Ischemia Reperfusion InjuryTOPVASNCT03978065
The Renal Transplant Outcome Prediction and Validation Study
A study testing Confocal microscopy in people with Ischemia Reperfusion Injury, run by Medical University Innsbruck.
Trial summary
The number of patients with end stage renal disease is increasing continuously and kidney transplantation is the preferred treatment modality. Modern immunosuppressive therapy has reduced the number of acute rejection episodes and increased one year allograft survival dramatically. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemia Reperfusion Injury
- What is being tested?
- Confocal microscopy
- How many people
- 113 participants
- Where
- No sites listed yet
- Study dates
- 11 Jun 2015to 31 Mar 2020
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Recipient age > 18 years
- First or second deceased donor kidney transplantation
- Panel reactive antibody frequency <50%
Who cannot join
- Combined kidney transplantation with another organ
- Living donor kidney transplantation
- TOPVAS is a interventional prospective cohort study and participation of patients in other randomized prospective interventional trials does not per se violate the protocol
About this study
Official title: The Renal Transplant Outcome Prediction and Validation Study (TOPVAS)
The number of patients with end stage renal disease is increasing continuously and kidney transplantation is the preferred treatment modality. Modern immunosuppressive therapy has reduced the number of acute rejection episodes and increased one year allograft survival dramatically. Nonetheless, 4% of allografts are lost beyond the first year annually due to a multifactorial process and the latter number has not changed for decades. One of the most important factors to determine long-term success after kidney transplantation is the quality of the donor organ. For example, transplantation of organs from elderly or extended criteria donors results in reduced allograft and patient survival.
In previous work, the investigators specifically focused on age-associated molecular signatures including telomere length and mRNA expression levels of the cell cycle inhibitors CDKN2A (p16INK4a) and CDKN1A (p21WAF1) and assessed these parameters in pre-implantation biopsies of 54 patients. In a linear regression analysis CDKN2A turned out to be the best single predictor for serum creatinine after 1 year followed by donor age and telomere length. A multiple linear regression analysis revealed that the combination of CDKN2A values and donor age yielded even higher predictive values. In another study the investigators were able to show an interaction between donor age and use of calcineurin inhibitors with regard to outcome after renal transplantation.
During these past activities an extensive set of whole genome transcriptomics profile information from zero hour biopsies and clinical follow-up data has been collected. In the TOPVAS study, existing data derived from 72 of the above mentioned set of biopsies (exclusion of live donor grafts) will be analysed with state of the art bioinformatical/system biology tools to derive a general (not purely age associated) prognostic biomarker panel for functional transplant outcome two years after transplantation. This marker panel will also be used to define organs preferentially suitable for MMF/tacrolimus based immunosuppression. Both panels will then be validated for their prognostic and predictive information on the long-term outcome after transplantation in a new independent patient population treated with tacrolimus and MMF. In addition to biomarker assessment and in pursue of identifying alternative and/or complementary parameters with predictive value , an advanced morphological investigation of tissue biopsy life stains will be performed employing an innovative cell viability staining technology ("BIOPSYCHRONOLOGY").
- Conditions
- Ischemia Reperfusion Injury
- Being tested
- Confocal microscopy
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Confocal microscopyDiagnostic test
For this purpose "live stains" will be combined with a confocal imaging setup equipped with 6 laser lines. A major advantage of this technique is that tissue specimens do not need to be fixed prior to analysis. Such an approach does not only allow tissue viability and integrity assessment in an unprecedented speed and accuracy, but also promises to shed new light into quality assessment and prognosis in kidney transplantation. The investigators herein wish to establish the predictive values of this technology in kidney transplantation.
The methodology used in this trial is referred to as BIOPSYCHRONOLOGY - as a reference to dendrochronology, or tree ring dating. Leaving the biopsy sample intact facilitates its analysis, just as drills are used for tree-ring counting.
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of dialysis in the first 7 days post transplant
The need of at least one dialysis within the first 7 days post transplant.
Measured: 7 days
Kidney parenchyma quality
Live and dead cells in the kidney biopsy will be quantified using the dyes Syto-16/PI and WGA will be calculated as follows:
Groups: The number of dead/live cells will be entered in the following groups
- Total count (irrespective of localization).
- Tubular area (cells from the tubular area)
- Glomerular area (cells from the glomerulus) For each group the number of viable cells will be divided by the number of dead cells. (+1) Using this approach we will obtain for highly viable biopsies/areas high numbers, bigger than (0) For biopsies/areas in which the number of viable cells equals the one of dead cells we will obtain 1. (-1) For those in which the number of dead cells outnumbers the one of live cells, numbers between 1 and 0 will be obtained.
For each biopsy, a score will be calculated which will consist of the two tubular areas and the glomerular area. Therefore a maximum of +3 points can be achieved, or in the worst case -3.
Measured: before transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2019
- Study start11 Jun 2015
- Primary completion31 Mar 2020 (estimated)
- Study completion31 Mar 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemia Reperfusion InjuryStudies 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective, single-center pilot study
- Masking
- None (open label)
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University Innsbruck
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03978065
- Sponsor's protocol ID
- Version 1.1
- Acronym
- TOPVAS
- Status last verified
- Mar 2019
- First submitted
- 4 Mar 2019
- Last updated
- 26 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Renal Transplant Outcome Prediction and Validation Study (TOPVAS)
- ClinicalTrials.gov ID
- NCT03978065
- Acronym / sponsor ID
- TOPVAS / Version 1.1
- Conditions
- Ischemia Reperfusion Injury
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Medical University InnsbruckUniversity, hospital or other
- Study start
- 11 Jun 2015 (actual)
- Primary completion
- 31 Mar 2020 (estimated)
- Study completion
- 31 Mar 2020 (estimated)
- First posted
- 6 Jun 2019 (actual)
- 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.
The number of patients with end stage renal disease is increasing continuously and kidney transplantation is the preferred treatment modality. Modern immunosuppressive therapy has reduced the number of acute rejection episodes and increased one year allograft survival dramatically. Nonetheless, 4% of allografts are lost beyond the first year annually due to a multifactorial process and the latter number has not changed for decades. One of the most important factors to determine long-term success after kidney transplantation is the quality of the donor organ. For example, transplantation of organs from elderly or extended criteria donors results in reduced allograft and patient survival.
In previous work, the investigators specifically focused on age-associated molecular signatures including telomere length and mRNA expression levels of the cell cycle inhibitors CDKN2A (p16INK4a) and CDKN1A (p21WAF1) and assessed these parameters in pre-implantation biopsies of 54 patients. In a linear regression analysis CDKN2A turned out to be the best single predictor for serum creatinine after 1 year followed by donor age and telomere length. A multiple linear regression analysis revealed that the combination of CDKN2A values and donor age yielded even higher predictive values. In another study the investigators were able to show an interaction between donor age and use of calcineurin inhibitors with regard to outcome after renal transplantation.
During these past activities an extensive set of whole genome transcriptomics profile information from zero hour biopsies and clinical follow-up data has been collected. In the TOPVAS study, existing data derived from 72 of the above mentioned set of biopsies (exclusion of live donor grafts) will be analysed with state of the art bioinformatical/system biology tools to derive a general (not purely age associated) prognostic biomarker panel for functional transplant outcome two years after transplantation. This marker panel will also be used to define organs preferentially suitable for MMF/tacrolimus based immunosuppression. Both panels will then be validated for their prognostic and predictive information on the long-term outcome after transplantation in a new independent patient population treated with tacrolimus and MMF. In addition to biomarker assessment and in pursue of identifying alternative and/or complementary parameters with predictive value , an advanced morphological investigation of tissue biopsy life stains will be performed employing an innovative cell viability staining technology ("BIOPSYCHRONOLOGY").
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Model description
- Prospective, single-center pilot study
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Written informed consent
- Recipient age > 18 years
- First or second deceased donor kidney transplantation
- Panel reactive antibody frequency <50%
Key exclusion criteria (3 listed)
- Combined kidney transplantation with another organ
- Living donor kidney transplantation
- TOPVAS is a interventional prospective cohort study and participation of patients in other randomized prospective interventional trials does not per se violate the protocol
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 |
|---|---|---|
| Confocal microscopyFor this purpose "live stains" will be combined with a confocal imaging setup equipped with 6 laser lines. A major advantage of this technique is that tissue specimens do not need to be fixed prior to analysis. Such an approach does not only allow tissue viability and integrity assessment in an unprecedented speed and accuracy, but also promises to shed new light into quality assessment and prognosis in kidney transplantation. The investigators herein wish to establish the predictive values of this technology in kidney transplantation. The methodology used in this trial is referred to as BIOPSYCHRONOLOGY - as a reference to dendrochronology, or tree ring dating. Leaving the biopsy sample intact facilitates its analysis, just as drills are used for tree-ring counting. | Diagnostic test | – |
Primary outcome
The number of dialysis in the first 7 days post transplant
Time frame: 7 days
The need of at least one dialysis within the first 7 days post transplant.
Kidney parenchyma quality
Time frame: before transplant
Live and dead cells in the kidney biopsy will be quantified using the dyes Syto-16/PI and WGA will be calculated as follows: Groups: The number of dead/live cells will be entered in the following groups 1. Total count (irrespective of localization). 2. Tubular area (cells from the tubular area) 3. Glomerular area (cells from the glomerulus) For each group the number of viable cells will be divided by the number of dead cells. (+1) Using this approach we will obtain for highly viable biopsies/areas high numbers, bigger than (0) For biopsies/areas in which the number of viable cells equals the one of dead cells we will obtain 1. (-1) For those in which the number of dead cells outnumbers the one of live cells, numbers between 1 and 0 will be obtained. For each biopsy, a score will be calculated which will consist of the two tubular areas and the glomerular area. Therefore a maximum of +3 points can be achieved, or in the worst case -3.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2019.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Confocal microscopy in people with Ischemia Reperfusion Injury, run by Medical University Innsbruck.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 26 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
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?
The number of dialysis in the first 7 days post transplant (time frame: 7 days). The study lists 2 primary outcomes in all. 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 26 Jul 2019.