Uric Acid, Klotho and Salt Sensitivity in Young Adults Born Preterm
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Proportion with salt sensitivity of blood pressure at baseline via ABPM
研究概览
简要总结
The purpose of this research is to learn about how salt in the diet influences blood pressure in young adults who were born prematurely.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 22 Years 至 33 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Singleton birth
- •Born at less than 34 weeks gestational age (preterm cohort)
- •Born at greater than 36 weeks gestational age (term cohort)
排除标准
- •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
研究组 & 干预措施
Preterm Group
Subjects with very low birth weight (<37 completed weeks' gestation and birth weight <1500 g) will receive a dietary intervention (high/low salt diet) and FDA approved drug, Allopurinol
干预措施: Allopurinol (Drug)
Preterm Group
Subjects with very low birth weight (<37 completed weeks' gestation and birth weight <1500 g) will receive a dietary intervention (high/low salt diet) and FDA approved drug, Allopurinol
干预措施: Dietary Intervention (Other)
Term-born control group
Subjects with birth weight ≥2500 g will receive a dietary intervention (high/low salt diet)
干预措施: Dietary Intervention (Other)
结局指标
主要结局
Proportion with salt sensitivity of blood pressure at baseline via ABPM
时间窗: Day 7 to 14
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).
Proportion with salt sensitivity of blood pressure after allopurinol via ABPM
时间窗: Day 49 to 56
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).
Salt sensitivity index at baseline
时间窗: Day 7 to 14
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.
Salt sensitivity index after allopurinol
时间窗: Day 49 to 56
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
Proportion with salt sensitivity of blood pressure at baseline via casual blood pressure
时间窗: Day 7 to 14
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.
High blood pressure at baseline via ABPM
时间窗: Day 0
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).
Hypertension at baseline via ABPM
时间窗: Day 7
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).
Proportion with salt sensitivity of blood pressure after allopurinol via casual blood pressure
时间窗: Day 49 to 56
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.
High blood pressure at baseline via casual blood pressure
时间窗: First 3 study visits
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.
Hypertension at baseline via casual blood pressure
时间窗: First 3 study visits
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
Serum uric acid at baseline
时间窗: Day 0
Serum uric acid concentration at baseline
Change in serum uric acid with dietary Na+ intervention
时间窗: Day 7 to 14
The change in serum uric acid levels when moving from high-Na+ phase to the low-Na+ phase
Change in serum uric acid with dietary Na+ intervention on allopurinol
时间窗: Day 42 to 56
The change in serum uric acid levels when moving from high-Na+ phase to the low-Na+ phase while on allopurinol
Pulse wave velocity at baseline
时间窗: Day 0
Carotid femoral pulse wave velocity will be measured at baseline with the SphygmoCor XCEL device
Augmentation index at baseline
时间窗: Day 0
Augmentation index will be measured at baseline with the SphygmoCor XCEL device
Heart rate variability at baseline
时间窗: Day 0
Heart rate variability will be measured at baseline using continuous heart rate recording using the CNAP™ Monitor 500i
Baroreflex sensitivity at baseline
时间窗: Day 0
Baroreflex sensitivity will be measured at baseline using continuous blood pressure and heart rate using the CNAP™ Monitor 500i
Angiotensin-(1-7) at baseline
时间窗: Day 0
Plasma angiotensin-(1-7) concentration and urine angiotensin-(1-7)/creatinine at baseline
Angiotensin II at baseline
时间窗: Day 0
Plasma angiotensin II concentration and urine angiotensin II/creatinine at baseline
Klotho at baseline
时间窗: Day 0
Plasma klotho concentration and urine klotho/creatinine at baseline.
Creatinine at baseline
时间窗: Day 0
Serum creatinine concentration at baseline
Cystatin C at baseline
时间窗: Day 0
Serum cystatin C concentration at baseline
eGFR at baseline
时间窗: Day 0
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
次要结局
- Proportion with proteinuria(Day 0)
- Angiotensinogen at baseline(Day 0)
- Change in pulse wave velocity (CF) with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Angiotensin II:angiotensin-(1-7) at baseline(Day 0)
- Change in angiotensin II:angiotensin-(1-7) with dietary Na+ intervention(Day 7 to 14)
- Change in angiotensin II:angiotensin-(1-7) with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- ACE:ACE2 at baseline(Day 0)
- Change in ACE:ACE2 with dietary Na+ intervention(Day 7 to 14)
- Change in ACE:ACE2 with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Body mass index at baseline(Day 0)
- Proportion with overweight/obesity(Day 0)
- Proportion with obesity(Day 0)
- Ambulatory systolic blood pressure awake load at baseline(Day 0)
- Casual diastolic blood pressure at baseline(Day 0)
- Change in pulse wave velocity with dietary Na+ intervention(Day 7 to 14)
- Change in augmentation index with dietary Na+ intervention(Day 7 to 14)
- Ambulatory systolic blood pressure 24-hour mean at baseline(Day 0)
- Ambulatory diastolic blood pressure 24-hour mean at baseline(Day 0)
- Ambulatory mean arterial pressure 24-hour mean at baseline(Day 0)
- Ambulatory systolic blood pressure awake mean at baseline(Day 0)
- Ambulatory diastolic blood pressure awake mean at baseline(Day 0)
- Ambulatory mean arterial pressure awake mean at baseline(Day 0)
- Ambulatory systolic blood pressure asleep mean at baseline(Day 0)
- Ambulatory diastolic blood pressure asleep mean at baseline(Day 0)
- Ambulatory mean arterial pressure asleep mean at baseline(Day 0)
- Ambulatory systolic blood pressure 24-hour load at baseline(Day 0)
- Ambulatory diastolic blood pressure 24-hour load at baseline(Day 0)
- Ambulatory diastolic blood pressure awake load at baseline(Day 0)
- Ambulatory diastolic blood pressure nocturnal dipping at baseline(Day 0)
- Ambulatory systolic blood pressure asleep load at baseline(Day 0)
- Ambulatory systolic blood pressure nocturnal dipping at baseline(Day 0)
- Change in pulse wave velocity with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Change in angiotensin-(1-7) with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Change in angiotensin II with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- ACE2 at baseline(Day 0)
- Ambulatory diastolic blood pressure asleep load at baseline(Day 0)
- Casual systolic blood pressure at baseline(Day 0)
- Change in heart rate variability with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Change in klotho with dietary Na+ intervention(Day 7 to 14)
- Change in angiotensinogen with dietary Na+ intervention(Day 7 to 14)
- Change in angiotensinogen with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- 24-hour sodium excretion at baseline(Day 0)
- 24-hour potassium excretion at baseline(Day 0)
- 24-hour uric acid excretion at baseline(Day 0)
- Change in pulse wave velocity (CF) with dietary Na+ intervention(Day 7 to 14)
- Change in baroreflex sensitivity with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Change in angiotensin-(1-7) with dietary Na+ intervention(Day 7 to 14)
- Change in angiotensin II with dietary Na+ intervention(Day 7 to 14)
- Change in klotho with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Urine protein at baseline(Day 0)
- Pulse wave velocity (CF) at baseline(Day 0)
- Change in augmentation index with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- ACE at baseline(Day 0)
- FGF23 at baseline(Day 0)
- Change in ACE2 with dietary Na+ intervention(Day 7 to 14)
- Change in ACE2 with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Change in ACE with dietary Na+ intervention(Day 7 to 14)
- Change in ACE with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Change in FGF23 with dietary Na+ intervention(Day 7 to 14)
- Change in FGF23 with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Neprilysin level at baseline(Day 0)
- Change in neprilysin with dietary Na+ intervention while on allopurinol(Day 49 to 56)
- Change in heart rate variability with dietary Na+ intervention(Day 7 to 14)
- Change in baroreflex sensitivity with dietary Na+ intervention(Day 7 to 14)
- Change in neprilysin with dietary Na+ intervention(Day 7 to 14)
- Urine albumin at baseline(Day 0)
- Proportion with albuminuria(Day 0)