Salt; ExcessEarly Phase 1PEPC3NCT04026776
Uric Acid, Klotho and Salt Sensitivity in Young Adults Born Preterm
A Early Phase 1 study testing Allopurinol and Dietary Intervention in people with Salt; Excess and Blood Pressure Disorders, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 to 33 yearsHealthy volunteers can take part
- Conditions the study is for
- Salt; Excess, Blood Pressure Disorders
- What is being tested?
- Allopurinol and Dietary Intervention
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 154 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Sep 2020to 1 Aug 2026
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 33 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Singleton birth
- Born at less than 34 weeks gestational age (preterm cohort)
- Born at greater than 36 weeks gestational age (term cohort)
Who cannot join
- Twin birth
- Congenital anomalies or genetic syndromes
- Currently pregnant or breast feeding
- Subject-reported history of hypertension
- Current use of antihypertensive medications
- Active cancer
Show all 9Show fewer
- Chronic kidney disease
- Heart failure
- Liver failure
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
The purpose of this research is to learn about how salt in the diet influences blood pressure in young adults who were born prematurely.
Read the 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.
- Conditions
- Salt; Excess, Blood Pressure Disorders
- Being tested
- Allopurinol, Dietary Intervention
- Keywords
- Uric Acid sensitivity, Salt sensitivity, Blood Pressure Influences
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AllopurinolDrug
Also called Zyloprim
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.
Dietary InterventionOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Preterm Group | Experimental | 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 Receives: Drug: Allopurinol; Other: Dietary Intervention |
| Term-born control group | Active comparator | Subjects with birth weight ≥2500 g will receive a dietary intervention (high/low salt diet) Receives: Other: Dietary Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion 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).
Measured: 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).
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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
Measured: First 3 study visits
Serum uric acid at baseline
Serum uric acid concentration at baseline
Measured: 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
Measured: 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
Measured: Day 42 to 56
Pulse wave velocity at baseline
Carotid femoral pulse wave velocity will be measured at baseline with the SphygmoCor XCEL device
Measured: Day 0
Augmentation index at baseline
Augmentation index will be measured at baseline with the SphygmoCor XCEL device
Measured: 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
Measured: 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
Measured: Day 0
Angiotensin-(1-7) at baseline
Plasma angiotensin-(1-7) concentration and urine angiotensin-(1-7)/creatinine at baseline
Measured: Day 0
Angiotensin II at baseline
Plasma angiotensin II concentration and urine angiotensin II/creatinine at baseline
Measured: Day 0
Klotho at baseline
Plasma klotho concentration and urine klotho/creatinine at baseline.
Measured: Day 0
Creatinine at baseline
Serum creatinine concentration at baseline
Measured: Day 0
Cystatin C at baseline
Serum cystatin C concentration at baseline
Measured: 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
Measured: Day 0
Secondary outcomes (67)
Ambulatory systolic blood pressure 24-hour mean at baseline
Average systolic blood pressure over 24 hours, measured with ambulatory blood pressure monitors
Measured: Day 0
Ambulatory diastolic blood pressure 24-hour mean at baseline
Average diastolic blood pressure over 24 hours, measured with ambulatory blood pressure monitors
Measured: Day 0
Ambulatory mean arterial pressure 24-hour mean at baseline
Average mean arterial pressure over 24 hours, measured with ambulatory blood pressure monitors
Measured: Day 0
Ambulatory systolic blood pressure awake mean at baseline
Average systolic blood pressure while awake, measured with ambulatory blood pressure monitors
Measured: Day 0
Ambulatory diastolic blood pressure awake mean at baseline
Average diastolic blood pressure while awake, measured with ambulatory blood pressure monitors
Measured: Day 0
Ambulatory mean arterial pressure awake mean at baseline
Average mean arterial pressure while awake, measured with ambulatory blood pressure monitors
Measured: Day 0
Ambulatory systolic blood pressure asleep mean at baseline
Average systolic blood pressure while asleep, measured with ambulatory blood pressure monitors
Measured: Day 0
Ambulatory diastolic blood pressure asleep mean at baseline
Average diastolic blood pressure while asleep, measured with ambulatory blood pressure monitors
Measured: Day 0
Ambulatory mean arterial pressure asleep mean at baseline
Average mean arterial pressure while asleep, measured with ambulatory blood pressure monitors
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Day 49 to 56
ACE2 at baseline
Serum ACE2 concentration and activity and urine ACE2/creatinine and activity at baseline
Measured: Day 0
ACE at baseline
Serum ACE concentration and activity and urine ACE/creatinine and activity at baseline
Measured: Day 0
FGF23 at baseline
Plasma fibroblast growth factor 23 (FGF23) concentration and urine FGF23/creatinine at baseline
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Day 49 to 56
Neprilysin level at baseline
Serum neprilysin concentration and activity and urine neprilysin/creatinine and activity at baseline
Measured: 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
Measured: 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
Measured: Day 49 to 56
Urine albumin at baseline
Urine albumin/creatinine at baseline on first-morning urine sample
Measured: Day 0
Proportion with albuminuria
Albuminuria at baseline, defined as urine albumin/creatinine >30 mg/g on first-morning urine sample
Measured: Day 0
Urine protein at baseline
Urine protein/creatinine at baseline on first-morning urine sample
Measured: Day 0
Proportion with proteinuria
Proteinuria at baseline, defined as urine protein/creatinine >0.2 mg/mg on first-morning urine sample
Measured: Day 0
Angiotensinogen at baseline
Serum angiotensinogen concentration and urine angiotensinogen/creatinine at baseline
Measured: 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
Measured: 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
Measured: Day 49 to 56
24-hour sodium excretion at baseline
Sodium excretion in the urine over 24 hours at baseline
Measured: Day 0
24-hour potassium excretion at baseline
Potassium excretion in the urine over 24 hours at baseline
Measured: Day 0
24-hour uric acid excretion at baseline
Uric acid excretion in the urine over 24 hours at baseline
Measured: Day 0
Pulse wave velocity (CF) at baseline
Carotid-femoral (CF) pulse wave velocity will be measured at baseline with the SphygmoCor XCEL device
Measured: 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
Measured: 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
Measured: Day 49 to 56
Angiotensin II:angiotensin-(1-7) at baseline
Plasma and urine angiotensin II:angiotensin-(1-7) at baseline
Measured: 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
Measured: 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
Measured: Day 49 to 56
ACE:ACE2 at baseline
Serum and urine ACE:ACE2 at baseline
Measured: 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
Measured: 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
Measured: Day 49 to 56
Body mass index at baseline
Body mass index at baseline
Measured: Day 0
Proportion with overweight/obesity
Overweight/obesity at baseline, defined as a body mass index >=25 kg/m2
Measured: Day 0
Proportion with obesity
Obesity at baseline, defined as a body mass index >=30 kg/m2
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2019
- Study start2 Sep 2020
- Primary completion1 Aug 2026
- Study completion1 Aug 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Salt; ExcessStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 154 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Hossam Shaltout, PhD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04026776
- Sponsor's protocol ID
- IRB00057527
- Other IDs
- 1R01HL146818-01A1
- Acronym
- PEPC3
- Status last verified
- Mar 2026
- First submitted
- 17 Jul 2019
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD that underlie the results reported in this record, after deidentification.
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Uric Acid, Klotho and Salt Sensitivity in Young Adults Born Preterm
- ClinicalTrials.gov ID
- NCT04026776
- Acronym / sponsor ID
- PEPC3 / IRB00057527
- Conditions
- Salt; Excess, Blood Pressure Disorders
- Keywords
- Uric Acid sensitivity, Salt sensitivity, Blood Pressure Influences
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 154 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 2 Sep 2020 (actual)
- Primary completion
- 1 Aug 2026 (actual)
- Study completion
- 1 Aug 2026 (actual)
- First posted
- 19 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Preterm Group | Experimental | Drug: Allopurinol, Other: Dietary InterventionSubjects 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 |
| Term-born control group | Active comparator | Other: Dietary InterventionSubjects with birth weight ≥2500 g will receive a dietary intervention (high/low salt diet) |
Who may qualify
- Ages
- 22 to 33 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Singleton birth
- Born at less than 34 weeks gestational age (preterm cohort)
- Born at greater than 36 weeks gestational age (term cohort)
Key exclusion criteria (9 listed)
- Twin birth
- Congenital anomalies or genetic syndromes
- Currently pregnant or breast feeding
- Subject-reported history of hypertension
- Current use of antihypertensive medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AllopurinolAlso: ZyloprimStudy 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. | Drug | Preterm Group |
| Dietary InterventionHigh-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. | Other | Preterm Group, Term-born control group |
Primary outcome
Proportion with salt sensitivity of blood pressure at baseline via ABPM
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Proportion with salt sensitivity of blood pressure after allopurinol via casual blood pressure
Time frame: 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 ABPM
Time frame: 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
Time frame: 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).
High blood pressure at baseline via casual blood pressure
Time frame: 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
Time frame: 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
Time frame: Day 0
Serum uric acid concentration at baseline
Change in serum uric acid with dietary Na+ intervention
Time frame: 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
Time frame: 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
Time frame: Day 0
Carotid femoral pulse wave velocity will be measured at baseline with the SphygmoCor XCEL device
Augmentation index at baseline
Time frame: Day 0
Augmentation index will be measured at baseline with the SphygmoCor XCEL device
Heart rate variability at baseline
Time frame: Day 0
Heart rate variability will be measured at baseline using continuous heart rate recording using the CNAP™ Monitor 500i
Baroreflex sensitivity at baseline
Time frame: 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
Time frame: Day 0
Plasma angiotensin-(1-7) concentration and urine angiotensin-(1-7)/creatinine at baseline
Angiotensin II at baseline
Time frame: Day 0
Plasma angiotensin II concentration and urine angiotensin II/creatinine at baseline
Klotho at baseline
Time frame: Day 0
Plasma klotho concentration and urine klotho/creatinine at baseline.
Creatinine at baseline
Time frame: Day 0
Serum creatinine concentration at baseline
Cystatin C at baseline
Time frame: Day 0
Serum cystatin C concentration at baseline
eGFR at baseline
Time frame: 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
67 secondary outcomes
Ambulatory systolic blood pressure 24-hour mean at baseline
Time frame: Day 0
Ambulatory diastolic blood pressure 24-hour mean at baseline
Time frame: Day 0
Ambulatory mean arterial pressure 24-hour mean at baseline
Time frame: Day 0
Ambulatory systolic blood pressure awake mean at baseline
Time frame: Day 0
Ambulatory diastolic blood pressure awake mean at baseline
Time frame: Day 0
Ambulatory mean arterial pressure awake mean at baseline
Time frame: Day 0
Ambulatory systolic blood pressure asleep mean at baseline
Time frame: Day 0
Ambulatory diastolic blood pressure asleep mean at baseline
Time frame: Day 0
Ambulatory mean arterial pressure asleep mean at baseline
Time frame: Day 0
Ambulatory systolic blood pressure 24-hour load at baseline
Time frame: Day 0
Ambulatory diastolic blood pressure 24-hour load at baseline
Time frame: Day 0
Ambulatory systolic blood pressure awake load at baseline
Time frame: Day 0
Ambulatory diastolic blood pressure awake load at baseline
Time frame: Day 0
Ambulatory systolic blood pressure asleep load at baseline
Time frame: Day 0
Ambulatory diastolic blood pressure asleep load at baseline
Time frame: Day 0
Ambulatory systolic blood pressure nocturnal dipping at baseline
Time frame: Day 0
Ambulatory diastolic blood pressure nocturnal dipping at baseline
Time frame: Day 0
Casual systolic blood pressure at baseline
Time frame: Day 0
Casual diastolic blood pressure at baseline
Time frame: Day 0
Change in pulse wave velocity with dietary Na+ intervention
Time frame: Day 7 to 14
Change in augmentation index with dietary Na+ intervention
Time frame: Day 7 to 14
Change in pulse wave velocity with dietary Na+ intervention while on allopurinol
Time frame: Day 49 to 56
Change in augmentation index with dietary Na+ intervention while on allopurinol
Time frame: Day 49 to 56
Change in heart rate variability with dietary Na+ intervention
Time frame: Day 7 to 14
Change in baroreflex sensitivity with dietary Na+ intervention
Time frame: Day 7 to 14
Change in heart rate variability with dietary Na+ intervention while on allopurinol
Time frame: Day 49 to 56
Change in baroreflex sensitivity with dietary Na+ intervention while on allopurinol
Time frame: Day 49 to 56
Change in angiotensin-(1-7) with dietary Na+ intervention
Time frame: Day 7 to 14
Change in angiotensin II with dietary Na+ intervention
Time frame: Day 7 to 14
Change in klotho with dietary Na+ intervention
Time frame: Day 7 to 14
Change in angiotensin-(1-7) with dietary Na+ intervention while on allopurinol
Time frame: Day 49 to 56
Change in angiotensin II with dietary Na+ intervention while on allopurinol
Time frame: Day 49 to 56
Change in klotho with dietary Na+ intervention while on allopurinol
Time frame: Day 49 to 56
ACE2 at baseline
Time frame: Day 0
ACE at baseline
Time frame: Day 0
FGF23 at baseline
Time frame: Day 0
Change in ACE2 with dietary Na+ intervention
Time frame: Day 7 to 14
Change in ACE2 with dietary Na+ intervention while on allopurinol
Time frame: Day 49 to 56
Change in ACE with dietary Na+ intervention
Time frame: Day 7 to 14
Change in ACE with dietary Na+ intervention while on allopurinol
Time frame: Day 49 to 56
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Individual participant dataSharing planned: Yes. IPD that underlie the results reported in this record, after deidentification.
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Ketone Ester and Salt (KEAS) in Young Adults
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hossam Shaltout, PhD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Allopurinol and Dietary Intervention in people with Salt; Excess and Blood Pressure Disorders, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion with salt sensitivity of blood pressure at baseline via ABPM (time frame: Day 7 to 14). The study lists 23 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.