Renal Metabolism in Salt-sensitive Human Blood Pressure

Salt sensitive hypertension is a significant health problem worldwide and a primary modifiable risk factor for renal, cardiovascular, and cerebrovascular diseases. Yet, the underlying mechanisms remain poorly understood.

The proposed study determines how renal oxygenation and substrate metabolism differs between individuals with and without salt sensitivity, with the ultimate goal of identifying mechanisms, diagnostic criteria, and treatment strategies for salt sensitive hypertension.

Study Overview

• Status: Recruiting
• Conditions: Hypertension
• Intervention / Treatment: Other: Low sodium diet; Other: high sodium diet

Detailed Description

Seventy subjects will be enrolled and randomized to start either a low sodium diet (1200 mg/day) or high sodium diet (>4200 mg/day) for two weeks. After completion of two weeks, subjects will be switched to the 'other' diet for two weeks after a one-week wash-out. During the screening visit, subject's daily sodium intake will be assessed using multiple methods and further dietary information will be collected to prepare customized low sodium meals. During low sodium diet period, subjects will be supplied with food and will be asked to keep food logs. At the end of two-week period, the study activities described below will be carried out including BOLD MRI imaging along with imaging techniques to assess renal oxygenation levels and perfusion. During high sodium diet period, subjects will be either supplemented with sodium chloride tablets or high sodium foods to achieve a daily sodium intake above 4200 mg/day. If subjects already consume over 4200 mg/day of sodium, no changes will be made to their diet and assessment of oxygenation (BOLD MRI) and perfusion will take place after two weeks.

At the end of high sodium diet, 18 subjects will have renal vein sampling performed (this will be equally divided between salt-sensitive and salt-insensitive subjects and per subject preference as all may not want to have renal vein sampling). Subjects will be classified into salt sensitive or insensitive at the end of low sodium diet period based on BP response for further data analyses.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Srividya Kidambi, MD; Phone Number: 414-955-6724; Email: skidambi@mcw.edu
• Study Contact Backup: Name: Roland James, MA; Phone Number: 414-456-4992; Email: rjames@mcw.edu

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin /Froedtert Hospital
      • Contact: Srividya Kidambi, D/o; Phone Number: 414-955-6724; Email: skidambi@mcw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• English speaking subjects
• With a spectrum of BPs, ranging from those with Elevated BP through Stage 1 HTN, as defined by the 2017 ACC/AHA HTN guidelines

Exclusion Criteria:

• Non-English speakers
• BP ≤120/80 & ≥ 140/90 mmHg
• H/o diabetes, congestive heart failure, cirrhosis of the liver, hypokalemia & other
• electrolyte disturbances
• H/o kidney disease
• Use of glucocorticoids
• Pregnant or nursing mothers
• Presence of bleeding disorders
• Use of anti-platelet and anticoagulant agents such as clopidogrel, aspirin, dabigatran, rivaroxaban etc
• Daily sodium intake ≥ 6000 mg/day
• Presence of pacemaker or other metallic implants
• Allergy to iodinated contrast
• Allergy to shellfish
• Claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low sodium diet; -Subjects will be randomized to start a low sodium diet (1200 mg/day) for two weeks (this will be followed by a high sodium diet - crossover design)	Other: Low sodium diet; Subjects will be started on a low sodium (food will be provided) for two weeks.
Active Comparator: high sodium diet; -Subjects will be randomized to start a high sodium diet (4200 mg/day) for two weeks (this will be followed by a low sodium diet - crossover design)	Other: high sodium diet; Subjects will be started on high sodium diet (regular diet supplemented with salt tablets to reach a daily intake of > 4200 mg/Day) for two weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in renal regional tissue oxygenation in response to salt intake and salt sensitivity	70 subjects (~50% women, ~50% AA) will be recruited and salt sensitivity will be determined (defined as ≥8 mmHg decrease in systolic BP on a low Na+ diet). BOLD-MRI and MRI with arterial spin labeling (MRI-ASL) will be performed to assess renal regional tissue oxygenation and perfusion at baseline and after high and low Na+ diets.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in renal metabolites in response to a high sodium diet among individuals who are salt-sensitive versus insensitive	In a sub-sample (n=18), metabolomic analysis on peripheral blood and urine samples at baseline and at the end of both diet periods will be performed. These measures will include circulating and urine levels of ketones, acetate and lactate. In addition, peripheral arterial and renal vein samples will be obtained after high Na+ diet period for metabolomic analysis. The concurrent sampling of urine, arterial, and renal venous blood and metabolomics analyses will allow us to comprehensively assess renal uptake and release of metabolites in humans for the first time.	6 weeks

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Srividya Kidambi, MD, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Anticipated): January 30, 2030
• Study Completion (Anticipated): January 30, 2030

Study Registration Dates

• First Submitted: May 6, 2022
• First Submitted That Met QC Criteria: May 10, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 23, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: hypertension; salt; high blood pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: PRO00037003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No