Phos-RR: Phosphate in Blood Pressure Regulation

Sponsor

University of Zurich (Other)

Overall Status

Completed

CT.gov ID

NCT02822131

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Dietary Supplement: sodium phosphate Drug: sevelamer, sodium bicarbonate, sodium chloride	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Study Start Date :

Jan 1, 2016

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 1, 2016

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in blood pressure [5 days]
Change in renal sodium chloride excretion [5 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Zurich, Nephrology	Zurich	ZH	Switzerland	8091

Sponsors and Collaborators

University of Zurich

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Nilufar Mohebbi, PD Dr. med., University of Zurich

ClinicalTrials.gov Identifier:

NCT02822131

Other Study ID Numbers:

Phos-RR

First Posted:

Jul 4, 2016

Last Update Posted:

Jul 4, 2016

Last Verified:

Jun 1, 2016

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Hypertension

Sevelamer

Study Results

No Results Posted as of Jul 4, 2016