Uric Acid, Klotho and Salt Sensitivity in Young Adults Born Preterm

NCT04026776 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: IRB000575271R01HL146818-01A1
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Salt; Excess; Blood Pressure Disorders

Keywords

Uric Acid sensitivity; Salt sensitivity; Blood Pressure Influences

Outcome Measures

Primary Outcomes (23)

• 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).

  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).

  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.

  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

  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.

  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.

  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).

  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).

  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.

  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

  First 3 study visits

• Serum uric acid at baseline

  Serum uric acid concentration at baseline

  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

  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

  Day 42 to 56

• Pulse wave velocity at baseline

  Carotid femoral pulse wave velocity will be measured at baseline with the SphygmoCor XCEL device

  Day 0

• Augmentation index at baseline

  Augmentation index will be measured at baseline with the SphygmoCor XCEL device

  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

  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

  Day 0

• Angiotensin-(1-7) at baseline

  Plasma angiotensin-(1-7) concentration and urine angiotensin-(1-7)/creatinine at baseline

  Day 0

• Angiotensin II at baseline

  Plasma angiotensin II concentration and urine angiotensin II/creatinine at baseline

  Day 0

• Klotho at baseline

  Plasma klotho concentration and urine klotho/creatinine at baseline.

  Day 0

• Creatinine at baseline

  Serum creatinine concentration at baseline

  Day 0

• Cystatin C at baseline

  Serum cystatin C concentration at baseline

  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

  Day 0

Secondary Outcomes (67)

• 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

Study Arms (2)

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

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)

Other: Dietary Intervention

Interventions

Allopurinol DRUG

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.

Also known as: Zyloprim

Preterm Group

Dietary Intervention OTHER

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.

Preterm Group; Term-born control group

Eligibility Criteria

• Age: 22 Years - 33 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Wake Forest University Health Sciences: lead

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

MeSH Terms

Interventions

Allopurinol; Diet Therapy

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nutrition Therapy; Therapeutics

Study Officials

• Hossam Shaltout, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hossam Shaltout, PhD

CONTACT

336-716-1251; hshaltou@wakehealth.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 19, 2019
• Study Start: September 2, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 5 years following publication.
• Access Criteria: Proposals should be directed to hshaltou@wakehealth.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years.

Locations

US (1)