Phosphate in Blood Pressure Regulation

NCT ID: NCT02822131

Last Updated: 2016-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2016-06-30

Brief Summary

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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

low phosphate

low phosphate will be induced by low phosphate diet and additional treatment with oral phosphate binder sevelamer.

Group Type: OTHER

sevelamer, sodium bicarbonate, sodium chloride

Intervention Type: DRUG

high phosphate

high phosphate diet will be induced by oral supplementation with sodium phosphate.

Group Type: OTHER

sodium phosphate

Intervention Type: DIETARY_SUPPLEMENT

Interventions

sodium phosphate

Intervention Type: DIETARY_SUPPLEMENT

sevelamer, sodium bicarbonate, sodium chloride

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Nilufar Mohebbi

PD Dr. med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Hospital Zurich, Nephrology

Zurich, Canton of Zurich, Switzerland

Countries

Switzerland

Other Identifiers

Phos-RR

Identifier Type: -

Identifier Source: org_study_id