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

NCT01353638 | Terminated Phase 1 DMC

• 1 other identifier: Ala-Gln in PD
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

End Stage Renal Disease

Keywords

Peritoneal dialysis; Alanyl-Glutamine-Dipeptide; Heat shock protein; Peritoneal cells; functional maintenance of the peritoneal membrane

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint: Total heat shock expression in peritoneal cells from dialysate samples;

  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.

  up to 70 days

Secondary Outcomes (7)

• Clinical PET-test to measure specific transport kinetics in peritoneal cells (creatinine, urea, sodium, potassium, phosphor, glucose, protein)

  up to 70 days

• Cell number in peritoneal effluent;

  up to 70 days

• cytokines (IL-6, IL-8, TNFα);

  up to 70 days

• Cell function (phagocytosis and cytokine production)

  up to 70 days

• Morphology of peritoneal cells from effluent (cell culture)

  up to 70 days

Study Arms (2)

Arm A

OTHER

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.

Drug: Dipeptiven (Alanyl-glutamine-dipeptide)

Arm B

OTHER

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.

Drug: Dipeptiven (Alanyl-glutamine-dipeptide)

Interventions

Dipeptiven (Alanyl-glutamine-dipeptide) DRUG

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.

Also known as: Standard PD solution: Dianeal® PD4 Glukose 3,86%

Arm A; Arm B

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Christoph Aufricht: lead

Study Sites (1)

Department of Internal Medicine III; Clinical Division of Nephrology and Dialysis; Medical University of Vienna

Vienna, 1090, Austria

Location

Related Links

• Related Info

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

alanylglutamine

Condition Hierarchy (Ancestors)

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

Study Officials

• Christoph Aufricht, Univ.Prof.Dr.

  Medical University of Vienna

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Ao.Univ.-Prof. Dr.med.univ.

Study Record Dates

• First Submitted: May 5, 2011
• First Posted: May 13, 2011
• Study Start: April 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: May 1, 2012
• Last Updated: September 11, 2015

Record last verified: 2015-09

Locations

AU (1)