Phosphate in Blood Pressure Regulation (Phos-RR)

The Effect of Dietary Phosphate Intake on Blood Pressure Regulation and Renal Sodium Chloride Excretion in Healthy Male Volunteers

High dietary phosphate intake in the general population is associated with a higher risk for developing kidney disease and cardiovascular disease with an increased overall mortality. Whereas the effects of high phosphate intake on general health become clearer, almost nothing is known about underlying mechanisms. More recently, the investigators and others found in animal models that FGF23 stimulates the renal NaCl cotransporter NCC, the target of thiazide diuretics, and that increased NCC activity may increase blood pressure. The investigators could also show that increasing dietary phosphate intake in mice, increases FGF23 and NCC activity within 3 days. Thus, the objective of this single-centre observational cross-over study including 20-45 year old healthy male probands is to elucidate the role of dietary phosphate on blood pressure regulation and renal handling of sodium chloride in healthy subjects. Further the impact of dietary phosphate intake on the regulation of phosphaturic hormones and other factors regulation blood pressure will be investigated. In addition, the investigators will examine whether phosphate intake modulates gut microbiome composition. The primary outcome in this study is the change in blood pressure in healthy subjects on low-phosphate diet compared to healthy subjects on high-phosphate diet. In addition, to assess changes in NCC activity as the main mechanism of phosphate-sensitive blood pressure regulation, renal sodium chloride excretion after administration of hydrochlorothiazide will be measured. The secondary outcomes of this study are: changes in renal phosphate, calcium and potassium excretion, changes in phosphate regulation hormones such as 25-OH-Vit. D, 1,25-(OH)2-Vit. D, PTH, FGF23, dopamine in plasma and urine, changes in plasma and urinary aldosterone levels, changes in sodium/chloride-cotransporter NCC and NaPi-IIa assessed from urinary exosomes, and changes in stool phosphate excretion and gut microbiome composition.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: sevelamer, sodium bicarbonate, sodium chloride; Dietary supplement: sodium phosphate

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • ZH
    • Zurich, ZH, Switzerland, 8091
      • University Hospital Zurich, Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 20-45 year old healthy male subjects

Exclusion Criteria:

• - Kidney disease (defined by eGFR < 90 ml/min or microalbuminuria (> 30mg/d))
• Diabetes mellitus
• Hypertension (RR > 140/85 mmHg)
• Hypotension (RR < 90/60 mmHg)
• any regular medication
• non-Western type diet e.g. vegetarian, vegan etc.
• History of kidney stones
• Allergy to sulphonamides or penicillins
• Hereditary fructose intolerance
• known hypersensitivity or allergy to class of drugs used in this study
• Glaucoma
• Vitamin D deficiency (< 20 ng/ml)
• Hyper- or Hypoparathyroidism
• Hypo- or hyperaldosteronism
• Participation in any other study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: low phosphate; low phosphate will be induced by low phosphate diet and additional treatment with oral phosphate binder sevelamer.	Drug: sevelamer, sodium bicarbonate, sodium chloride
Other: high phosphate; high phosphate diet will be induced by oral supplementation with sodium phosphate.	Dietary supplement: sodium phosphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in blood pressure	5 days
Change in renal sodium chloride excretion	5 days

Collaborators and Investigators

• Sponsor: University of Zurich

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: April 8, 2016
• First Submitted That Met QC Criteria: June 29, 2016
• First Posted (Estimate): July 4, 2016

Study Record Updates

• Last Update Posted (Estimate): July 4, 2016
• Last Update Submitted That Met QC Criteria: June 29, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Sevelamer
• Other Study ID Numbers: Phos-RR

Plan for Individual participant data (IPD)

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