Type 2 DiabetesPhase 4NCT00588172
Genetic Variation in OCT1 and Response to Metformin
A Phase 4 study testing Metformin in people with Type 2 Diabetes, run by Mayo Clinic.
Trial summary
Type 2 diabetes its microvascular and macrovascular complications have become a major global health problem. Metformin is often used as first-line therapy for this disorder given that it is cheap, may cause weight loss and does not have significant side-effects in healthy patients. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2010to Jun 2011
- Phase
- Phase 4
- 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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Heterozygous or homozygous for the nsSNPs R61C, G401S, 420Del, G465R, G174S (see supplementary info (3)) or without any nsSNPs that could potentially alter gene function.
- Age 18 - 40.
- Willingness to participate in this study.
Who cannot join
- Fasting glucose > 100mg/dL on one occasion.
- Use of medication other than stable thyroid hormone replacement or oral contraception.
- Subjects must not be pregnant or < 6 months postpartum at the time of study.
- Prior abdominal surgery other than hysterectomy, appendectomy or tubal ligation.
About this study
Type 2 diabetes its microvascular and macrovascular complications have become a major global health problem. Metformin is often used as first-line therapy for this disorder given that it is cheap, may cause weight loss and does not have significant side-effects in healthy patients. On the other hand, as many as one third of all patients with type 2 diabetes initially treated with metformin never achieve a meaningful response to this intervention. Recently, genetic variation in the organic cation transporter 1 (Oct1) gene which encodes a protein, OCT1, mediating metformin uptake by the liver, its primary site of action, has been shown alter metformin action. In Oct1-deficient mice the glucose-lowering effects of metformin are completely abolished. Moreover a polymorphism with a 20% minor allele frequency in Caucasians also alters the effect of metformin on glucose tolerance (the net result of glucose uptake and glucose release) after ingestion of 75g of glucose. However, it is unknown if this polymorphism affects suppression of endogenous glucose production or stimulation of peripheral glucose uptake by metformin, or both, and to what degree. We propose to utilize established methodology to measure glucose turnover in response to a mixed meal to determine how common genetic variation in OCT1 alters response to metformin in healthy volunteers. This will clarify the effect of these variants on response to metformin in humans. The knowledge gained from this study will help to design future studies examining the role of OCT1 genotype in determining initial therapy for type 2 diabetes.
- Conditions
- Type 2 Diabetes
- Being tested
- Metformin
- Keywords
- Metformin, Type 2 diabetes, Oct1
- Medical subject headings
- Diabetes Mellitus, Type 2, Neurofibromatosis, Type 3, mixed central and peripheral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
1000mg bid for 1 week
| Study group | Role | What they receive |
|---|---|---|
| 1 | Sham comparator | Individuals with no nsSNPs or mutations known to alter oct1 function Receives: Drug: Metformin |
| 2 | Active comparator | Individuals with nsSNPs or mutations known to alter oct1 function Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in glucose area under the curve after a mixed meal in response to metformin
Measured: before and after 1 week of metformin
Secondary outcomes (1)
Change in glucose disappearance and suppression of endogenous glucose production in response to metformin
Measured: before and after 1 week of metformin therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2008 (estimated)
- Study startJun 2010
- Primary completionJun 2010
- Study completionJun 2011 (estimated)
Why it stopped: No funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Investigators
- Adrian Vella, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00588172
- Sponsor's protocol ID
- 07-004310
- Other IDs
- OCT1 and metformin
- Status last verified
- Aug 2010
- First submitted
- 22 Dec 2007
- Last updated
- 17 Aug 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Variation in OCT1 and Response to Metformin
- ClinicalTrials.gov ID
- NCT00588172
- Acronym / sponsor ID
- 07-004310
- Conditions
- Type 2 Diabetes
- Keywords
- Metformin, Type 2 diabetes, Oct1
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Jun 2010
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2011 (estimated)
- First posted
- 8 Jan 2008 (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.
Type 2 diabetes its microvascular and macrovascular complications have become a major global health problem. Metformin is often used as first-line therapy for this disorder given that it is cheap, may cause weight loss and does not have significant side-effects in healthy patients. On the other hand, as many as one third of all patients with type 2 diabetes initially treated with metformin never achieve a meaningful response to this intervention. Recently, genetic variation in the organic cation transporter 1 (Oct1) gene which encodes a protein, OCT1, mediating metformin uptake by the liver, its primary site of action, has been shown alter metformin action. In Oct1-deficient mice the glucose-lowering effects of metformin are completely abolished. Moreover a polymorphism with a 20% minor allele frequency in Caucasians also alters the effect of metformin on glucose tolerance (the net result of glucose uptake and glucose release) after ingestion of 75g of glucose. However, it is unknown if this polymorphism affects suppression of endogenous glucose production or stimulation of peripheral glucose uptake by metformin, or both, and to what degree. We propose to utilize established methodology to measure glucose turnover in response to a mixed meal to determine how common genetic variation in OCT1 alters response to metformin in healthy volunteers. This will clarify the effect of these variants on response to metformin in humans. The knowledge gained from this study will help to design future studies examining the role of OCT1 genotype in determining initial therapy for type 2 diabetes.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Sham comparator | Drug: MetforminIndividuals with no nsSNPs or mutations known to alter oct1 function |
| 2 | Active comparator | Drug: MetforminIndividuals with nsSNPs or mutations known to alter oct1 function |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Heterozygous or homozygous for the nsSNPs R61C, G401S, 420Del, G465R, G174S (see supplementary info (3)) or without any nsSNPs that could potentially alter gene function.
- Age 18 - 40.
- Willingness to participate in this study.
Key exclusion criteria (4 listed)
- Fasting glucose > 100mg/dL on one occasion.
- Use of medication other than stable thyroid hormone replacement or oral contraception.
- Subjects must not be pregnant or < 6 months postpartum at the time of study.
- Prior abdominal surgery other than hysterectomy, appendectomy or tubal ligation.
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 |
|---|---|---|
| Metformin1000mg bid for 1 week | Drug | 1, 2 |
Primary outcome
Change in glucose area under the curve after a mixed meal in response to metformin
Time frame: before and after 1 week of metformin
1 secondary outcome
Change in glucose disappearance and suppression of endogenous glucose production in response to metformin
Time frame: before and after 1 week of metformin therapy
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2010.
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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.
Adrian Vella, MD principal investigator
Mayo Clinic
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin in people with Type 2 Diabetes, run by Mayo Clinic.
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: withdrawn, as of the sponsor's last update on 17 Aug 2010. 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. Some participants in this study may receive a placebo. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Change in glucose area under the curve after a mixed meal in response to metformin (time frame: before and after 1 week of metformin). 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 17 Aug 2010.