The purpose of this research is to learn about how salt in the diet influences blood pressure in young adults who were born prematurely.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
120
Study Part 2- Preterm group only: After Visit 5 preterm born participants will start allopurinol 200 mg daily PO for 6 weeks. The 1 week high and low salt diets and assessments will be repeated while on allopurinol.
High-Na+ (250 mmol/d) and low-Na+ (50 mmol/d) standard isocaloric K+ diets (75 mmol/1000 kcal/d) for 1 week each as 3 meals and 1 snack a day provided by the Clinical Research Unit Metabolic Kitchen. Part 2 preterm only- the diets will be repeated while the participant is taking allopurinol.
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
RECRUITINGProportion with salt sensitivity of blood pressure at baseline via ABPM
Defined as a ≥8 mmHg decrease in mean arterial blood pressure when moving from the high-Na+ to the low-Na+ phase, as measured on 24-hour ambulatory blood pressure monitoring (ABPM).
Time frame: Day 7 to 14
Proportion with salt sensitivity of blood pressure after allopurinol via ABPM
A ≥8 mmHg decrease in mean arterial blood pressure when moving from the high-Na+ to the low-Na+ phase while taking allopurinol, as measured on 24-hour ambulatory blood pressure monitoring (ABPM).
Time frame: Day 49 to 56
Salt sensitivity index at baseline
The ratio between the change in 24-hour mean arterial pressure, as measured on 24-hour ambulatory blood pressure monitoring, and the change in 24-hour urine Na+ concentration when moving from the high-Na+ phase to the low-Na+ phase.
Time frame: Day 7 to 14
Salt sensitivity index after allopurinol
The ratio between the change in 24-hour mean arterial pressure, as measured on 24-hour ambulatory blood pressure monitoring, and the change in 24-hour urine Na+ concentration when moving from the high-Na+ phase to the low-Na+ phase while taking allopurinol
Time frame: Day 49 to 56
Proportion with salt sensitivity of blood pressure at baseline via casual blood pressure
A \>=5 mmHg decrease in mean arterial blood pressure measured in clinic when moving from the high-Na+ phase to the low-Na+ phase. Casual blood pressure measured 3 consecutive times via auscultation with the average of the 3 mean arterial blood pressure measurements recorded.
Time frame: Day 7 to 14
Proportion with salt sensitivity of blood pressure after allopurinol via casual blood pressure
A \>=5 mmHg decrease in mean arterial blood pressure measured in clinic when moving from the high-Na+ phase to the low-Na+ phase while taking allopurinol. Casual blood pressure measured 3 consecutive times via auscultation with the average of the 3 mean arterial blood pressure measurements recorded.
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Time frame: Day 49 to 56
High blood pressure at baseline via ABPM
Proportion with 24-hour mean systolic or diastolic blood pressure ≥115/75 mmHg, awake mean systolic or diastolic blood pressure ≥120/80 mmHg, or asleep mean systolic or diastolic blood pressure ≥100/65 mmHg, measured with ambulatory blood pressure monitoring (ABPM).
Time frame: Day 0
Hypertension at baseline via ABPM
Proportion with 24-hour mean systolic or diastolic blood pressure ≥125/75 mmHg, awake mean systolic or diastolic blood pressure ≥130/80 mmHg, or asleep mean systolic or diastolic blood pressure ≥110/65 mmHg, measured with ambulatory blood pressure monitoring (ABPM).
Time frame: Day 7
High blood pressure at baseline via casual blood pressure
Proportion with mean systolic or diastolic blood pressure ≥120/80 mmHg, measured via 3 consecutive auscultated measurements (averaged) at each of 3 separate study visits.
Time frame: First 3 study visits
Hypertension at baseline via casual blood pressure
Proportion with mean systolic or diastolic blood pressure ≥130/80 mmHg, measured via 3 consecutive auscultated measurements (averaged) at each of 3 separate study visits
Time frame: First 3 study visits
Serum uric acid at baseline
Serum uric acid concentration at baseline
Time frame: Day 0
Change in serum uric acid with dietary Na+ intervention
The change in serum uric acid levels when moving from high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in serum uric acid with dietary Na+ intervention on allopurinol
The change in serum uric acid levels when moving from high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 42 to 56
Pulse wave velocity at baseline
Carotid femoral pulse wave velocity will be measured at baseline with the SphygmoCor XCEL device
Time frame: Day 0
Augmentation index at baseline
Augmentation index will be measured at baseline with the SphygmoCor XCEL device
Time frame: Day 0
Heart rate variability at baseline
Heart rate variability will be measured at baseline using continuous heart rate recording using the CNAP™ Monitor 500i
Time frame: Day 0
Baroreflex sensitivity at baseline
Baroreflex sensitivity will be measured at baseline using continuous blood pressure and heart rate using the CNAP™ Monitor 500i
Time frame: Day 0
Angiotensin-(1-7) at baseline
Plasma angiotensin-(1-7) concentration and urine angiotensin-(1-7)/creatinine at baseline
Time frame: Day 0
Angiotensin II at baseline
Plasma angiotensin II concentration and urine angiotensin II/creatinine at baseline
Time frame: Day 0
Klotho at baseline
Plasma klotho concentration and urine klotho/creatinine at baseline.
Time frame: Day 0
Creatinine at baseline
Serum creatinine concentration at baseline
Time frame: Day 0
Cystatin C at baseline
Serum cystatin C concentration at baseline
Time frame: Day 0
eGFR at baseline
Estimated glomerular filtration rate (eGFR) at baseline.We will calculate the eGFR by the CKD-EPI Creatinine-Cystatin C 2012 equation and by 24 hour creatinine
Time frame: Day 0
Ambulatory systolic blood pressure 24-hour mean at baseline
Average systolic blood pressure over 24 hours, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory diastolic blood pressure 24-hour mean at baseline
Average diastolic blood pressure over 24 hours, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory mean arterial pressure 24-hour mean at baseline
Average mean arterial pressure over 24 hours, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory systolic blood pressure awake mean at baseline
Average systolic blood pressure while awake, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory diastolic blood pressure awake mean at baseline
Average diastolic blood pressure while awake, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory mean arterial pressure awake mean at baseline
Average mean arterial pressure while awake, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory systolic blood pressure asleep mean at baseline
Average systolic blood pressure while asleep, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory diastolic blood pressure asleep mean at baseline
Average diastolic blood pressure while asleep, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory mean arterial pressure asleep mean at baseline
Average mean arterial pressure while asleep, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory systolic blood pressure 24-hour load at baseline
Proportion of mean 24-hour systolic blood pressures ≥125 mmHg, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory diastolic blood pressure 24-hour load at baseline
Proportion of mean 24-hour diastolic blood pressures ≥75 mmHg, measured with ambulatory blood pressure monitors.
Time frame: Day 0
Ambulatory systolic blood pressure awake load at baseline
Proportion of mean awake systolic blood pressures ≥130 mmHg, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory diastolic blood pressure awake load at baseline
Proportion of mean awake diastolic blood pressures ≥80 mmHg, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory systolic blood pressure asleep load at baseline
Proportion of mean asleep systolic blood pressures ≥110 mmHg, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory diastolic blood pressure asleep load at baseline
Proportion of mean asleep diastolic blood pressures ≥65 mmHg, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory systolic blood pressure nocturnal dipping at baseline
Percent change in mean awake to mean asleep systolic blood pressure, measured with ambulatory blood pressure monitors
Time frame: Day 0
Ambulatory diastolic blood pressure nocturnal dipping at baseline
Percent change in mean awake to mean asleep diastolic blood pressure, measured with ambulatory blood pressure monitors
Time frame: Day 0
Casual systolic blood pressure at baseline
Measured 3 consecutive times via auscultation with the average of the 3 systolic blood pressure measurements recorded
Time frame: Day 0
Casual diastolic blood pressure at baseline
Measured 3 consecutive times via auscultation with the average of the 3 diastolic blood pressure measurements recorded
Time frame: Day 0
Change in pulse wave velocity with dietary Na+ intervention
The change in carotid femoral pulse wave velocity will be measured with the SphygmoCor XCEL device when moving from high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in augmentation index with dietary Na+ intervention
The change in augmentation index will be measured with the SphygmoCor XCEL device when moving from high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in pulse wave velocity with dietary Na+ intervention while on allopurinol
The change in carotid femoral pulse wave velocity will be measured with the SphygmoCor XCEL device when moving from high-Na+ phase to the low-Na+ phase while on allopurinol.
Time frame: Day 49 to 56
Change in augmentation index with dietary Na+ intervention while on allopurinol
The change in augmentation index will be measured with the SphygmoCor XCEL device when moving from high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Change in heart rate variability with dietary Na+ intervention
The change in heart rate variability will be measured using the Continuous noninvasive arterial pressure (CNAP™) Monitor 500i when moving from high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in baroreflex sensitivity with dietary Na+ intervention
The change in baroreflex sensitivity will be measured using the CNAP™ Monitor 500i when moving from high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in heart rate variability with dietary Na+ intervention while on allopurinol
The change in heart rate variability will be measured using the CNAP™ Monitor 500i when moving from high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Change in baroreflex sensitivity with dietary Na+ intervention while on allopurinol
The change in baroreflex sensitivity will be measured using the CNAP™ Monitor 500i when moving from high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Change in angiotensin-(1-7) with dietary Na+ intervention
The change in plasma angiotensin-(1-7) concentration and urine angiotensin-(1-7)/creatinine when moving from the high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in angiotensin II with dietary Na+ intervention
The change in plasma angiotensin II concentration and urine angiotensin II/creatinine when moving from the high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in klotho with dietary Na+ intervention
The change in plasma klotho concentration and urine klotho/creatinine when moving from the high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in angiotensin-(1-7) with dietary Na+ intervention while on allopurinol
The change in plasma angiotensin-(1-7) concentration and urine angiotensin-(1-7)/creatinine when moving from the high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Change in angiotensin II with dietary Na+ intervention while on allopurinol
The change in plasma angiotensin II concentration and urine angiotensin II/creatinine when moving from the high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Change in klotho with dietary Na+ intervention while on allopurinol
The change in plasma klotho concentration and urine klotho/creatinine when moving from the high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
ACE2 at baseline
Serum ACE2 concentration and activity and urine ACE2/creatinine and activity at baseline
Time frame: Day 0
ACE at baseline
Serum ACE concentration and activity and urine ACE/creatinine and activity at baseline
Time frame: Day 0
FGF23 at baseline
Plasma fibroblast growth factor 23 (FGF23) concentration and urine FGF23/creatinine at baseline
Time frame: Day 0
Change in ACE2 with dietary Na+ intervention
The change in serum ACE2 concentration and activity and urine ACE2/creatinine and activity when moving from the high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in ACE2 with dietary Na+ intervention while on allopurinol
The change in serum ACE2 concentration and activity and urine ACE2/creatinine and activity when moving from the high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Change in ACE with dietary Na+ intervention
The change in serum ACE concentration and activity and urine ACE2/creatinine and activity when moving from the high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in ACE with dietary Na+ intervention while on allopurinol
The change in serum ACE concentration and activity and urine ACE2/creatinine and activity when moving from the high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Change in FGF23 with dietary Na+ intervention
The change in serum fibroblast growth factor 23 (FGF23) concentration and urine FGF23/creatinine when moving from the high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in FGF23 with dietary Na+ intervention while on allopurinol
The change in serum fibroblast growth factor 23 (FGF23) concentration and urine FGF23/creatinine when moving from the high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Neprilysin level at baseline
Serum neprilysin concentration and activity and urine neprilysin/creatinine and activity at baseline
Time frame: Day 0
Change in neprilysin with dietary Na+ intervention
The change in serum neprilysin concentration and activity and urine neprilysin/creatinine and activity when moving from the high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in neprilysin with dietary Na+ intervention while on allopurinol
The change in serum neprilysin concentration and activity and urine neprilysin/creatinine and activity when moving from the high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Urine albumin at baseline
Urine albumin/creatinine at baseline on first-morning urine sample
Time frame: Day 0
Proportion with albuminuria
Albuminuria at baseline, defined as urine albumin/creatinine \>30 mg/g on first-morning urine sample
Time frame: Day 0
Urine protein at baseline
Urine protein/creatinine at baseline on first-morning urine sample
Time frame: Day 0
Proportion with proteinuria
Proteinuria at baseline, defined as urine protein/creatinine \>0.2 mg/mg on first-morning urine sample
Time frame: Day 0
Angiotensinogen at baseline
Serum angiotensinogen concentration and urine angiotensinogen/creatinine at baseline
Time frame: Day 0
Change in angiotensinogen with dietary Na+ intervention
The change in serum angiotensinogen concentration and urine angiotensinogen/creatinine when moving from the high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in angiotensinogen with dietary Na+ intervention while on allopurinol
The change in serum angiotensinogen concentration and urine angiotensinogen/creatinine when moving from the high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
24-hour sodium excretion at baseline
Sodium excretion in the urine over 24 hours at baseline
Time frame: Day 0
24-hour potassium excretion at baseline
Potassium excretion in the urine over 24 hours at baseline
Time frame: Day 0
24-hour uric acid excretion at baseline
Uric acid excretion in the urine over 24 hours at baseline
Time frame: Day 0
Pulse wave velocity (CF) at baseline
Carotid-femoral (CF) pulse wave velocity will be measured at baseline with the SphygmoCor XCEL device
Time frame: Day 0
Change in pulse wave velocity (CF) with dietary Na+ intervention
The change in carotid-femoral (CF) pulse wave velocity will be measured with the SphygmoCor XCEL device when moving from high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in pulse wave velocity (CF) with dietary Na+ intervention while on allopurinol
The change in carotid-femoral (CF) pulse wave velocity will be measured with the SphygmoCor XCEL device when moving from high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Angiotensin II:angiotensin-(1-7) at baseline
Plasma and urine angiotensin II:angiotensin-(1-7) at baseline
Time frame: Day 0
Change in angiotensin II:angiotensin-(1-7) with dietary Na+ intervention
The change in plasma angiotensin II:angiotensin-(1-7) when moving from the high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in angiotensin II:angiotensin-(1-7) with dietary Na+ intervention while on allopurinol
The change in plasma angiotensin II:angiotensin-(1-7) when moving from the high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
ACE:ACE2 at baseline
Serum and urine ACE:ACE2 at baseline
Time frame: Day 0
Change in ACE:ACE2 with dietary Na+ intervention
The change in serum and urine ACE:ACE2 when moving from the high-Na+ phase to the low-Na+ phase
Time frame: Day 7 to 14
Change in ACE:ACE2 with dietary Na+ intervention while on allopurinol
The change in serum and urine ACE:ACE2 when moving from the high-Na+ phase to the low-Na+ phase while on allopurinol
Time frame: Day 49 to 56
Body mass index at baseline
Body mass index at baseline
Time frame: Day 0
Proportion with overweight/obesity
Overweight/obesity at baseline, defined as a body mass index \>=25 kg/m2
Time frame: Day 0
Proportion with obesity
Obesity at baseline, defined as a body mass index \>=30 kg/m2
Time frame: Day 0