NCT02822131

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for not_applicable hypertension

Timeline
Completed

Started Jan 2016

Shorter than P25 for not_applicable hypertension

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2016

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

April 8, 2016

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
1 month until next milestone

First Posted

Study publicly available on registry

July 4, 2016

Completed
Last Updated

July 4, 2016

Status Verified

June 1, 2016

Enrollment Period

5 months

First QC Date

April 8, 2016

Last Update Submit

June 29, 2016

Conditions

Hypertension

Outcome Measures

Primary Outcomes (2)

  • Change in blood pressure

    5 days

  • Change in renal sodium chloride excretion

    5 days

Study Arms (2)

low phosphate

OTHER

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

Drug: sevelamer, sodium bicarbonate, sodium chloride

high phosphate

OTHER

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

Dietary Supplement: sodium phosphate

Interventions

sodium phosphateDIETARY_SUPPLEMENT
high phosphate
sevelamer, sodium bicarbonate, sodium chlorideDRUG
low phosphate

Eligibility Criteria

Age20 Years - 45 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • year old healthy male subjects

You may not qualify if:

  • \- 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Zurich, Nephrology

Zurich, Canton of Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Hypertension

Interventions

sodium phosphateSevelamerSodium BicarbonateSodium Chloride

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

PolyaminesAminesOrganic ChemicalsBicarbonatesCarbonatesCarbonic AcidCarbon Compounds, InorganicInorganic ChemicalsSodium CompoundsChloridesHydrochloric AcidChlorine Compounds

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
PD Dr. med.

Study Record Dates

First Submitted

April 8, 2016

First Posted

July 4, 2016

Study Start

January 1, 2016

Primary Completion

June 1, 2016

Study Completion

June 1, 2016

Last Updated

July 4, 2016

Record last verified: 2016-06

Data Sharing

IPD Sharing
Will not share

Locations

CH(1)