Safety and Efficacy of the Addition of Alanyl-Glutamine-Dipeptide to Dialysis Solution in Peritoneal Dialysis

This study has been terminated.
(Primary endpoint (heat shock proteins) cannot be analyzed with the described laboratory method as specified in the protocol.)
Sponsor:
Information provided by (Responsible Party):
Christoph Aufricht, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01353638
First received: May 5, 2011
Last updated: June 12, 2012
Last verified: June 2012

May 5, 2011
June 12, 2012
April 2011
March 2012   (final data collection date for primary outcome measure)
Primary Endpoint: Total heat shock expression in peritoneal cells from dialysate samples; [ Time Frame: up to 70 days ] [ Designated as safety issue: No ]
In this study, an increase of total heat shock protein expression will be detected in cells from the peritoneal effluent at 240 min by staining of the cytospin and by Western blot analysis of the cellular pellet of the effluent. Total heat shock expression from dialysate samples is calculated in percent.
Same as current
Complete list of historical versions of study NCT01353638 on ClinicalTrials.gov Archive Site
  • Clinical PET-test to measure specific transport kinetics in peritoneal cells (creatinine, urea, sodium, potassium, phosphor, glucose, protein) [ Time Frame: up to 70 days ] [ Designated as safety issue: No ]
    The ratio of solute concentrations in dialysate and plasma (D/P ratio) at specific times (t) during the dwell signifies the extent of solute equilibration. Creatinine, glucose, urea, electrolytes, phosphate, and proteins are the commonly tested solutes for clinical use, in this study alanine, glutamine and alanyl-glutamine-dipeptide also will be measured to allow assessment of the respective resorption kinetics.
  • Cell number in peritoneal effluent; [ Time Frame: up to 70 days ] [ Designated as safety issue: No ]
    At the end of PD, total peritoneal cell count of the dialysate is measured; Unit of measurement: cells/µl
  • cytokines (IL-6, IL-8, TNFα); [ Time Frame: up to 70 days ] [ Designated as safety issue: No ]
    At the end of PD cytokines contained in the dialysate are being analysed. Unit of measurement: pg/ml
  • Cell function (phagocytosis and cytokine production) [ Time Frame: up to 70 days ] [ Designated as safety issue: No ]
    Analysis of cell function in dialysate at the end of PD by declaring the contingent of positive cell function in percent;
  • Morphology of peritoneal cells from effluent (cell culture) [ Time Frame: up to 70 days ] [ Designated as safety issue: No ]
    At the end of PD, the cells contained in the dialysate are being differentiated in following categories: ephitelium; non epithelium; mixed.
  • Biomarker CA125 [ Time Frame: up to 70 days ] [ Designated as safety issue: No ]
    At the end of PD, the amount of CA125 in the dialysate is measured in U/ml.
  • Tolerability/safety endpoints: No. and severity of AEs [ Time Frame: up to 70 days ] [ Designated as safety issue: Yes ]
    During the trial and after signing informed consent, the presence/absence/severity of AEs occurring to patients is being documented. Measurement parameter is no. and severity of AEs (including SAEs and SUSARs).
Same as current
Not Provided
Not Provided
 
Safety and Efficacy of the Addition of Alanyl-Glutamine-Dipeptide to Dialysis Solution in Peritoneal Dialysis
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)

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.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
End Stage Renal Disease
Drug: Dipeptiven (Alanyl-glutamine-dipeptide)
Two arms (A and B) and two treatment periods (1 and 2) are scheduled for this study. Each arm includes 14 patients. Schedule arm A: Treatment period 1 with one single peritoneal dialysis exchange (standard PD solution) with Alanyl-Glutamine-Dipeptide as add-on. 17,4 ml Dipeptiven (=3,48g N(2)-L Alanyl-L-Glutamin) will be dissolved at a final concentration of 0,174 %(= 8 mmol/l) in 2 liters of Dianeal®PD4 (at PH:5,5; Glucose-Concentration 3,86 %). After a wash out period (28 days + max 7 days), arm A undergoes treatment period 2, that is one single peritoneal dialysis exchange with standard PD solution without Alanyl-Glutamine-Dipeptide. Schedule Arm B: Treatment period 1 with one single peritoneal dialysis exchange with standard PD solution without Alanyl-Glutamine-Dipeptide followed by wash-out. Treatment period 2 for arm B includes one single peritoneal dialysis exchange with standard PD solution with Alanyl-Glutamine-Dipeptide as add-on. Dosages remain exactly the same.
Other Name: Standard PD solution: Dianeal® PD4 Glukose 3,86%
  • Arm A
    Arm A includes 14 patients. In treatment period 1, arm A receives standard PDF with the interventional drug alanyl-glutamine-dipeptide as add-on. As it is a cross-over study design, in treatment period 2, group A receives standard PDF without add-on.
    Intervention: Drug: Dipeptiven (Alanyl-glutamine-dipeptide)
  • Arm B
    Arm B includes 14 patients who in treatment period 1 receive standard PDF without the investigational drug. As it is a cross-over study design, in treatment period 2 arm B receives standard PDF with alanyl-glutamine-dipeptide as add-on.
    Intervention: Drug: Dipeptiven (Alanyl-glutamine-dipeptide)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
25
May 2012
March 2012   (final data collection date for primary outcome measure)

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
Both
19 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Austria
 
NCT01353638
Ala-Gln in PD
Yes
Christoph Aufricht, Medical University of Vienna
Christoph Aufricht
Not Provided
Study Director: Christoph Aufricht, Univ.Prof.Dr. Medical University of Vienna
Medical University of Vienna
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP