Adverse EffectsNCT00251017
Impact of Polymorphisms of OAT1, OAT3, and OCT2 on Transportation of Potential Nephrotoxic Drugs
A study testing Vancomycin and DNA are extracted from the whole blood of subjects in people with Adverse Effects, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
Transporters in kidney are critical in detoxification and elimination of xenobiotics from systemic circulation, and thus are major determinants of drug response and sensitivity. Transporters in the renal epithelium control the exposure of renal cells to nephrotoxic drugs and environmental toxins and thus determine… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Adverse Effects
- What is being tested?
- Vancomycin and DNA are extracted from the whole blood of subjects
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteTaiwan
- Study dates
- Jul 2005to Jun 2006
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects 16 years of age or older, of either sex.
- Subjects have a medication including vancomycin
- Subjects have realistic expectations of the benefit and limitation of the augmentation procedure, as determined by a willingness to sign the informed consent form after it has been carefully explained.
Who cannot join
- Subjects have a medical condition that increased the risks of study participation (including pregnancy and poor renal function)
- Subjects are taking medications (nephrotoxicants) that could confound study results.
- Subjects presenting with history of autoimmune disorder, septic shock, or multiple organ failure.
- Subjects with renal failure undergoing dialysis (hemodialysis [HD] or continuous ambulatory peritoneal dialysis [CAPD]), continuous venovenous hemofiltration (CVVH), or continuous arteriovenous hemodiafiltration (CAVHDF).
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Department of Surgery, National Taiwan University Hospital
Taipei, 100
About this study
Transporters in kidney are critical in detoxification and elimination of xenobiotics from systemic circulation, and thus are major determinants of drug response and sensitivity. Transporters in the renal epithelium control the exposure of renal cells to nephrotoxic drugs and environmental toxins and thus determine xenobiotic-induced nephrotoxicity. Organic anion transporters (OATs) and organic cation transporters (OCTs) are two major classes of secretory transporters in the mammalian kidney. Among the uptake transporters, OAT1, OAT3, or OCT2 appear to be particularly important in the renal basolateral membrane to transport a large variety of endogenous and therapeutic compounds.
Recently, rapid advances in single nucleotide polymorphisms (SNPs) mapping can now be applied to characterize the individual patients who suffer adverse effects to a drug, or those for whom a drug shows efficacy. The aim of this study was to identify and functionally characterize OCT2 variants as a first step towards understanding whether genetic variation in OCT2 may contribute to interindividual differences in renal elimination of vancomycin. Taiwanese patients will be screened and 12 coding region variants of OCT2 will be identified. The non-synonymous variants of OAT1, OAT3, or OCT2 will then be constructed and characterized using in vitro human renal cell models. It is to establish whether genetic variants in OAT1, OAT3, or OCT2 are likely significant contributors to intersubject variability in drug response. In addition, approaches toward prevention of some drug-induced nephrotoxicity are discussed, based on molecular mechanisms of renal accumulation of these drugs. Perhaps the researchers' understanding of OAT1, OAT3, or OCT2 in pharmacogenomics may contribute to the goal of individualized drug therapy. Development of new strategies based on the understanding of their cellular handing may achieve safer and more effective therapy for personalized medicines.
Read the detailed description
Beta-lactam antibiotics, aminoglycosides, amphotericin B, cyclosporine, nonsteroidal anti-inflammatory drugs, antineoplastic, or antivirus drugs that are used extensively in clinical settings bear the risk of nephrotoxicity. This side effect is dose-dependent and has been attributed mainly to the accumulation of drugs in the renal proximal tubule. When assessing nephrotoxicity, both the dosage and the tubular secretion system, which allows transport of drug from blood to urine via the tubular cells, are important factors. This study was designed to investigate how renal transporters work in the renal secretion of specific drugs.
Transporters in kidney are critical in detoxification and elimination of xenobiotics from systemic circulation, and thus are major determinants of drug response and sensitivity. Transporters in the renal epithelium control the exposure of renal cells to nephrotoxic drugs and environmental toxins and thus determine xenobiotic-induced nephrotoxicity. Organic anion transporters (OATs) and organic cation transporters (OCTs) are two major classes of secretory transporters in the mammalian kidney. Among the uptake transporters, OAT1, OAT3, or OCT2 appear to be particularly important in the renal basolateral membrane to transport a large variety of endogenous and therapeutic compounds.
Recently, rapid advances in single nucleotide polymorphisms (SNPs) mapping can now be applied to characterize the individual patients who suffer adverse effects to a drug, or those for whom a drug shows efficacy. The aim of this study was to identify and functionally characterize OCT2 variants as a first step towards understanding whether genetic variation in OCT2 may contribute to interindividual differences in renal elimination of vancomycin. Taiwanese patients will be screened and 12 coding region variants of OCT2 will be identified. The non-synonymous variants of OAT1, OAT3, or OCT2 will then be constructed and characterized using in vitro human renal cell models. It is to establish whether genetic variants in OAT1, OAT3, or OCT2 are likely significant contributors to intersubject variability in drug response. In addition, approaches toward the prevention of some drug-induced nephrotoxicity are discussed, base on molecular mechanisms of renal accumulation of these drugs. Perhaps our understanding of OAT1, OAT3, or OCT2 in pharmacogenomics may contribute to the goal of individualized drug therapy. Development of new strategies based on the understanding of their cellular handing may achieve safer and more effective therapy for personalized medicines.
- Conditions
- Adverse Effects
- Being tested
- Vancomycin, DNA are extracted from the whole blood of subjects
- Keywords
- single nucleotide polymorphisms (SNPs), personalized medicines, Subjects 16 years of age or older, of either sex., Subjects have a medication including vancomycin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VancomycinProcedure or surgery
Two hour creatinine clearance before and after vancomycin
DNA are extracted from the whole blood of subjectsProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Vancomycin | Active comparator | Effects of OCT2 genetic variation in renal elimination of Vancomycin Receives: Procedure: Vancomycin; Procedure: DNA are extracted from the whole blood of subjects |
What is being measured
The primary outcome is the main question the study is designed to answer.
Single nucleotide polymorphism (SNP), plasma creatinine and vancomycin concentration
Measured: 0, 2 hour after Vancomycin administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2005 (estimated)
- Study startJul 2005
- Primary completionJun 2006
- Study completionJun 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adverse EffectsStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Department of Health, Executive Yuan, R.O.C. (Taiwan)
- Responsible party
- Sponsor
- Investigators
- Ji-Wang Chern, Ph.D., Study chair, National Taiwan UniversityWen-Je Ko, M.D, Ph.D, Principal investigator, National Taiwan University HospitalFe-Lin Lin, Ph.D., Principal investigator, National of UniversityChiung-Hua Huang, M.S, Study director, National Taiwan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00251017
- Sponsor's protocol ID
- 9361701301
- Other IDs
- DOH94-td-d-113-035(2)
- Status last verified
- Dec 2012
- First submitted
- 8 Nov 2005
- Last updated
- 27 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Polymorphisms of OAT1, OAT3, and OCT2 on Transportation of Potential Nephrotoxic Drugs
- ClinicalTrials.gov ID
- NCT00251017
- Acronym / sponsor ID
- 9361701301
- Conditions
- Adverse Effects
- Keywords
- single nucleotide polymorphisms (SNPs), personalized medicines, Subjects 16 years of age or older, of either sex., Subjects have a medication including vancomycin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- Department of Health, Executive Yuan, R.O.C. (Taiwan)
- Study start
- Jul 2005
- Primary completion
- Jun 2006 (actual)
- Study completion
- Jun 2006 (actual)
- First posted
- 9 Nov 2005 (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.
Transporters in kidney are critical in detoxification and elimination of xenobiotics from systemic circulation, and thus are major determinants of drug response and sensitivity. Transporters in the renal epithelium control the exposure of renal cells to nephrotoxic drugs and environmental toxins and thus determine xenobiotic-induced nephrotoxicity. Organic anion transporters (OATs) and organic cation transporters (OCTs) are two major classes of secretory transporters in the mammalian kidney. Among the uptake transporters, OAT1, OAT3, or OCT2 appear to be particularly important in the renal basolateral membrane to transport a large variety of endogenous and therapeutic compounds.
Recently, rapid advances in single nucleotide polymorphisms (SNPs) mapping can now be applied to characterize the individual patients who suffer adverse effects to a drug, or those for whom a drug shows efficacy. The aim of this study was to identify and functionally characterize OCT2 variants as a first step towards understanding whether genetic variation in OCT2 may contribute to interindividual differences in renal elimination of vancomycin. Taiwanese patients will be screened and 12 coding region variants of OCT2 will be identified. The non-synonymous variants of OAT1, OAT3, or OCT2 will then be constructed and characterized using in vitro human renal cell models. It is to establish whether genetic variants in OAT1, OAT3, or OCT2 are likely significant contributors to intersubject variability in drug response. In addition, approaches toward prevention of some drug-induced nephrotoxicity are discussed, based on molecular mechanisms of renal accumulation of these drugs. Perhaps the researchers' understanding of OAT1, OAT3, or OCT2 in pharmacogenomics may contribute to the goal of individualized drug therapy. Development of new strategies based on the understanding of their cellular handing may achieve safer and more effective therapy for personalized medicines.
Detailed description
Beta-lactam antibiotics, aminoglycosides, amphotericin B, cyclosporine, nonsteroidal anti-inflammatory drugs, antineoplastic, or antivirus drugs that are used extensively in clinical settings bear the risk of nephrotoxicity. This side effect is dose-dependent and has been attributed mainly to the accumulation of drugs in the renal proximal tubule. When assessing nephrotoxicity, both the dosage and the tubular secretion system, which allows transport of drug from blood to urine via the tubular cells, are important factors. This study was designed to investigate how renal transporters work in the renal secretion of specific drugs.
Transporters in kidney are critical in detoxification and elimination of xenobiotics from systemic circulation, and thus are major determinants of drug response and sensitivity. Transporters in the renal epithelium control the exposure of renal cells to nephrotoxic drugs and environmental toxins and thus determine xenobiotic-induced nephrotoxicity. Organic anion transporters (OATs) and organic cation transporters (OCTs) are two major classes of secretory transporters in the mammalian kidney. Among the uptake transporters, OAT1, OAT3, or OCT2 appear to be particularly important in the renal basolateral membrane to transport a large variety of endogenous and therapeutic compounds.
Recently, rapid advances in single nucleotide polymorphisms (SNPs) mapping can now be applied to characterize the individual patients who suffer adverse effects to a drug, or those for whom a drug shows efficacy. The aim of this study was to identify and functionally characterize OCT2 variants as a first step towards understanding whether genetic variation in OCT2 may contribute to interindividual differences in renal elimination of vancomycin. Taiwanese patients will be screened and 12 coding region variants of OCT2 will be identified. The non-synonymous variants of OAT1, OAT3, or OCT2 will then be constructed and characterized using in vitro human renal cell models. It is to establish whether genetic variants in OAT1, OAT3, or OCT2 are likely significant contributors to intersubject variability in drug response. In addition, approaches toward the prevention of some drug-induced nephrotoxicity are discussed, base on molecular mechanisms of renal accumulation of these drugs. Perhaps our understanding of OAT1, OAT3, or OCT2 in pharmacogenomics may contribute to the goal of individualized drug therapy. Development of new strategies based on the understanding of their cellular handing may achieve safer and more effective therapy for personalized medicines.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vancomycin | Active comparator | Procedure: Vancomycin, Procedure: DNA are extracted from the whole blood of subjectsEffects of OCT2 genetic variation in renal elimination of Vancomycin |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Subjects 16 years of age or older, of either sex.
- Subjects have a medication including vancomycin
- Subjects have realistic expectations of the benefit and limitation of the augmentation procedure, as determined by a willingness to sign the informed consent form after it has been carefully explained.
Key exclusion criteria (4 listed)
- Subjects have a medical condition that increased the risks of study participation (including pregnancy and poor renal function)
- Subjects are taking medications (nephrotoxicants) that could confound study results.
- Subjects presenting with history of autoimmune disorder, septic shock, or multiple organ failure.
- Subjects with renal failure undergoing dialysis (hemodialysis [HD] or continuous ambulatory peritoneal dialysis [CAPD]), continuous venovenous hemofiltration (CVVH), or continuous arteriovenous hemodiafiltration (CAVHDF).
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 |
|---|---|---|
| VancomycinTwo hour creatinine clearance before and after vancomycin | Procedure or surgery | Vancomycin |
| DNA are extracted from the whole blood of subjects | Procedure or surgery | Vancomycin |
Primary outcome
Single nucleotide polymorphism (SNP), plasma creatinine and vancomycin concentration
Time frame: 0, 2 hour after Vancomycin administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2012.
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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.
Ji-Wang Chern, Ph.D. study chair
National Taiwan University
Wen-Je Ko, M.D, Ph.D principal investigator
National Taiwan University Hospital
Fe-Lin Lin, Ph.D. principal investigator
National of University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vancomycin and DNA are extracted from the whole blood of subjects in people with Adverse Effects, run by National Taiwan University Hospital at 1 site in Taiwan.
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 3 inclusion and 4 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: finished, as of the sponsor's last update on 27 Dec 2012. 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 Taiwan. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Single nucleotide polymorphism (SNP), plasma creatinine and vancomycin concentration (time frame: 0, 2 hour after Vancomycin administration). 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 27 Dec 2012.