-(1-7)
Angiotensin II
FGF23
Klotho
Uric acid
Left ventricular hypertrophy
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension
Essential Hypertension
Pediatric Obesity
Vascular Diseases
Cardiovascular Diseases
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight