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

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ClinicalTrials.gov Identifier: NCT03119818
Recruitment Status : Completed
First Posted : April 19, 2017
Last Update Posted : February 26, 2018
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Tracking Information
First Submitted Date  ICMJE April 11, 2017
First Posted Date  ICMJE April 19, 2017
Last Update Posted Date February 26, 2018
Actual Study Start Date  ICMJE June 14, 2017
Actual Primary Completion Date July 29, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intracellular Phosphate Concentration Evolution During Hemodialysis by MR Spectroscopy
Official Title  ICMJE Intracellular Phosphate and Adenosine Triphosphate (ATP) Concentration Evolution by Magnetic Resonance (MR) Spectroscopy in Patients During Hemodialysis
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE End-Stage Renal Disease (ESRD)
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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.
Interventions:
  • Device: Phosphorus (31P) magnetic resonance spectroscopy
  • Other: Hemodialysis
Publications * Chazot G, Lemoine S, Kocevar G, Kalbacher E, Sappey-Marinier D, Rouvière O, Juillard L. Intracellular Phosphate and ATP Depletion Measured by Magnetic Resonance Spectroscopy in Patients Receiving Maintenance Hemodialysis. J Am Soc Nephrol. 2021 Jan;32(1):229-237. doi: 10.1681/ASN.2020050716. Epub 2020 Oct 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 23, 2018)
11
Original Estimated Enrollment  ICMJE
 (submitted: April 18, 2017)
15
Actual Study Completion Date  ICMJE July 29, 2017
Actual Primary Completion Date July 29, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03119818
Other Study ID Numbers  ICMJE 69HCL17_0047
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hospices Civils de Lyon
Study Sponsor  ICMJE Hospices Civils de Lyon
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Laurent JUILLARD, MD, PhD Hospices Civils de Lyon
PRS Account Hospices Civils de Lyon
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP