Clinical trial NCT01353638: Safety and Efficacy of the Addition of Alanyl-Glutamine-Dipeptide to Dialysis Solution in Peritoneal Dialysis
Official title: An Open Label, Randomized, Two-Period Crossover Study to Evaluate the Safety and Efficacy of the Addition of Alanyl-Glutamine-Dipeptide to Dialysis Solutions in Peritoneal Dialysis (PD) (Ala-Gln in PD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: End Stage Renal Disease
Keywords: Peritoneal dialysis
Alanyl-Glutamine-Dipeptide
Heat shock protein
Peritoneal cells
functional maintenance of the peritoneal membrane
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2011-05-13
Enrollment: 25
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Peritoneal dialysis (PD) is a cost effective and safe form of renal replacement therapy in patients suffering from end stage renal disease.

However currently available PDF (peritoneal dialysis fluids) are not biocompatible for the peritoneal cavity and its cells. Acute cytotoxic effects of the majority of the current glucose-based PDF are caused by low pH, lactate, high glucose and its degradation products (GDP).

Toxic effects of PDF can thus be extended to suppression of mesothelial HSR (heat shock reactions) following PDF exposure resulting in increased susceptibility of mesothelial cells against PDF exposure: PDF inherent stress factors fail to adequately induce HSP as effectors of the cellular stress response - the adequate HRS rather seems to be blocked.

Hence, therapeutic approaches to activate and enhance the HSR will reduce peritoneal damage and organ failure and improve the survival of organisms.

Preclinical results demonstrated that supplementation of PDF with pharmacological doses of alanyl-glutamine restored HSP expression and increased the resistance of mesothelial cells in in-vitro models of PD and preserved peritoneal integrity in in-vivo models of PD.

After these positive preclinical results, this study shall now clarify, whether the addition of alanyl-glutamine to the most commonly used glucose-based PDF is safe and tolerable. Therefore PDFs will be drained in a randomized cross-over study. Main outcomes measures will be total HSP expression in peritoneal cells and changes of the peritoneal transport kinetics and the presence/absence/severity of side effects.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent prior to any study-mandated procedure
* Male and female patients aged ≥ 19 years old
* Chronic renal failure; 2 months stable on PD
* no peritonitis within the previous 2 months
* Without severe concomitant disease
* Negative pregnancy test in female patients of childbearing potential and adequate contraception in female patients of childbearing age

Exclusion Criteria:

* Known hypersensitivity to study medication
* Treatment with another investigational drug within 1 month prior to start of study medication
* Malignancy requiring chemotherapy or radiation
* Pregnancy or nursing,
* Presumed non-compliance
* Limited efficacy of peritoneal dialysis due to anatomical anomalies or severe intra-abdominal adhesions
* Clinical significant inflammatory parameters
* Less than 50 kg body weight
* Immunosuppressive therapy

Primary outcomes:
measure: Primary Endpoint: Total heat shock expression in peritoneal cells from dialysate samples;
timeFrame: up to 70 days
Secondary outcomes:
measure: Clinical PET-test to measure specific transport kinetics in peritoneal cells (creatinine, urea, sodium, potassium, phosphor, glucose, protein)
timeFrame: up to 70 days
measure: Cell number in peritoneal effluent;
timeFrame: up to 70 days
measure: cytokines (IL-6, IL-8, TNFα);
timeFrame: up to 70 days
measure: Cell function (phagocytosis and cytokine production)
timeFrame: up to 70 days
measure: Morphology of peritoneal cells from effluent (cell culture)
timeFrame: up to 70 days
measure: Biomarker CA125
timeFrame: up to 70 days
measure: Tolerability/safety endpoints: No. and severity of AEs
timeFrame: up to 70 days
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Department of Internal Medicine III; Clinical Division of Nephrology and Dialysis; Medical University of Vienna
Study officials:
affiliation: Medical University of Vienna
name: Christoph Aufricht, Univ.Prof.Dr.
role: STUDY_DIRECTOR
References: