End Stage Renal DiseasePhase 1/2NCT01353638
Safety and Efficacy of the Addition of Alanyl-Glutamine-Dipeptide to Dialysis Solution in Peritoneal Dialysis
A Phase 1/2 study testing Dipeptiven (Alanyl-glutamine-dipeptide) in people with End Stage Renal Disease, run by Christoph Aufricht at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- End Stage Renal Disease
- What is being tested?
- Dipeptiven (Alanyl-glutamine-dipeptide)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteAustria
- Study dates
- Apr 2011to May 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- Clinical significant inflammatory parameters
- Less than 50 kg body weight
- Immunosuppressive therapy
Trial locations and contacts
1 site in 1 country.
Austria1 site
Department of Internal Medicine III; Clinical Division of Nephrology and Dialysis; Medical University of Vienna
Vienna, 1090
About this study
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)
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).
Read more
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
- Being tested
- Dipeptiven (Alanyl-glutamine-dipeptide)
- Keywords
- Peritoneal dialysis, Alanyl-Glutamine-Dipeptide, Heat shock protein, Peritoneal cells, functional maintenance of the peritoneal membrane
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dipeptiven (Alanyl-glutamine-dipeptide)Drug
Also called Standard PD solution: Dianeal® PD4 Glukose 3,86%
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Dipeptiven (Alanyl-glutamine-dipeptide) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: up to 70 days
Cell number in peritoneal effluent;
At the end of PD, total peritoneal cell count of the dialysate is measured; Unit of measurement: cells/µl
Measured: up to 70 days
cytokines (IL-6, IL-8, TNFα);
At the end of PD cytokines contained in the dialysate are being analysed. Unit of measurement: pg/ml
Measured: up to 70 days
Cell function (phagocytosis and cytokine production)
Analysis of cell function in dialysate at the end of PD by declaring the contingent of positive cell function in percent;
Measured: up to 70 days
Morphology of peritoneal cells from effluent (cell culture)
At the end of PD, the cells contained in the dialysate are being differentiated in following categories: ephitelium; non epithelium; mixed.
Measured: up to 70 days
Biomarker CA125
At the end of PD, the amount of CA125 in the dialysate is measured in U/ml.
Measured: up to 70 days
Tolerability/safety endpoints: No. and severity of AEs
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).
Measured: up to 70 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2011 (estimated)
- Study startApr 2011
- Primary completionMar 2012
- Study completionMay 2012
Why it stopped: Primary endpoint (HSP) could not be analyzed with the specified method in the planned interim analysis; a method of increased sensitivity had to be established.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christoph Aufricht
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Christoph Aufricht, Medical University of Vienna
- Investigators
- Christoph Aufricht, Univ.Prof.Dr., Study director, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01353638
- Sponsor's protocol ID
- Ala-Gln in PD
- Status last verified
- Sep 2015
- First submitted
- 5 May 2011
- Last updated
- 11 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01353638
- Acronym / sponsor ID
- Ala-Gln in PD
- Conditions
- End Stage Renal Disease
- Keywords
- Peritoneal dialysis, Alanyl-Glutamine-Dipeptide, Heat shock protein, Peritoneal cells, functional maintenance of the peritoneal membrane
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Primary endpoint (HSP) could not be analyzed with the specified method in the planned interim analysis; a method of increased sensitivity had to be established.
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Christoph AufrichtUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 13 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Other | Drug: Dipeptiven (Alanyl-glutamine-dipeptide)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. |
| Arm B | Other | Drug: Dipeptiven (Alanyl-glutamine-dipeptide)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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dipeptiven (Alanyl-glutamine-dipeptide)Also: Standard PD solution: Dianeal® PD4 Glukose 3,86%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. | Drug | Arm A, Arm B |
Primary outcome
Primary Endpoint: Total heat shock expression in peritoneal cells from dialysate samples;
Time frame: up to 70 days
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.
7 secondary outcomes
Clinical PET-test to measure specific transport kinetics in peritoneal cells (creatinine, urea, sodium, potassium, phosphor, glucose, protein)
Time frame: up to 70 days
Cell number in peritoneal effluent;
Time frame: up to 70 days
cytokines (IL-6, IL-8, TNFα);
Time frame: up to 70 days
Cell function (phagocytosis and cytokine production)
Time frame: up to 70 days
Morphology of peritoneal cells from effluent (cell culture)
Time frame: up to 70 days
Biomarker CA125
Time frame: up to 70 days
Tolerability/safety endpoints: No. and severity of AEs
Time frame: up to 70 days
Results and safety
The study was stopped early (reason given: Primary endpoint (HSP) could not be analyzed with the specified method in the planned interim analysis; a method of increased sensitivity had to be established.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2015.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christoph Aufricht, Univ.Prof.Dr. study director
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dipeptiven (Alanyl-glutamine-dipeptide) in people with End Stage Renal Disease, run by Christoph Aufricht at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Primary endpoint (HSP) could not be analyzed with the specified method in the planned interim analysis; a method of increased sensitivity had to be established.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Endpoint: Total heat shock expression in peritoneal cells from dialysate samples; (time frame: up to 70 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2015.