Other Conditions That May Be A Focus of Clinical AttentionPhase 4NCT00187720
Genetic Basis for Variation in the Renal Elimination of Metformin
A Phase 4 study testing Metformin in people with Other Conditions That May Be A Focus of Clinical Attention, run by University of California, San Francisco at 1 site in United States.
Trial summary
The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. We will study individuals with particular genotypes of the human organic cation transporter, (hOCT2), to test the hypothesis that genetic variation in hOCT2 is associated with variation… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Other Conditions That May Be A Focus of Clinical Attention
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- May 2002to Apr 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects have previously participated in the Study Of Pharmacogenetics In Ethnically Diverse Populations (SOPHIE) study.
- 18-40 years old
- Possess a pre-specified genotype for OCT2
Who cannot join
- Taking any regular medications other than vitamins.
- Individuals with anemia (hemoglobin < 12 g/dL), an elevation in liver enzymes to higher than double the respective normal value, or elevated creatinine concentrations (males ≥ 1.5 mg/dL, females ≥ 1.4 mg/dL)
- Pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
San Francisco General Hospital
San Francisco, California, 94143
About this study
The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. We will study individuals with particular genotypes of the human organic cation transporter, (hOCT2), to test the hypothesis that genetic variation in hOCT2 is associated with variation in the renal clearance of the antidiabetic agent, metformin.
Read the detailed description
The drug, which is used in the treatment of Type II diabetes, has a narrow therapeutic range. Its net renal clearance by secretion (i.e., renal clearance minus filtration clearance) ranges from approximately 100 ml/min to 800ml/min in normal, healthy subjects. Although many factors may contribute to inter-individual variation in renal secretory clearance, initial estimates of heritability (greater than 0.6) suggest that genetic factors play an important role in the renal secretion of metformin. Available evidence supports the idea that hOCT2 is the primary transporter involved in the first-step of renal secretion of metformin, i.e., uptake from the blood to the tubule cell across the basolateral membrane. In particular, (a) hOCT2 is the primary organic cation transporter on the basolateral membrane of the human kidney; and (b) metformin interacts with and is translocated by hOCT2 in heterologous expression systems.
In recent studies, we identified four variants (M165I, A270S, R400C, and K432Q) with ethnic-specific allele frequencies ≥1% [6] that have altered function in studies in heterologous expression systems. In addition, we identified a common haplotype of hOCT2 and one haplotype that contain the non-synonymous cSNP, A270S. We will determine whether variability in the renal secretory clearance of the model organic cation, metformin, in healthy individuals is associated with genetic variation in hOCT2. In particular, we will determine whether the renal clearance of metformin differs in individuals who are homozygous for the common haplotype of OCT2 (OCT2*1) and those who are heterozygous for the less common haplotype OCT2*3D, which we have identified in a comprehensive screen of ethnically identified DNA samples. We will also determine whether individuals who are heterozygous for the less common OCT2 variants, M165I, R400C and K432Q, have reduced renal clearances of metformin.
- Being tested
- Metformin
- Keywords
- Healthy Control
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called GLUCOPHAGE
Subjects will be given a single oral dose of 850 mg of metformin
| Study group | Role | What they receive |
|---|---|---|
| OCT2-variant Group | Experimental | Subjects with OCT2-variant genotype will be given a single oral dose of 850 mg of metformin. Receives: Drug: Metformin |
| OCT2-reference Group | Experimental | Subjects with OCT2-reference genotype will be given a single oral dose of 850 mg of metformin. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Renal Clearance of Metformin
To test whether individuals with genetic variants of the human organic cation transporter, OCT2, exhibit altered renal elimination of metformin we will measure the difference in renal clearance between reference and variant groups.
Measured: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startMay 2002
- Primary completionApr 2008
- Study completionApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Other Conditions That May Be A Focus of Clinical AttentionStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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 4
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kathleen M Giacomini, PhD, Principal investigator, University of California, San Francsico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00187720
- Sponsor's protocol ID
- 787
- Status last verified
- Dec 2012
- First submitted
- 13 Sep 2005
- Last updated
- 10 Jan 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Chen Y, Li S, Brown C, Cheatham S, Castro RA, Leabman MK, Urban TJ, Chen L, Yee SW, Choi JH, Huang Y, Brett CM, Burchard EG, Giacomini KM. Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin. Pharmacogenet Genomics. 2009 Jul;19(7):497-504. doi: 10.1097/FPC.0b013e32832cc7e9.
PubMed 19483665
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Basis for Variation in the Renal Elimination of Metformin
- ClinicalTrials.gov ID
- NCT00187720
- Acronym / sponsor ID
- 787
- Keywords
- Healthy Control
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- May 2002
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 10 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. We will study individuals with particular genotypes of the human organic cation transporter, (hOCT2), to test the hypothesis that genetic variation in hOCT2 is associated with variation in the renal clearance of the antidiabetic agent, metformin.
Detailed description
The drug, which is used in the treatment of Type II diabetes, has a narrow therapeutic range. Its net renal clearance by secretion (i.e., renal clearance minus filtration clearance) ranges from approximately 100 ml/min to 800ml/min in normal, healthy subjects. Although many factors may contribute to inter-individual variation in renal secretory clearance, initial estimates of heritability (greater than 0.6) suggest that genetic factors play an important role in the renal secretion of metformin. Available evidence supports the idea that hOCT2 is the primary transporter involved in the first-step of renal secretion of metformin, i.e., uptake from the blood to the tubule cell across the basolateral membrane. In particular, (a) hOCT2 is the primary organic cation transporter on the basolateral membrane of the human kidney; and (b) metformin interacts with and is translocated by hOCT2 in heterologous expression systems.
In recent studies, we identified four variants (M165I, A270S, R400C, and K432Q) with ethnic-specific allele frequencies ≥1% [6] that have altered function in studies in heterologous expression systems. In addition, we identified a common haplotype of hOCT2 and one haplotype that contain the non-synonymous cSNP, A270S. We will determine whether variability in the renal secretory clearance of the model organic cation, metformin, in healthy individuals is associated with genetic variation in hOCT2. In particular, we will determine whether the renal clearance of metformin differs in individuals who are homozygous for the common haplotype of OCT2 (OCT2*1) and those who are heterozygous for the less common haplotype OCT2*3D, which we have identified in a comprehensive screen of ethnically identified DNA samples. We will also determine whether individuals who are heterozygous for the less common OCT2 variants, M165I, R400C and K432Q, have reduced renal clearances of metformin.
Study design
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OCT2-variant Group | Experimental | Drug: MetforminSubjects with OCT2-variant genotype will be given a single oral dose of 850 mg of metformin. |
| OCT2-reference Group | Experimental | Drug: MetforminSubjects with OCT2-reference genotype will be given a single oral dose of 850 mg of metformin. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Subjects have previously participated in the Study Of Pharmacogenetics In Ethnically Diverse Populations (SOPHIE) study.
- 18-40 years old
- Possess a pre-specified genotype for OCT2
Key exclusion criteria (3 listed)
- Taking any regular medications other than vitamins.
- Individuals with anemia (hemoglobin < 12 g/dL), an elevation in liver enzymes to higher than double the respective normal value, or elevated creatinine concentrations (males ≥ 1.5 mg/dL, females ≥ 1.4 mg/dL)
- Pregnant or breastfeeding
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 |
|---|---|---|
| MetforminAlso: GLUCOPHAGESubjects will be given a single oral dose of 850 mg of metformin | Drug | OCT2-reference Group, OCT2-variant Group |
Primary outcome
Renal Clearance of Metformin
Time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours
To test whether individuals with genetic variants of the human organic cation transporter, OCT2, exhibit altered renal elimination of metformin we will measure the difference in renal clearance between reference and variant groups.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19483665Chen Y, Li S, Brown C, Cheatham S, Castro RA, Leabman MK, Urban TJ, Chen L, Yee SW, Choi JH, Huang Y, Brett CM, Burchard EG, Giacomini KM. Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin. Pharmacogenet Genomics. 2009 Jul;19(7):497-504. doi: 10.1097/FPC.0b013e32832cc7e9.
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.
Kathleen M Giacomini, PhD principal investigator
University of California, San Francsico
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin in people with Other Conditions That May Be A Focus of Clinical Attention, run by University of California, San Francisco at 1 site in United States.
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 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: finished, as of the sponsor's last update on 10 Jan 2013. 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 United States. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Renal Clearance of Metformin (time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00187720, which also lists 1 linked publication.
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 10 Jan 2013.