Renal Metabolism in Salt-sensitive Human Blood Pressure

• ClinicalTrials.gov Identifier: NCT05369416
• Recruitment Status: Recruiting
• First Posted: May 11, 2022
• Last Update Posted: May 25, 2022
• Sponsor: Medical College of Wisconsin
• Information provided by (Responsible Party): Srividya Kidambi, MD, Medical College of Wisconsin

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypertension	Other: Low sodium diet; Other: high sodium diet	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)

Masking Description

We are using a crossover design of low-sodium and high-sodium diets of 2 week duration each.

Both diets consecutively given to each subject recruited in the study.

• Primary Purpose: Basic Science
• Official Title: Renal Metabolism in Salt-sensitive Human Blood Pressure
• Actual Study Start Date: November 1, 2021
• Estimated Primary Completion Date: January 30, 2030
• Estimated Study Completion Date: January 30, 2030

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Changes in renal regional tissue oxygenation in response to salt intake and salt sensitivity [ Time Frame: 6 weeks ]
   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.

Secondary Outcome Measures :

1. Changes in renal metabolites in response to a high sodium diet among individuals who are salt-sensitive versus insensitive [ Time Frame: 6 weeks ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Srividya Kidambi, MD; 414-955-6724; skidambi@mcw.edu

Contact: Roland James, MA; 414-456-4992; rjames@mcw.edu

Locations

United States, Wisconsin

Medical College of Wisconsin /Froedtert Hospital; Recruiting

Milwaukee, Wisconsin, United States, 53226

Contact: Srividya Kidambi, D/o 414-955-6724 skidambi@mcw.edu

Sponsors and Collaborators

Medical College of Wisconsin

Investigators

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

More Information

• Responsible Party: Srividya Kidambi, MD, Associate Professor, Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT05369416
• Other Study ID Numbers: PRO00037003
• First Posted: May 11, 2022
• Last Update Posted: May 25, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Srividya Kidambi, MD, Medical College of Wisconsin:

hypertension; high blood pressure; salt

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases