Clinical trial NCT06595680: Development of an Innovative Hemodialysis Method to Improve Dialytic Clearance of Protein-bound Uremic Toxins
Official title: Development of an Innovative Hemodialysis Method to Improve Dialytic Clearance of Protein-bound Uremic Toxins
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
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
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: TREATMENT

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%).


Eligibility criteria: 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.

Primary outcomes:
measure: Dialytic clearance of p-CS
timeFrame: until 240 minutes after haemodialysis session
Secondary outcomes:
measure: Reduction fraction (RF) of p-CS
timeFrame: At 240 minutes after haemodialysis session
measure: Dialytic clearance of Indoxyl sulfate
timeFrame: until 240 minutes after haemodialysis session
measure: Reduction fraction (RF) of Indoxyl sulfate
timeFrame: At 240 minutes after haemodialysis session
measure: Dialytic clearance of hippuric acid
timeFrame: until 240 minutes after haemodialysis session
measure: Reduction fraction (RF) of hippuric acid
timeFrame: At 240 minutes after haemodialysis session
measure: Dialytic clearance of p-cresyl glucuronide
timeFrame: until 240 minutes after haemodialysis session
measure: Reduction fraction (RF) of p-cresyl glucuronide
timeFrame: At 240 minutes after haemodialysis session
measure: Dialytic clearance of indol acetic acid
timeFrame: until 240 minutes after haemodialysis session
measure: Reduction fraction (RF) of indol acetic acid
timeFrame: At 240 minutes after haemodialysis session
measure: Dialytic clearance of uric acid
timeFrame: until 240 minutes after haemodialysis session
measure: Reduction fraction (RF) of uric acid
timeFrame: At 240 minutes after haemodialysis session
measure: Dialytic clearance of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid
timeFrame: until 240 minutes after haemodialysis session
measure: Reduction fraction (RF) of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid
timeFrame: At 240 minutes after haemodialysis session
measure: Tolerance of medialipide perfusion (%)
timeFrame: until 240 minutes after haemodialysis session
measure: Safety of medialipide perfusion
timeFrame: until 7 days after the last haemodialysis session
measure: octanoate blood concentration
timeFrame: until 240 minutes after haemodialysis session
measure: decanoate blood concentration
timeFrame: until 240 minutes after haemodialysis session
measure: clearance of octanoate
timeFrame: until 240 minutes after haemodialysis session
measure: clearance of decanoate
timeFrame: until 240 minutes after haemodialysis session
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hopital Edouard Herriot
Study officials:
References: