Diabetes Mellitus, Type 2Phase 4NCT01045590
Glibenclamide (Dose to be Titrated From Starting Dose of 5mg om) Plus Rosiglitazone 4mg om (Increased to 8mg om After 6 Months) and vs Glibenclamide (Dose to be Titrated With Starting Dose of 5mg om) Plus Placebo, Administered to Patients With Type 2 Diabetes Mellitus
A Phase 4 study testing titration in people with Diabetes Mellitus, Type 2, run by GlaxoSmithKline at 4 sites in South Korea.
Trial summary
Rationale Rosiglitazone and troglitazone both promote differentiation of pre-adipocytes into adipocytes in subcutaneous, but not omental fat, and reduce gamma glutamyl transferase, a surrogate marker for intra-abdominal and hepatic fat. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- titration
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 4 sitesSouth Korea
- Study dates
- Dec 2003to Feb 2006
- 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 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Subjects were selected by following considerations:
- Diagnosis of type 2 diabetes mellitus defined by the American Diabetic Association (ADA) criteria.
- Subject whose diabetes was managed by diet, exercise, and/or sulfonylurea, and/or metformin, who could be converted to treatment with glibenclamide 5mg om.
- 126mg/dL ≤ fasting plasma glucose (FPG) ≤ 270mg/dL and HbA1c level >7% at screening. In addition, the following criterion was applied prior to randomization: 126mg/dL ≤ fasting plasma glucose (FPG) ≤ 270mg/dL at baseline(after 2 months of run-in treatment with glibenclamide 5mg om only).
Trial locations and contacts
4 sites in 1 country.
South Korea4 sites
GSK Investigational Site
Seoul, 110-744
GSK Investigational Site
Seoul, 120-752
GSK Investigational Site
Seoul, 135-710
GSK Investigational Site
Seoul, 137-701
About this study
Official title: Phase IV, Multicenter, Single-blind, Positive-controlled, Parallel Group Study of Glibenclamide (Dose to be Titrated From Starting Dose of 5mg om) Plus Rosiglitazone 4mg om (Increased to 8mg om After 6 Months) and vs Glibenclamide (Dose to be Titrated With Starting Dose of 5mg om) Plus Placebo, Adm
Rationale Rosiglitazone and troglitazone both promote differentiation of pre-adipocytes into adipocytes in subcutaneous, but not omental fat, and reduce gamma glutamyl transferase, a surrogate marker for intra-abdominal and hepatic fat. Troglitazone has been shown by abdominal computed tomography (CT) and magnetic resonance imaging (MRI) scan to reduce the intra-abdominal adipose tissue area in type 2 diabetics. Similarly rosiglitazone has also been shown to increase subcutaneous but not intra-abdominal fat in patients with type 2 diabetes. In the same study it was also shown to cause a substantial reduction in hepatic fat. Central fat depots are believed to be associated with more cardiovascular risk than subcutaneous fat depots. By contrast, sulphonylurea-associated weight gain has been shown by abdominal CT scan to include increases in intra-abdominal adipose tissue.
The aim of this study is to compare the body fat distribution pattern of glibenclamide plus rosiglitazone versus glibenclamide and placebo (especially the intra-abdominal adipose tissue and abdominal subcutaneous adipose tissue areas) in patients with type 2 diabetes. It is hypothesised that rosiglitazone will lead to the accumulation of excess energy stores in the subcutaneous rather than the intra-abdominal adipose tissue depot. In addition, it is hoped that by having a positive effect on diastolic blood pressure, lipid levels, BMI, rosiglitazone will be shown to have a better cardiovascular risk profile when used in combination with glibenclamide rather than when glibenclamide is used alone.
Read more
Although insulin resistance has been shown to be a primary defect causing type 2 diabetes mellitus, insulin secretory defect has also been known to be an important factor in the development of type 2 diabetes mellitus. A previous study has shown that in Korean patients, early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes mellitus [56].
This study also aims to assess the efficacy and safety of glibenclamide plus rosiglitazone versus glibenclamide plus placebo therapy in Korean patients with type 2 diabetes. In addition, a previous study has shown that in Korean patients, early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes mellitus. This study aims to show that rosiglitazone treatment in Korean patients, regardless of their early phase insulin secretory ability, is just as efficacious and safe.
Objective(s) Primary To evaluate the effect of 12 months oral treatment with glibenclamide plus rosiglitazone versus oral glibenclamide plus placebo, on body fat distribution (as measured by the change in the ratio between the intra-abdominal adipose tissue and abdominal subcutaneous adipose tissue areas) in patients with type 2 diabetes.
Secondary
- To investigate the efficacy of glibenclamide plus rosiglitazone, compared to glibenclamide plus placebo on beta-cell function and insulin resistance as calculated by HOMA-B and HOMA-R.
- To investigate the efficacy of glibenclamide plus rosiglitazone, compared to glibenclamide plus placebo on fasting plasma glucose, insulin, fasting serum lipid profile (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol to HDL cholesterol ratio).
- To investigate the efficacy of glibenclamide plus rosiglitazone, compared to glibenclamide plus placebo on early phase insulin secretion during an oral glucose tolerance test as measured by the insulinogenic index.
- To define further the clinical safety and tolerability of glibenclamide plus rosiglitazone through the assessment of physical examinations, vital signs, weight, routine laboratory tests, adverse experiences and electrocardiograms (ECGs).
Endpoint(s) Primary Change from baseline in the ratio (IAAT:SAT) between the intra-abdominal adipose tissue area (IAAT) and abdominal subcutaneous adipose tissue area [SAT] after 12 months treatment with oral glibenclamide plus rosiglitazone compared to oral glibenclamide plus placebo Secondary
Comparisons will be made between glibenclamide plus rosiglitazone and glibenclamide plus placebo treatment groups on Change from baseline after 6 and 12 months treatment with respect the following:
CT Scan
Derived from CT image at the lumbar IV level:
- abdominal subcutaneous adipose tissue area [SAT]
- intra-abdominal adipose tissue area [IAAT]
Derived from the CT image of the right leg at the thigh level (1cm below the gluteal fold):
- total subcutaneous adipose tissue area [TSAT] Derived from CT images at the lumbar IV and thigh level
- ratio between abdominal subcutaneous adipose tissue area [SAT] and total subcutaneous adipose tissue area of the thigh [TSAT]
- ratio between intra-abdominal adipose tissue area [IAAT] and total subcutaneous adipose tissue area of the thigh [TSAT] Derived from Oral Glucose Tolerance Test, glycaemic response to OGTT, difference
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- titration
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
titrationDrug
Patients in the glibenclamide plus placebo treatment group Patients in the glibenclamide plus placebo treatment group who have FPG < 270mg/dL after the glibenclamide 5mg om run-in will continue to receive glibenclamide 5mg om. At every subsequent visit, the glibenclamide dose will be titrated to achieve the target HbA1c level of < 7%. If the HbA1c is > 7%, the dose of glibenclamide will be escalated in the following sequence: from 5mg om, to 5mg om, 2.5mg on, to 5mg bd and 7.5mg om, 5mg on, to 7.5mg bd. The maximum total daily dose will not exceed 15 mg. A downward titration of glibenclamide using the above sequence in the reverse order can be used to maintain normoglycemia at any visit. Once the target HbA1c level of < 7% is achieved, the dose of glibenclamide is maintained. If at the glibenclamide dose of 7.5mg bd, the HbA1c is > 7% for 2 subsequent visits, the patient will be withdrawn from the study.
titrationDrug
Patients in the glibenclamide + rosiglitazone treatment group who have FPG < 270mg/dL after the glibenclamide 5mg om run-in will receive glibenclamide 5mg om + rosiglitazone 4mg om. At every subsequent visit, the glibenclamide dose will be titrated to achieve the target HbA1c level of < 7%. If the HbA1c is > 7%, the dose of glibenclamide will be escalated in a similar fashion as above. The only exception is at visit 5 when the dose of rosiglitazone is increased (see next paragraph). Once the target HbA1c level of < 7% is achieved, the dose of glibenclamide is maintained. If at the glibenclamide dose of 7.5mg bd, the HbA1c is > 7% for 2 subsequent visits, the patient will be withdrawn from the study.
| Study group | Role | What they receive |
|---|---|---|
| glibenclamide + Rosiglitazone | Active comparator | glibenclamide plus rosiglitazone Receives: Drug: titration |
| glibenclamide + placebo | Placebo comparator | Not described Receives: Drug: titration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in the ratio (IAAT:SAT) between the intra-abdominal adipose tissue area (IAAT) and abdominal subcutaneous adipose tissue area [SAT] after 12 months treatment with oral glibenclamide plus rosiglitazone compared to oral glibenclamide p
Measured: baseline
Secondary outcomes (1)
Comparisons will be made between glibenclamide plus rosiglitazone and glibenclamide plus placebo treatment groups on Change from baseline after 6 and 12 months treatment with respect the following
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2010 (estimated)
- Study startDec 2003
- Primary completionFeb 2006
- Study completionFeb 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01045590
- Sponsor's protocol ID
- 100684
- Status last verified
- Feb 2011
- First submitted
- 10 Dec 2009
- Last updated
- 18 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IV, Multicenter, Single-blind, Positive-controlled, Parallel Group Study of Glibenclamide (Dose to be Titrated From Starting Dose of 5mg om) Plus Rosiglitazone 4mg om (Increased to 8mg om After 6 Months) and vs Glibenclamide (Dose to be Titrated With Starting Dose of 5mg om) Plus Placebo, Adm
- ClinicalTrials.gov ID
- NCT01045590
- Acronym / sponsor ID
- 100684
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Dec 2003
- Primary completion
- Feb 2006 (actual)
- Study completion
- Feb 2006 (actual)
- First posted
- 11 Jan 2010 (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.
Rationale Rosiglitazone and troglitazone both promote differentiation of pre-adipocytes into adipocytes in subcutaneous, but not omental fat, and reduce gamma glutamyl transferase, a surrogate marker for intra-abdominal and hepatic fat. Troglitazone has been shown by abdominal computed tomography (CT) and magnetic resonance imaging (MRI) scan to reduce the intra-abdominal adipose tissue area in type 2 diabetics. Similarly rosiglitazone has also been shown to increase subcutaneous but not intra-abdominal fat in patients with type 2 diabetes. In the same study it was also shown to cause a substantial reduction in hepatic fat. Central fat depots are believed to be associated with more cardiovascular risk than subcutaneous fat depots. By contrast, sulphonylurea-associated weight gain has been shown by abdominal CT scan to include increases in intra-abdominal adipose tissue.
The aim of this study is to compare the body fat distribution pattern of glibenclamide plus rosiglitazone versus glibenclamide and placebo (especially the intra-abdominal adipose tissue and abdominal subcutaneous adipose tissue areas) in patients with type 2 diabetes. It is hypothesised that rosiglitazone will lead to the accumulation of excess energy stores in the subcutaneous rather than the intra-abdominal adipose tissue depot. In addition, it is hoped that by having a positive effect on diastolic blood pressure, lipid levels, BMI, rosiglitazone will be shown to have a better cardiovascular risk profile when used in combination with glibenclamide rather than when glibenclamide is used alone.
Although insulin resistance has been shown to be a primary defect causing type 2 diabetes mellitus, insulin secretory defect has also been known to be an important factor in the development of type 2 diabetes mellitus. A previous study has shown that in Korean patients, early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes mellitus [56].
This study also aims to assess the efficacy and safety of glibenclamide plus rosiglitazone versus glibenclamide plus placebo therapy in Korean patients with type 2 diabetes. In addition, a previous study has shown that in Korean patients, early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes mellitus. This study aims to show that rosiglitazone treatment in Korean patients, regardless of their early phase insulin secretory ability, is just as efficacious and safe.
Objective(s) Primary To evaluate the effect of 12 months oral treatment with glibenclamide plus rosiglitazone versus oral glibenclamide plus placebo, on body fat distribution (as measured by the change in the ratio between the intra-abdominal adipose tissue and abdominal subcutaneous adipose tissue areas) in patients with type 2 diabetes.
Secondary
- To investigate the efficacy of glibenclamide plus rosiglitazone, compared to glibenclamide plus placebo on beta-cell function and insulin resistance as calculated by HOMA-B and HOMA-R.
- To investigate the efficacy of glibenclamide plus rosiglitazone, compared to glibenclamide plus placebo on fasting plasma glucose, insulin, fasting serum lipid profile (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol to HDL cholesterol ratio).
- To investigate the efficacy of glibenclamide plus rosiglitazone, compared to glibenclamide plus placebo on early phase insulin secretion during an oral glucose tolerance test as measured by the insulinogenic index.
- To define further the clinical safety and tolerability of glibenclamide plus rosiglitazone through the assessment of physical examinations, vital signs, weight, routine laboratory tests, adverse experiences and electrocardiograms (ECGs).
Endpoint(s) Primary Change from baseline in the ratio (IAAT:SAT) between the intra-abdominal adipose tissue area (IAAT) and abdominal subcutaneous adipose tissue area [SAT] after 12 months treatment with oral glibenclamide plus rosiglitazone compared to oral glibenclamide plus placebo Secondary
Comparisons will be made between glibenclamide plus rosiglitazone and glibenclamide plus placebo treatment groups on Change from baseline after 6 and 12 months treatment with respect the following:
CT Scan
Derived from CT image at the lumbar IV level:
- abdominal subcutaneous adipose tissue area [SAT]
- intra-abdominal adipose tissue area [IAAT]
Derived from the CT image of the right leg at the thigh level (1cm below the gluteal fold):
- total subcutaneous adipose tissue area [TSAT] Derived from CT images at the lumbar IV and thigh level
- ratio between abdominal subcutaneous adipose tissue area [SAT] and total subcutaneous adipose tissue area of the thigh [TSAT]
- ratio between intra-abdominal adipose tissue area [IAAT] and total subcutaneous adipose tissue area of the thigh [TSAT] Derived from Oral Glucose Tolerance Test, glycaemic response to OGTT, difference
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| glibenclamide + Rosiglitazone | Active comparator | Drug: titrationglibenclamide plus rosiglitazone |
| glibenclamide + placebo | Placebo comparator | Drug: titration |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| titrationPatients in the glibenclamide plus placebo treatment group Patients in the glibenclamide plus placebo treatment group who have FPG < 270mg/dL after the glibenclamide 5mg om run-in will continue to receive glibenclamide 5mg om. At every subsequent visit, the glibenclamide dose will be titrated to achieve the target HbA1c level of < 7%. If the HbA1c is > 7%, the dose of glibenclamide will be escalated in the following sequence: from 5mg om, to 5mg om, 2.5mg on, to 5mg bd and 7.5mg om, 5mg on, to 7.5mg bd. The maximum total daily dose will not exceed 15 mg. A downward titration of glibenclamide using the above sequence in the reverse order can be used to maintain normoglycemia at any visit. Once the target HbA1c level of < 7% is achieved, the dose of glibenclamide is maintained. If at the glibenclamide dose of 7.5mg bd, the HbA1c is > 7% for 2 subsequent visits, the patient will be withdrawn from the study. | Drug | glibenclamide + placebo |
| titrationPatients in the glibenclamide + rosiglitazone treatment group who have FPG < 270mg/dL after the glibenclamide 5mg om run-in will receive glibenclamide 5mg om + rosiglitazone 4mg om. At every subsequent visit, the glibenclamide dose will be titrated to achieve the target HbA1c level of < 7%. If the HbA1c is > 7%, the dose of glibenclamide will be escalated in a similar fashion as above. The only exception is at visit 5 when the dose of rosiglitazone is increased (see next paragraph). Once the target HbA1c level of < 7% is achieved, the dose of glibenclamide is maintained. If at the glibenclamide dose of 7.5mg bd, the HbA1c is > 7% for 2 subsequent visits, the patient will be withdrawn from the study. | Drug | glibenclamide + Rosiglitazone |
Primary outcome
Change from baseline in the ratio (IAAT:SAT) between the intra-abdominal adipose tissue area (IAAT) and abdominal subcutaneous adipose tissue area [SAT] after 12 months treatment with oral glibenclamide plus rosiglitazone compared to oral glibenclamide p
Time frame: baseline
1 secondary outcome
Comparisons will be made between glibenclamide plus rosiglitazone and glibenclamide plus placebo treatment groups on Change from baseline after 6 and 12 months treatment with respect the following
Time frame: baseline
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 18 Jun 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.
GSK Clinical Trials study director
GlaxoSmithKline
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing titration in people with Diabetes Mellitus, Type 2, run by GlaxoSmithKline at 4 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 18 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in South Korea. 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. 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 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?
Change from baseline in the ratio (IAAT:SAT) between the intra-abdominal adipose tissue area (IAAT) and abdominal subcutaneous adipose tissue area [SAT] after 12 months treatment with oral glibenclamide plus rosiglitazone compared to oral glibenclamide p (time frame: baseline). 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 18 Jun 2012.