Clinical trial NCT04026776: Uric Acid, Klotho and Salt Sensitivity in Young Adults Born Preterm
Official title: Uric Acid, Klotho and Salt Sensitivity in Young Adults Born Preterm
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Salt; Excess
Blood Pressure Disorders
Keywords: Uric Acid sensitivity
Salt sensitivity
Blood Pressure Influences
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2019-07-19
Enrollment: 120
Sex: ALL
Minimum age (years): 22
Maximum age (years): 33
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this research is to learn about how salt in the diet influences blood pressure in young adults who were born prematurely.

Detailed description: Premature birth is an emerging and important risk factor for hypertension and cardiovascular disease, as both preterm birth rates and infant survival increase worldwide. Hypertension and cardiovascular disease begin in early adulthood in individuals born prematurely, but the reasons especially in regard to the role of preterm birth are unknown. An improved understanding of why hypertension and cardiovascular disease occur in early adulthood in individuals born preterm will enable the development of prevention and treatment strategies to mitigate the burden of cardiovascular disease. Investigators propose to investigate these relationships mechanistically in a clinical trial of subjects born preterm to establish the SSBP (salt sensitivity of blood pressure) phenotype and study its relationship to CVD (cardiovascular disease) compared to a control group of healthy term- born peers. Investigators will then propose to determine if blocking UA (uric acid) formation improves SSBP and cardiovascular function in subjects born preterm.

Eligibility criteria: Inclusion Criteria:

* Singleton birth
* Born at less than 34 weeks gestational age (preterm cohort)
* Born at greater than 36 weeks gestational age (term cohort)

Exclusion Criteria:

* Twin birth
* Congenital anomalies or genetic syndromes
* Currently pregnant or breast feeding
* Subject-reported history of hypertension
* Current use of antihypertensive medications
* Active cancer
* Chronic kidney disease
* Heart failure
* Liver failure

Primary outcomes:
measure: Proportion with salt sensitivity of blood pressure at baseline via ABPM
timeFrame: Day 7 to 14
measure: Proportion with salt sensitivity of blood pressure after allopurinol via ABPM
timeFrame: Day 49 to 56
measure: Salt sensitivity index at baseline
timeFrame: Day 7 to 14
measure: Salt sensitivity index after allopurinol
timeFrame: Day 49 to 56
measure: Proportion with salt sensitivity of blood pressure at baseline via casual blood pressure
timeFrame: Day 7 to 14
measure: Proportion with salt sensitivity of blood pressure after allopurinol via casual blood pressure
timeFrame: Day 49 to 56
measure: High blood pressure at baseline via ABPM
timeFrame: Day 0
measure: Hypertension at baseline via ABPM
timeFrame: Day 7
measure: High blood pressure at baseline via casual blood pressure
timeFrame: First 3 study visits
measure: Hypertension at baseline via casual blood pressure
timeFrame: First 3 study visits
measure: Serum uric acid at baseline
timeFrame: Day 0
measure: Change in serum uric acid with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in serum uric acid with dietary Na+ intervention on allopurinol
timeFrame: Day 42 to 56
measure: Pulse wave velocity at baseline
timeFrame: Day 0
measure: Augmentation index at baseline
timeFrame: Day 0
measure: Heart rate variability at baseline
timeFrame: Day 0
measure: Baroreflex sensitivity at baseline
timeFrame: Day 0
measure: Angiotensin-(1-7) at baseline
timeFrame: Day 0
measure: Angiotensin II at baseline
timeFrame: Day 0
measure: Klotho at baseline
timeFrame: Day 0
measure: Creatinine at baseline
timeFrame: Day 0
measure: Cystatin C at baseline
timeFrame: Day 0
measure: eGFR at baseline
timeFrame: Day 0
Secondary outcomes:
measure: Ambulatory systolic blood pressure 24-hour mean at baseline
timeFrame: Day 0
measure: Ambulatory diastolic blood pressure 24-hour mean at baseline
timeFrame: Day 0
measure: Ambulatory mean arterial pressure 24-hour mean at baseline
timeFrame: Day 0
measure: Ambulatory systolic blood pressure awake mean at baseline
timeFrame: Day 0
measure: Ambulatory diastolic blood pressure awake mean at baseline
timeFrame: Day 0
measure: Ambulatory mean arterial pressure awake mean at baseline
timeFrame: Day 0
measure: Ambulatory systolic blood pressure asleep mean at baseline
timeFrame: Day 0
measure: Ambulatory diastolic blood pressure asleep mean at baseline
timeFrame: Day 0
measure: Ambulatory mean arterial pressure asleep mean at baseline
timeFrame: Day 0
measure: Ambulatory systolic blood pressure 24-hour load at baseline
timeFrame: Day 0
measure: Ambulatory diastolic blood pressure 24-hour load at baseline
timeFrame: Day 0
measure: Ambulatory systolic blood pressure awake load at baseline
timeFrame: Day 0
measure: Ambulatory diastolic blood pressure awake load at baseline
timeFrame: Day 0
measure: Ambulatory systolic blood pressure asleep load at baseline
timeFrame: Day 0
measure: Ambulatory diastolic blood pressure asleep load at baseline
timeFrame: Day 0
measure: Ambulatory systolic blood pressure nocturnal dipping at baseline
timeFrame: Day 0
measure: Ambulatory diastolic blood pressure nocturnal dipping at baseline
timeFrame: Day 0
measure: Casual systolic blood pressure at baseline
timeFrame: Day 0
measure: Casual diastolic blood pressure at baseline
timeFrame: Day 0
measure: Change in pulse wave velocity with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in augmentation index with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in pulse wave velocity with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Change in augmentation index with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Change in heart rate variability with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in baroreflex sensitivity with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in heart rate variability with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Change in baroreflex sensitivity with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Change in angiotensin-(1-7) with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in angiotensin II with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in klotho with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in angiotensin-(1-7) with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Change in angiotensin II with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Change in klotho with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: ACE2 at baseline
timeFrame: Day 0
measure: ACE at baseline
timeFrame: Day 0
measure: FGF23 at baseline
timeFrame: Day 0
measure: Change in ACE2 with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in ACE2 with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Change in ACE with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in ACE with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Change in FGF23 with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in FGF23 with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Neprilysin level at baseline
timeFrame: Day 0
measure: Change in neprilysin with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in neprilysin with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Urine albumin at baseline
timeFrame: Day 0
measure: Proportion with albuminuria
timeFrame: Day 0
measure: Urine protein at baseline
timeFrame: Day 0
measure: Proportion with proteinuria
timeFrame: Day 0
measure: Angiotensinogen at baseline
timeFrame: Day 0
measure: Change in angiotensinogen with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in angiotensinogen with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: 24-hour sodium excretion at baseline
timeFrame: Day 0
measure: 24-hour potassium excretion at baseline
timeFrame: Day 0
measure: 24-hour uric acid excretion at baseline
timeFrame: Day 0
measure: Pulse wave velocity (CF) at baseline
timeFrame: Day 0
measure: Change in pulse wave velocity (CF) with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in pulse wave velocity (CF) with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Angiotensin II:angiotensin-(1-7) at baseline
timeFrame: Day 0
measure: Change in angiotensin II:angiotensin-(1-7) with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in angiotensin II:angiotensin-(1-7) with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: ACE:ACE2 at baseline
timeFrame: Day 0
measure: Change in ACE:ACE2 with dietary Na+ intervention
timeFrame: Day 7 to 14
measure: Change in ACE:ACE2 with dietary Na+ intervention while on allopurinol
timeFrame: Day 49 to 56
measure: Body mass index at baseline
timeFrame: Day 0
measure: Proportion with overweight/obesity
timeFrame: Day 0
measure: Proportion with obesity
timeFrame: Day 0
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Hossam Shaltout, PhD
role: PRINCIPAL_INVESTIGATOR
References: