Development of an Innovative Hemodialysis Method to Improve Dialytic Clearance of Protein-bound Uremic Toxins

NCT06595680 | Not Yet Recruiting Phase 2

• 2 other identifiers: 69HCL23_00312023-510406-41-00
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Current hemodialysis techniques fail to efficiently remove protein-bound uremic toxins (such as p-cresyl sulfate (p-CS) or indoxyl sulfate (IS)) due to their strong binding to serum albumin. The accumulation of these toxins in end-stage renal failure patients on hemodialysis is strongly suspected to contribute to the significant morbidity and mortality observed in this population. Pre-clinical studies conducted previously showed that medium-chain fatty acids (such as sodium octanoate and decanoate), which are natural ligands of albumin, can effectively displace the binding of uremic toxins on serum albumin and thus promote their elimination during a hemodialysis session. Medialipide® 20% (Braun) is an emulsion of medium chain triglycerides (MCT) (6 to 12 carbons) used in parenteral nutrition. Medialipide® constitutes a relevant clinical formulation for the administration of octanoate and decanoate because it contains 94% of sodium octanoate and decanoate. In this study, a proof of concept intervention will be carried out to study the effect on the clearance uremic toxins clearance of the perfusion of Medialipide® emulsion (as a sodium octanoate and decanoate donor) in patients during their hemodialysis session compared to a control situation Sodium chloride (NaCl) 0,9%).

Conditions

End Stage Renal Disease; Chronic Hemolysis

Keywords

End stage renal disease; Hemodialysis; Protein Bound Uremic Toxins; p-Cresyl Sulfate; Indoxyl Sulfate; Medium Chain fatty acids; Medium chain triglycerides; Octanoate; Decanoate; Medialipide

Outcome Measures

Primary Outcomes (1)

• Dialytic clearance of p-CS

  Dialysis clearance of p-CS (millilitre/minute) is defined as follows: Clearance = Qd X (C dialysate/C arterial) with Qd corresponding to the dialysate flow rate, C dialysate the concentration of p-CS in the dialysate, C arterial the concentration of p-CS in the blood sampled at the arterial port of the dialyser.

  until 240 minutes after haemodialysis session

Secondary Outcomes (19)

• Reduction fraction (RF) of p-CS

  At 240 minutes after haemodialysis session

• Dialytic clearance of Indoxyl sulfate

  until 240 minutes after haemodialysis session

• Reduction fraction (RF) of Indoxyl sulfate

  At 240 minutes after haemodialysis session

• Dialytic clearance of hippuric acid

  until 240 minutes after haemodialysis session

• Reduction fraction (RF) of hippuric acid

  At 240 minutes after haemodialysis session

Study Arms (2)

Medialipide 20% - NaCl 0,9%

EXPERIMENTAL

Group 1 will receive during the first interventional hemodialysis session a perfusion of Medialipide 20% perfused at a rate of 0,11 gram/kilogram/hour (g/kg/h) during 4 hours. One week late, they will receive during the second interventional hemodialysis session a perfusion of NaCl 0,9% with a volume corresponding to the one of Medialipide also during 4 hours.

Drug: Medialipide 20% perfusion; Drug: NaCl 0,9%; Biological: Blood sample

NaCl 0,9% - Medialipide 20%

EXPERIMENTAL

Group 2 will receive during the first interventional hemodialysis session a perfusion of NaCl 0,9% with a volume corresponding to the one of Medialipide during 4 hours. One week late, they will receive during the second interventional hemodialysis session a perfusion of Medialipide 20% perfused at a rate of 0,11 gram/kilogram/hour (g/kg/h) also during 4 hours.

Drug: Medialipide 20% perfusion; Drug: NaCl 0,9%; Biological: Blood sample

Interventions

Medialipide 20% perfusion DRUG

Each patient will receive during a 4 hours hemodialysis session a perfusion of Medialipide 20% at a rate of 0,11 g/kg/h. Medialipide will be perfused using the venous line connected to the hemodialysis machine.

Medialipide 20% - NaCl 0,9%; NaCl 0,9% - Medialipide 20%

NaCl 0,9% DRUG

Each patient will receive during a 4 hours hemodialysis session a perfusion of NACL 0,9% with a volume corresponding to the one of Medialipide 20%. NaCl 0,9% will be perfused using the venous line connected to the hemodialysis machine.

Medialipide 20% - NaCl 0,9%; NaCl 0,9% - Medialipide 20%

Blood sample BIOLOGICAL

Serial biological sampling for the measurement of different blood concentrations : electrolytes, serum protein , albumin, renal function (urea, creatinine), hemoglobin, hematocrit, liver test, lipid test, ketone bodies, 6 uremic toxins (including IS and p-CS), sodium octanoate and decanoate.

Medialipide 20% - NaCl 0,9%; NaCl 0,9% - Medialipide 20%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• On haemodialysis at a frequency of 3 sessions of 4 hours per week, for at least 3 months.
• Patient affiliated to a social security scheme
• Free, informed and written consent signed by the patient

You may not qualify if:

• Residual diuresis \> 100 mL per day
• Pregnant or breast-feeding
• Uncontrolled hypertension \> 180/115 millimetre of mercury (mmHg)
• Perdialytic hypotension requiring vascular filling \> 100 mL during the last 3 sessions
• Patients already on parenteral nutrition
• Patients with allergy to heparin or requiring haemodialysis without anticoagulant (recent haemorrhage)
• Criteria relating to products/procedures: Patient with
• an allergy to egg, soya or peanut proteins or to one of the active ingredients or one of the excipients (glycerol, egg phospholipids for injection, a-tocopherol, sodium oleate (to adjust the pH), water for injection) of Médialipide
• Severe hyperlipidaemia or severe lipid metabolism disorder characterised by hypertriglyceridaemia \> 3 mmol/l
• Sepsis \< 1 month
• Severe liver failure or cholestasis
• Known severe coagulopathy
• Acute thrombo-embolic events
• Fat embolism
• Aggravating bleeding diathesis,

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hopital Edouard Herriot

Lyon, 69003, France

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Perfusion; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative

Central Study Contacts

Fitsum GUEBRE EGZIABHER, PU,PH

CONTACT

0472110260; fitsum.guebre-egziabher@chu-lyon.fr

Laure-Anne RAILLON

CONTACT

0633345131; laure-anne.raillon@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each patient will sequentially receive during two 4 hours hemodialysis session separated by one week a perfusion of Medialipide and a perfusion of NaCl 0,9%. The order of intervention will be determined by randomization.

Study Record Dates

• First Submitted: September 6, 2024
• First Posted: September 19, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 22, 2027
• Study Completion (Estimated): January 22, 2027
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

FR (1)