Evaluation of Interaction Between Immunosuppressive Drugs and Protein-bound Uremic Toxins in Renal Transplant Patients

Immunosuppression Clinical Trial

— DRUGTOX  

Official title:

Evaluation of Interaction Between Immunosuppressive Drugs and Protein-bound Uremic Toxins in Renal Transplant Patients

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04963673
• Other study ID #: PI2019_843_0060
• Status: Withdrawn
• Start date: July 6, 2021
• Est. completion date: September 12, 2023

Study information

• Verified date: September 2023
• Source: Centre Hospitalier Universitaire, Amiens
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The majority of studies conducted on uremic toxins involve patients before end stage renal failure or dialysis patients. Only a few studies have focused on transplant patients. In addition, the relationship between serum concentrations of uremic toxins and immunosuppressive drug concentrations has never been studied to date.

The investigator research hypothesis is that, due to the strong plasma protein binding of calcineurin inhibitors, an interaction with protein-bound uremic toxins could alter drug concentrations that explain difficulties in reaching therapeutic targets.

Description:

In France, the national prevalence of end-stage kidney disease (including dialysis and renal transplantation) is 1,232 per million inhabitants. As in all transplants, renal transplantation needs immunosuppressive therapy. This treatment may be difficult to adjust in some patients. However, achieving the therapeutic target is essential to have an efficiency synonymous with graft survival and better tolerance to the drug. The immunosuppressive class drug of interest in the present project is the class of calcineurin inhibitors (tacrolimus and ciclosporin) that are widely used in both initial and maintenance immunosuppression. These drugs have the pharmacological specificities to be highly bound to plasma proteins and requiring pharmacological therapeutic monitoring.

With the progression of chronic kidney disease, many molecules accumulate as a result of decreased kidney excretion capacity, such as compounds called uremic toxins. The investigators research is part of the European network for the study of these toxins (Eutox group) and has largely contributed to the better knowledge of these toxins. In particular, they are defined by their dose-dependent deleterious effects. These molecules are classified, according to their molecular weight, into small molecules, medium molecules and molecules strongly bound to plasma proteins (p-cresyl sulphate [pCS], indoxyl sulphate [IS] and indol acetic acid [IAA]). This last group of protein will be evaluated in this project.

The majority of studies conducted on uremic toxins involve patients before end stage renal failure or dialysis patients. Only a few studies have focused on transplant patients. In addition, the relationship between serum concentrations of uremic toxins and immunosuppressive drug concentrations has never been studied to date.

the investigator research hypothesis is that, due to the strong plasma protein binding of calcineurin inhibitors, an interaction with protein-bound uremic toxins could alter drug concentrations that explain difficulties in reaching therapeutic targets.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 12, 2023
• Est. primary completion date: September 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• renal transplant patient followed at the University Hospital of Amiens and transplanted for over a year

• patient treated with a calcineurin inhibitor

• patient having a blood test for evaluation of calcineurin inhibitor concentrations by the toxicology pharmacology laboratory of the Amiens-Picardie University Hospital,

• patient affiliated with social security.

Exclusion Criteria:

• patient in phase of acute rejection of the graft,

• patient having opposed his participation,

• patient under guardianship or curatorship or deprived of public right

Related Conditions & MeSH terms

• Immunosuppression
• Kidney Transplant
• Sepsis
• Toxemia
• Uremic; Toxemia

Intervention

Other:
• calcineurin inhibitor dosage
The dosage of calcineurin inhibitors will be done as usual by the toxicology pharmacology laboratory of the CHU Amiens-Picardie. If the patient does not object, the determination of protein-bound uremic toxins from the rest of the collected blood tube will be performed using high performance liquid chromatography.

Locations

Country	Name	City	State
France	CHU Amiens	Amiens

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire, Amiens

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	plasma tacrolimus concentration without plasma uremic toxin adjustment		at day 0
Primary	plasma tacrolimus concentration with plasma uremic toxin adjustment		at day 0
Secondary	plasma ciclosporin concentration without plasma uremic toxin adjustment		at day 0
Secondary	plasma ciclosporin concentration with plasma uremic toxin adjustment		at day 0