Diabetes MellitusPhase 3NCT00203632
Glitazones and Endothelial Function (GATE)
A Phase 3 study of Diabetes Mellitus, run by University of Calgary at 1 site in Canada.
Trial summary
The purpose of the study is to determine if the addition of rosiglitazone to subjects with fair glucose control on other oral agents improves endothelial function, a surrogate marker of vascular health. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2003to Oct 2007
- Phase
- Phase 3
- 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
- All patients (both men and women) considered for participation in GATE study have to be non-insulin dependent diabetics (according to Canadian Diabetes Association criteria, namely a fasting serum glucose ≥ 7.0 mmol/L on two occasions, a casual glucose ≥ 11.1 mmol/l with symptoms, or a 2-h post-oral glucose tolerance test glucose of ≥ 11.1 mmol/l) with unsatisfactory glycemic control on oral therapy (HbA1c 6-10%).
Who cannot join
- Exclusion criteria includes, congestive heart failure (NYHA class III \& IV or ejection fraction less than 35%), poorly controlled hypertension (blood pressure > 160/90), hypercholesterolemia (total cholesterol > 6.2 mmol/l), hypertriglyceridemia (triglycerides > 4.0 mmol/l), poor or excellent control of DM (HgA1c <6 % or HbA1c > 10% respectively), known diabetic retinopathy, age at diagnosis of diabetes less than 25 years, current participation in another clinical trial and contraindications to glitazones therapy, including renal (creatinine > 200 micromol/ L) or hepatic (ALT > 2.5 times the upper limit of normal) impairment and/ or known intolerance to glitazones. Patients must be stable on medications that affect endothelial function for more than one month. This includes ACE-inhibitors, angiotensin receptor blockers, statins, calcium channel blockers, hormone replacement therapy and anti-oxidant vitamins, including folates. Patients on insulin will be excluded. Patients in whom it is felt that attainment of better glucose control is required within 3 months will also be excluded. Patients with stable coronary disease will be eligible for the study as long as they are > one month post myocardial infarction, percutaneous intervention or bypass surgery.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Trial of the Effect of Rosiglitazone as Add on to Metformin Therapy on Endothelial Function in Subjects With Type II DM
The purpose of the study is to determine if the addition of rosiglitazone to subjects with fair glucose control on other oral agents improves endothelial function, a surrogate marker of vascular health.
It is hypothesized that improving whole body insulin sensitivity with combination therapy including rosiglitazone will restore the vascular actions of insulin and improve endothelium-dependent vasomotion more effectively than placebo in patients with diabetes mellitus.
Read the detailed description
The vascular endothelium has emerged as a critical determinant of cardiovascular health and disease, and improving endothelial function is an important target for therapy. Accumulating evidence suggest that insulin resistance in patients with diabetes and the metabolic syndrome may impair endothelial function, uncovering a proinflammatory, and proatherosclerotic vascular phenotype. The GATE study (Glitazones And The Endothelium) is a randomized, double blind study to evaluate the effects of rosiglitazone vs. placebo on endothelial function when employed as an add-on therapy in diabetic patients currently treated with oral therapy. We hypothesize that the PPAR-gamma agonist rosiglitazone, will improve endothelium-dependent vasodilatation, and that this effect will be related to improvements in insulin sensitivity, with concomitant reductions in whole body insulin resistance. Furthermore, the beneficial effects of rosiglitazone will be additive to existing oral therapies that may modulate endothelial function, such as metformin. Since endothelial dysfunction plays a pivotal role in the development and progression of atherosclerosis, these studies may provide the rationale and impetus for aggressive treatment of insulin resistant patients with glitazone therapy.
- Conditions
- Diabetes Mellitus
- Being tested
- rosiglitazone/placebo
- Keywords
- diabetes mellitus, endothelium, thiazolidinediones, atherosclerosis
- Medical subject headings
- Diabetes Mellitus, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rosiglitazone/placeboDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary end-point of the study is the percent change in forearm blood flow to acetylcholine in patients randomized to rosiglitazone compared with placebo.
Secondary outcomes (1)
Secondary end-points include (i) the percent change in forearm blood flow to verapamil and the absolute change to both acetylcholine and verapamil and (ii) the relationship between HOMA-IR, CRP and endothelial function.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startSep 2003
- Study completionOct 2007
Why it stopped: Terminated at 50% enrollment due to recent concerns about rosiglitazone
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Investigators
- Todd J Anderson, MD, Principal investigator, University of CalgarySubodh Verma, MD, PhD, Study chair, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00203632
- Sponsor's protocol ID
- TPD 084385
- Status last verified
- Oct 2008
- First submitted
- 13 Sep 2005
- Last updated
- 3 Nov 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hubacek J, Verma S, Shewchuk L, Ross SJ, Edwards A, Anderson TJ. Rationale and design of the Glitazones and the Endothelium (GATE) study: evaluation of rosiglitazone on endothelial function in patients with diabetes. Can J Cardiol. 2004 Dec;20(14):1449-53.
PubMed 15614340
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of the Effect of Rosiglitazone as Add on to Metformin Therapy on Endothelial Function in Subjects With Type II DM
- ClinicalTrials.gov ID
- NCT00203632
- Acronym / sponsor ID
- TPD 084385
- Conditions
- Diabetes Mellitus
- Keywords
- diabetes mellitus, endothelium, thiazolidinediones, atherosclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated at 50% enrollment due to recent concerns about rosiglitazone
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Sep 2003
- Study completion
- Oct 2007 (actual)
- First posted
- 20 Sep 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.
The purpose of the study is to determine if the addition of rosiglitazone to subjects with fair glucose control on other oral agents improves endothelial function, a surrogate marker of vascular health.
It is hypothesized that improving whole body insulin sensitivity with combination therapy including rosiglitazone will restore the vascular actions of insulin and improve endothelium-dependent vasomotion more effectively than placebo in patients with diabetes mellitus.
Detailed description
The vascular endothelium has emerged as a critical determinant of cardiovascular health and disease, and improving endothelial function is an important target for therapy. Accumulating evidence suggest that insulin resistance in patients with diabetes and the metabolic syndrome may impair endothelial function, uncovering a proinflammatory, and proatherosclerotic vascular phenotype. The GATE study (Glitazones And The Endothelium) is a randomized, double blind study to evaluate the effects of rosiglitazone vs. placebo on endothelial function when employed as an add-on therapy in diabetic patients currently treated with oral therapy. We hypothesize that the PPAR-gamma agonist rosiglitazone, will improve endothelium-dependent vasodilatation, and that this effect will be related to improvements in insulin sensitivity, with concomitant reductions in whole body insulin resistance. Furthermore, the beneficial effects of rosiglitazone will be additive to existing oral therapies that may modulate endothelial function, such as metformin. Since endothelial dysfunction plays a pivotal role in the development and progression of atherosclerosis, these studies may provide the rationale and impetus for aggressive treatment of insulin resistant patients with glitazone therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients (both men and women) considered for participation in GATE study have to be non-insulin dependent diabetics (according to Canadian Diabetes Association criteria, namely a fasting serum glucose ≥ 7.0 mmol/L on two occasions, a casual glucose ≥ 11.1 mmol/l with symptoms, or a 2-h post-oral glucose tolerance test glucose of ≥ 11.1 mmol/l) with unsatisfactory glycemic control on oral therapy (HbA1c 6-10%).
Key exclusion criteria (1 listed)
- Exclusion criteria includes, congestive heart failure (NYHA class III \& IV or ejection fraction less than 35%), poorly controlled hypertension (blood pressure > 160/90), hypercholesterolemia (total cholesterol > 6.2 mmol/l), hypertriglyceridemia (triglycerides > 4.0 mmol/l), poor or excellent control of DM (HgA1c <6 % or HbA1c > 10% respectively), known diabetic retinopathy, age at diagnosis of diabetes less than 25 years, current participation in another clinical trial and contraindications to glitazones therapy, including renal (creatinine > 200 micromol/ L) or hepatic (ALT > 2.5 times the upper limit of normal) impairment and/ or known intolerance to glitazones. Patients must be stable on medications that affect endothelial function for more than one month. This includes ACE-inhibitors, angiotensin receptor blockers, statins, calcium channel blockers, hormone replacement therapy and anti-oxidant vitamins, including folates. Patients on insulin will be excluded. Patients in whom it is felt that attainment of better glucose control is required within 3 months will also be excluded. Patients with stable coronary disease will be eligible for the study as long as they are > one month post myocardial infarction, percutaneous intervention or bypass surgery.
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 |
|---|---|---|
| rosiglitazone/placebo | Drug | – |
Primary outcome
The primary end-point of the study is the percent change in forearm blood flow to acetylcholine in patients randomized to rosiglitazone compared with placebo.
1 secondary outcome
Secondary end-points include (i) the percent change in forearm blood flow to verapamil and the absolute change to both acetylcholine and verapamil and (ii) the relationship between HOMA-IR, CRP and endothelial function.
Results and safety
The study was stopped early (reason given: Terminated at 50% enrollment due to recent concerns about rosiglitazone). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2008.
- Background: PubMed 15614340Hubacek J, Verma S, Shewchuk L, Ross SJ, Edwards A, Anderson TJ. Rationale and design of the Glitazones and the Endothelium (GATE) study: evaluation of rosiglitazone on endothelial function in patients with diabetes. Can J Cardiol. 2004 Dec;20(14):1449-53.
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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.
Todd J Anderson, MD principal investigator
University of Calgary
Subodh Verma, MD, PhD study chair
University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study of Diabetes Mellitus, run by University of Calgary at 1 site in Canada.
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 1 inclusion and 1 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: stopped early, as of the sponsor's last update on 3 Nov 2008. 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 Canada. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 stopped early (reason given: Terminated at 50% enrollment due to recent concerns about rosiglitazone). 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 primary end-point of the study is the percent change in forearm blood flow to acetylcholine in patients randomized to rosiglitazone compared with placebo.. 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 NCT00203632, 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 3 Nov 2008.