Intracellular Phosphate Concentration Evolution During Hemodialysis by MR Spectroscopy (CIPHEMO)

February 23, 2018 updated by: Hospices Civils de Lyon

Intracellular Phosphate and Adenosine Triphosphate (ATP) Concentration Evolution by Magnetic Resonance (MR) Spectroscopy in Patients During Hemodialysis

End-stage renal disease is associated with hyperphosphatemia due to a decrease of renal phosphate excretion. This hyperphosphatemia is associated with an increase of cardiovascular risk and mortality. Thus, three therapeutic options have been developed: dietary restriction, administration of phosphate binders and phosphorus clearance by hemodialysis (HD).

During a standard HD session, around 600 to 700mg phosphate is removed from the plasma, whereas it contains only 90 mg inorganic phosphate (Pi); 85% of phosphate is stored in bones and teeth in hydroxyapatite form, 14% is stored in the intracellular space (90% organic phosphate and 10% Pi), and 1% remains in the extracellular space.

Currently, the source of Pi cleared during HD remains to be determined. Phosphorus (31P) magnetic resonance spectroscopy allows reliable, dynamic and non-invasive measurements of phosphate intracellular concentration. The investigator's team recently published data obtained in anephric pigs, suggesting that phosphate intracellular concentration increases during a HD session. In parallel, we showed that ATP intracellular concentration decreased. These results suggest that the source of Pi cleared during HD could be located inside the cell.

In this study, investigators will measure intracellular phosphate and ATP concentrations and intracellular potential of hydrogen (pH) evolution during hemodialysis in 12 patients suffering from end-stage renal disease by MR spectroscopy.

If these results were confirmed in humans, it could explain, at least in part, HD intolerance in some patients and would lead to modify therapeutic approaches of hyperphosphatemia, for example, by modifying HD sessions time.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lyon, France, 69003
        • Service de Néphrologie Pavillon P, Hôpital E. Herriot

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient suffering from end-stage renal disease, treated by chronic hemodialysis since at less 6 months
  • Phosphatemia (at the start of the session) ≥ 1,5 mmol/L and ≤ 3 mmol/L
  • written consent signed

Exclusion Criteria:

  • Major subject protected by law
  • Prisoners or subjects who are involuntarily incarcerated
  • Denutrition (weight loss ≥ 5 kg in one months/10 kg in 6 months, Body Mass Index (BMI) ≤ 21 kg/m2, albuminemia ≤ 35 g/L)
  • Obesity (BMI ≥ 30 kg/m2)
  • Phosphatemia at the start of the dialysis < 1,5 mmol/L or > 3 mmol/L
  • Secondary hyperparathyroidism with parathormone (PTH) ≥ 1000 pg/mL
  • Adynamic osteopathy (PTH ≤ 50 pg/mL)
  • Hypoparathyroidism with a history of parathyroidectomy
  • Hemoglobin ≤ 100 g/L
  • Contraindication to heparin
  • Temporary vascular access
  • Contraindication to resonance magnetic spectroscopy (pacemaker or insulin pump, metallic valvular prosthesis, valvular prosthesis not compatible with resonance magnetic spectroscopy, dental appliance, intracerebral clip, claustrophobic subject).
  • Simultaneous participation to another research protocol
  • Patient not affiliated to a social security system

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Patients suffering from ESRD treated by chronic hemodialysis
Patients aged from 18 to 80 years old, suffering from ESRD, treated by chronic hemodialysis since at least 6 months and whose phosphatemia at the beginning of HD sessions ranged from 1.5 to 3 mmol/L. Phosphorus (31P) magnetic resonance spectroscopy will be performed in these patients during hemodialysis in order to measure intracellular phosphate and ATP concentrations and intracellular pH evolution during hemodialysis.
Device: Phosphorus (31P) magnetic resonance spectroscopy
Phosphorus MR spectroscopy realized using a 3-Tesla MR imaging system. A twenty-cm circular surface coil will be set to the 31P resonance frequency and placed over the leg muscle region to obtain spectroscopy acquisitions. 31P MR spectra will be acquired before, during (every 160 seconds), and 30 minutes after dialysis. 31P MR system data will be analyzed using jMRUI Software. Five different peaks will be analyzed: inorganic phosphate, phosphocreatine, α-, β-, and γ-ATP.
Other: Hemodialysis
Hemodialysis realized using a 5008 generator, a portable plant, a FX80 Dialyzer, a dialyzing solution with a standard electrolytes composition. The dialysis generator will be placed outside of the MRI examination room. The dialysis lines will pass through a wave guide to connect patients positioned on the bed of the MRI. A suitably trained nurse will proceed to the cannulation of the fistula, the connection of the catheter, and the monitoring of the clinical tolerance of the session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in phosphate intracellular concentration
Time Frame: Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
Measurement of phosphate intracellular concentration evolution during a 4 hours hemodialysis (HD) session using phosphorus magnetic resonance spectroscopy.
Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in ATP intracellular concentration
Time Frame: Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
Measurement of ATP intracellular concentration evolution during a 4 hours HD session using phosphorus magnetic resonance spectroscopy.
Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
Change in intracellular pH
Time Frame: Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
Measurement of intracellular pH evolution during a 4 hours HD session using phosphorus magnetic resonance spectroscopy. Intracellular pH will be calculated using the Henderson-Hasselbach formula: Ph = 6.75 + log (δ-3.27)/(5.69-δ), with δ being the difference (in parts per million) between inorganic phosphate (Pi) and phosphocreatine (PCr) resonance frequencies.
Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
Change in phosphatemia
Time Frame: At start of HD, every 15 minutes during first hour of HD, then every hour during HD, at the end of HD and 30 minutes after HD
Measurement of intracellular pH evolution during a 4 hours HD session using phosphorus magnetic resonance spectroscopy. Intracellular pH will be calculated using the Henderson-Hasselbach formula: Ph = 6.75 + log (δ-3.27)/(5.69-δ), with δ being the difference (in parts per million) between Pi (inorganic phosphate) and PCr (phosphocreatine) resonance frequencies.
At start of HD, every 15 minutes during first hour of HD, then every hour during HD, at the end of HD and 30 minutes after HD
Calcium balance
Time Frame: At the end of a 4 hours HD session
Calcium balance will be measured using the formula: (Cae - Cab)(Ve - UF)+(Cae * UF), where Cae is the calcium in the effluent, Cab is the calcium in the dialysis solution, Ve is the volume of effluent, and UF is the ultrafiltration.
At the end of a 4 hours HD session

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 14, 2017

Primary Completion (ACTUAL)

July 29, 2017

Study Completion (ACTUAL)

July 29, 2017

Study Registration Dates

First Submitted

April 11, 2017

First Submitted That Met QC Criteria

April 18, 2017

First Posted (ACTUAL)

April 19, 2017

Study Record Updates

Last Update Posted (ACTUAL)

February 26, 2018

Last Update Submitted That Met QC Criteria

February 23, 2018

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL17_0047

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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