PeTRA: Intestinal Phosphate Transporter Expression in CKD Patients

Sponsor

RWTH Aachen University (Other)

Overall Status

Terminated

CT.gov ID

NCT02539680

Collaborator

Chugai Pharmaceutical (Industry)

Enrollment

Location

Arms

Actual Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the present study is to study the expression of the various phosphate transporters in patients with normal or moderately impaired renal function or in patients on dialysis. In particular, the investigators want to clarify whether NaPi-IIb expression level decreases in CKD patients, which would render it a potentially inadequate pharmaceutical target in these patients.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases	Procedure: endoscopy	N/A

Detailed Description

Elevated serum phosphate is a potent predictor of death and cardiovascular events in patients with renal disease. Control of serum-phosphate to desired target ranges is insufficient in many patients with advanced chronic kidney disease (CKD), in particular dialysis patients despite dietary restrictions, optimized dialysis regimens and the use of phosphate binders. One reason why for example, phosphate binders are insufficient to control phosphate uptake in the intestine or why they even loose efficacy, is a compensatory upregulation of phosphate transporters in the gut wall.

Thus, several companies attempt to specifically interfere with intestinal phosphate transporters, in particular the NaPi-IIb transporter. However, recent Chugai data obtained in experimental CKD challenge the assumption that NaPi-IIb is the major therapeutic target in this situation. In addition to NaPi-IIb, PiT-1 and -2 also might contribute to phosphate transport.

In normal human intestinal mucosa the most prominent expression of all 3 transporters is observed in the duodenum, i.e. an area, which can easily be assessed by endoscopy.

During endoscopy a biopsy for research purposes will be obtained. Chugai will evaluate the expression level of NaPi-IIb, PiT-1, PiT-2, and villin1 at the mRNA and, if possible, the protein level.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Joint Study on Intestinal Phosphate-TRAnsporter Expression in CKD Patients

Actual Study Start Date :

Sep 1, 2015

Actual Primary Completion Date :

Oct 1, 2017

Actual Study Completion Date :

Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: normal renal function Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level.	Procedure: endoscopy duodenal biopsies
Experimental: CKD stage 3-5 (not on dialysis) Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level.	Procedure: endoscopy duodenal biopsies
Experimental: on dialysis Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level.	Procedure: endoscopy duodenal biopsies

Arm

Intervention/Treatment

Experimental: normal renal function

Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level.

Procedure: endoscopy

duodenal biopsies

Experimental: CKD stage 3-5 (not on dialysis)

Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level.

Procedure: endoscopy

duodenal biopsies

Experimental: on dialysis

Evaluation of the expression level of phosphate transporters at the mRNA and, if possible, on the protein level.

Procedure: endoscopy

duodenal biopsies

Outcome Measures

Primary Outcome Measures

Differences in the expression level of phosphate transporters in the duodenal of the populations [5 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Upper endoscopy for suspected or known esophageal or gastric pathology
Upper endoscopy for screening purposes
Written consent to take part in the study

Exclusion Criteria:

Food intake within 8 hours prior to the endoscopy
Major duodenal pathology, in particular duodenitis or duodenal ulcers or tumor
Contraindication to duodenal biopsy such as bleeding disorder
Treatment with medication known to regulate the expression or activity of intestinal phosphate transporters (e.g. nicotinamide)
Kidney transplant patients
Alcohol or drug abuse
Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study
Participation in a parallel clinical trial
Subjects who are in any state of dependency to the sponsor or the investigators
Employees of the sponsor or the investigators
Subjects who have been committed to an institution by legal or regulatory order

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Aachen	Aachen	NRW	Germany	52074

Sponsors and Collaborators

RWTH Aachen University
Chugai Pharmaceutical

Investigators

Principal Investigator: Georg Schlieper, PD Dr.med., Clinic for Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II)