Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT06595680

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

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%).

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hopital Edouard Herriot

Lyon, 69003, France

Location contact

Fitsum GUEBRE-EGZIABHER, PU,PH

CONTACT

[email protected]

0472110260 ext. +33

Fitsum GUEBRE-EGZIABHER, PU,PH

PRINCIPAL_INVESTIGATOR

Laure-Anne RAILLON

CONTACT

[email protected]

0633345131 ext. +33

Laure-Anne RAILLON

SUB_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥18 years
  • On haemodialysis at a frequency of 3 sessions of 4 hours per week, for at least 3 months.
  • For patients of childbearing age, effective contraception (sexual abstinence, hormonal contraception, intrauterine device or hormone-releasing system, cap, diaphragm or sponge with spermicide, condom) for the entire duration of treatment is required. A blood pregnancy test (beta-human chorionic gonadotropin (HCG)) will be carried out at inclusion.
  • Patient affiliated to a social security scheme
  • Free, informed and written consent signed by the patient

Exclusion criteria

  • 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 already on Vitamin K antagonists (VKA) (or prescribed less than one month before inclusion)
  • 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,
  • Uncompensated metabolic acidosis.
  • Unstable circulatory state threatening the vital prognosis (collapse and shock),
  • Unstable metabolic conditions (e.g. severe post-traumatic syndrome, coma of unknown origin),
  • Acute phase of myocardial infarction or stroke,
  • Uncorrected disturbances of fluid and electrolyte balance, such as hypokalaemia and hypotonic dehydration.
  • Decompensated heart failure,
  • Acute pulmonary oedema.
  • Subject participating in another interventional study involving a drug with an exclusion period still in progress at inclusion.

Treatment and study plan

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.

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.

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.

Primary outcomes

  1. Dialytic clearance of p-CS

    Time frame: until 240 minutes after haemodialysis session

    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.

Secondary outcomes

  1. Reduction fraction (RF) of p-CS

    Time frame: At 240 minutes after haemodialysis session

    Reduction fraction will be measured in percentage Reduction fraction will be compared between the medialipide perfusion situation and the NACL 0,9% perfusion situation.

    RF (%) = (Concentration of p-CS at T0 - Concentration of p-CS at T240)/Concentration of p-CS at T0

  2. Dialytic clearance of Indoxyl sulfate

    Time frame: until 240 minutes after haemodialysis session

    Dialysis clearance of Indoxyl sulfate (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 Indoxyl sulfate in the dialysate, C arterial the concentration of Indoxyl sulfate in the blood sampled at the arterial port of the dialyser.

  3. Reduction fraction (RF) of Indoxyl sulfate

    Time frame: At 240 minutes after haemodialysis session

    Reduction fraction will be measured in percentage Reduction fraction will be compared between the medialipide perfusion situation and the NACL 0,9% perfusion situation.

    RF (%) = (Concentration of Indoxyl sulfate at T0 - Concentration of Indoxyl sulfate at T240)/Concentration of Indoxyl sulfate at T0

  4. Dialytic clearance of hippuric acid

    Time frame: until 240 minutes after haemodialysis session

    Dialysis clearance of hippuric acid (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 hippuric acid in the dialysate, C arterial the concentration of hippuric acid in the blood sampled at the arterial port of the dialyser.

  5. Reduction fraction (RF) of hippuric acid

    Time frame: At 240 minutes after haemodialysis session

    Reduction fraction will be measured in percentage Reduction fraction will be compared between the medialipide perfusion situation and the NACL 0,9% perfusion situation.

    RF (%) = (Concentration of hippuric acid at T0 - Concentration of hippuric acid at T240)/Concentration of hippuric acid at T0

  6. Dialytic clearance of p-cresyl glucuronide

    Time frame: until 240 minutes after haemodialysis session

    Dialysis clearance of p-cresyl glucuronide (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-cresyl glucuronide in the dialysate, C arterial the concentration of p-cresyl glucuronide in the blood sampled at the arterial port of the dialyser.

  7. Reduction fraction (RF) of p-cresyl glucuronide

    Time frame: At 240 minutes after haemodialysis session

    Reduction fraction will be measured in percentage Reduction fraction will be compared between the medialipide perfusion situation and the NACL 0,9% perfusion situation.

    RF (%) = (Concentration of p-cresyl glucuronide at T0 - Concentration of p-cresyl glucuronide at T240)/Concentration of p-cresyl glucuronide at T0

  8. Dialytic clearance of indol acetic acid

    Time frame: until 240 minutes after haemodialysis session

    Dialysis clearance of indol acetic acid (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 indol acetic acid in the dialysate, C arterial the concentration of indol acetic acid in the blood sampled at the arterial port of the dialyser.

  9. Reduction fraction (RF) of indol acetic acid

    Time frame: At 240 minutes after haemodialysis session

    Reduction fraction will be measured in percentage Reduction fraction will be compared between the medialipide perfusion situation and the NACL 0,9% perfusion situation.

    RF (%) = (Concentration of indol acetic acid at T0 - Concentration of indol acetic acid at T240)/Concentration of indol acetic acid at T0

  10. Dialytic clearance of uric acid

    Time frame: until 240 minutes after haemodialysis session

    Dialysis clearance of indol acetic acid (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 uric acid in the dialysate, C arterial the concentration of uric acid in the blood sampled at the arterial port of the dialyser.

  11. Reduction fraction (RF) of uric acid

    Time frame: At 240 minutes after haemodialysis session

    Reduction fraction will be measured in percentage Reduction fraction will be compared between the medialipide perfusion situation and the NACL 0,9% perfusion situation.

    RF (%) = (Concentration of uric acid at T0 - Concentration of uric acid at T240)/Concentration of uric acid at T0

  12. Dialytic clearance of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid

    Time frame: until 240 minutes after haemodialysis session

    Dialysis clearance of indol acetic acid (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 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid in the dialysate, C arterial the concentration of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid in the blood sampled at the arterial port of the dialyser.

  13. Reduction fraction (RF) of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid

    Time frame: At 240 minutes after haemodialysis session

    Reduction fraction will be measured in percentage Reduction fraction will be compared between the medialipide perfusion situation and the NACL 0,9% perfusion situation.

    RF (%) = (Concentration of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid at T0 - Concentration of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid at T240)/Concentration of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid at T0

  14. Tolerance of medialipide perfusion (%)

    Time frame: until 240 minutes after haemodialysis session

    Percentage of patients with the occurrence of at least one symptom including: nausea, emesis, headaches during the hemodialysis session

  15. Safety of medialipide perfusion

    Time frame: until 7 days after the last haemodialysis session

    % of patients who presented one of the following event : hypertriglyceridemia > 4 gram/liter, alteration of liver test (cytolysis > 2 times the normal value, cholestasis > 2 times the normal value), or hemolysis.

  16. octanoate blood concentration

    Time frame: until 240 minutes after haemodialysis session

  17. decanoate blood concentration

    Time frame: until 240 minutes after haemodialysis session

  18. clearance of octanoate

    Time frame: until 240 minutes after haemodialysis session

    Dialysis clearance of Indoxyl sulfate (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 octanoate in the dialysate, C arterial the concentration of octanoate in the blood sampled at the arterial port of the dialyser.

  19. clearance of decanoate

    Time frame: until 240 minutes after haemodialysis session

    Dialysis clearance of Indoxyl sulfate (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 decanoate in the dialysate, C arterial the concentration of decanoate in the blood sampled at the arterial port of the dialyser.

Study contacts

Contact information is provided by the study sponsor or research team.

Fitsum GUEBRE EGZIABHER, PU,PH

CONTACT

[email protected]

0472110260 ext. +33

Laure-Anne RAILLON

CONTACT

[email protected]

0633345131 ext. +33

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Acronym: CLEARTOX

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Sep 19, 2024
Registry last updated
Sep 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.