Type 2 DiabetesPhase 4NCT00738023
Free Fatty Acid-Induced Hypertension in Obese Subjects With Type 2 Diabetes
A Phase 4 study testing Rosiglitazone, Normal saline 0.9% and Intralipid 20% in people with Type 2 Diabetes and Hypertension, run by Emory University at 1 site in United States.
Trial summary
Insulin resistance has been implicated as the central pathogenetic feature of cardiovascular risk factor cluster that includes hypertension, impaired glucose tolerance, diabetes, dyslipidemia, and hemostatic disorders. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes, Hypertension
- What is being tested?
- Rosiglitazone, Normal saline 0.9% and Intralipid 20%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2004to Dec 2009
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males or females between the ages of 18 and 70 years.
- Subjects must have a BMI of ≥ 30 kg/m2.
- Subjects must have a BP < 130/80 mm Hg and no prior history of hypertension.
- A known history of type 2 diabetes mellitus < 3 years (now 5 years).
- Subjects must have an HbA1c of < 9%.
- Diabetic subjects must have been receiving as their only current anti-diabetic therapy stable doses of sulfonylureas for the last 2 months.
- Subjects must be able to understand and willing to adhere to the study protocol.
Who cannot join
- Subjects with history of hypertension (BP > 140/90 mm HG) or who have received antihypertensive drug therapy prior to the study.
- Obese nondiabetic controls with impaired glucose tolerance (2-hour glucose between 140 - 199 mg/dl) during a 75-g OGTT.
- Diabetic subjects who require insulin therapy or have received an insulin sensitizer agent (metformin, rosiglitazone, pioglitazone) within 3 months of entering the study (at SV1, week-2).
- Subjects with fasting triglyceride levels > 250 mg/dL prior to the study (at SV1, week-2).
- Clinically relevant hepatic disease (ALT 2.5x > upper limit of normal), or other significant medical or surgical illness.
- Renal failure, as shown by a serum creatinine ≥1.5 mg/dL for males, or ≥ 1.4 mg/dL for females.
- Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
- Female subjects are pregnant or breast feeding at time of enrollment into the study.
Trial locations and contacts
1 site in 1 country.
About this study
Insulin resistance has been implicated as the central pathogenetic feature of cardiovascular risk factor cluster that includes hypertension, impaired glucose tolerance, diabetes, dyslipidemia, and hemostatic disorders. Recent evidence suggests that increased levels of free fatty acids (FFA) in obese subjects is a leading candidate in the pathogenesis of insulin resistance (1-4). In our preliminary studies on the effect of FFA on insulin secretion and action (lipotoxicity), we have observed that the infusion of Intralipid/heparin to increase FFA ~ four-fold-baseline levels for 48 hours results in a significant and reproducible raise in systolic and diastolic blood pressure (BP) in obese African American subjects with and without diabetes. The increase in blood pressure is apparent after 12 hours of infusion, reaching a peak increment of 32 mm Hg in systolic and 14 mm Hg in diastolic pressure at 24 hours. These preliminary findings indicate that, in addition to the well-known effect on insulin resistance, sustained elevation of FFA results in the development of an acute metabolic syndrome.
Read the detailed description
The FFA-induced hypertension constitutes a useful model with which to examine disease mechanisms and test new therapeutic interventions to correct the different disorders associated with insulin resistance and metabolic syndrome. The effect of FFA on insulin action is well established (4-6); however, the pressor effect of FFA infusion in obese subjects has not been investigated. We hypothesize that observed changes in blood pressure is the result of acute endothelial dysfunction due to increased FFA concentration; and that rosiglitazone, a PPAR gamma receptor agonist, will protect against FFA-induced elevation in blood pressure and endothelial dysfunction in obese subjects.
- Conditions
- Type 2 Diabetes, Hypertension
- Being tested
- Rosiglitazone, Normal saline 0.9%, Intralipid 20%
- Keywords
- diabetes,, hypertension,, free-fatty acids
- Medical subject headings
- Diabetes Mellitus, Type 2, Hypertension, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RosiglitazoneDrug
Diabetic subjects will be receive rosiglitazone for 6 weeks
Normal saline 0.9%Drug
Normal saline 0.9% intravenous infusion at 40ml/hr for 48 hours
Intralipid 20%Drug
Intralipid 20% at 40ml/hr intravenously for 48 hours
| Study group | Role | What they receive |
|---|---|---|
| Diabetics | Active comparator | Obese, normotensive African-Americans with diabetes received Intralipid 20% at 40ml/hr intravenously for 48 hours, then normal saline 0.9% at 40 ml/hr intravenously for 48 hours, and then randomized to rosiglitazone for six weeks followed by Intralipid 20% at 40ml/hr intravenously for 48 hours Receives: Drug: Rosiglitazone; Drug: Normal saline 0.9%; Drug: Intralipid 20% |
| Non-Diabetic | Active comparator | Obese, normotensive African-Americans without diabetes received Intralipid 20% at 40ml/hr intravenously for 48 hours Receives: Drug: Intralipid 20% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Systolic Blood Pressure During Initial Intralipid Infusion
Systolic blood pressure change from baseline during an 48-hour intralipid infusion
Measured: Baseline, 48 hours
Secondary outcomes (2)
Changes in Systolic Blood Pressure During Saline Infusions
Systolic blood pressure change from baseline during an 48-hour normal saline infusion in obese diabetic subjects
Measured: 48 hours
Changes in Systolic Blood Pressure During Intralipid Infusion Post-rosiglitazone Intervention
Systolic blood pressure change from baseline during an 48-hour intralipid infusion after taking rosiglitazone for 6 weeks in obese diabetic subjects
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2008 (estimated)
- Study startMar 2004
- Primary completionDec 2009
- Study completionDec 2009
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.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Guillermo Umpierrez, Emory University
- Investigators
- Guillermo Umpierrez, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00738023
- Sponsor's protocol ID
- 967-2003
- Status last verified
- Dec 2014
- First submitted
- 19 Aug 2008
- Last updated
- 30 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Free Fatty Acid-Induced Hypertension in Obese Subjects With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT00738023
- Acronym / sponsor ID
- 967-2003
- Conditions
- Type 2 Diabetes, Hypertension
- Keywords
- diabetes,, hypertension,, free-fatty acids
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Mar 2004
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 20 Aug 2008 (estimated)
- Results
- Posted 30 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Insulin resistance has been implicated as the central pathogenetic feature of cardiovascular risk factor cluster that includes hypertension, impaired glucose tolerance, diabetes, dyslipidemia, and hemostatic disorders. Recent evidence suggests that increased levels of free fatty acids (FFA) in obese subjects is a leading candidate in the pathogenesis of insulin resistance (1-4). In our preliminary studies on the effect of FFA on insulin secretion and action (lipotoxicity), we have observed that the infusion of Intralipid/heparin to increase FFA ~ four-fold-baseline levels for 48 hours results in a significant and reproducible raise in systolic and diastolic blood pressure (BP) in obese African American subjects with and without diabetes. The increase in blood pressure is apparent after 12 hours of infusion, reaching a peak increment of 32 mm Hg in systolic and 14 mm Hg in diastolic pressure at 24 hours. These preliminary findings indicate that, in addition to the well-known effect on insulin resistance, sustained elevation of FFA results in the development of an acute metabolic syndrome.
Detailed description
The FFA-induced hypertension constitutes a useful model with which to examine disease mechanisms and test new therapeutic interventions to correct the different disorders associated with insulin resistance and metabolic syndrome. The effect of FFA on insulin action is well established (4-6); however, the pressor effect of FFA infusion in obese subjects has not been investigated. We hypothesize that observed changes in blood pressure is the result of acute endothelial dysfunction due to increased FFA concentration; and that rosiglitazone, a PPAR gamma receptor agonist, will protect against FFA-induced elevation in blood pressure and endothelial dysfunction in obese subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diabetics | Active comparator | Drug: Rosiglitazone, Drug: Normal saline 0.9%, Drug: Intralipid 20%Obese, normotensive African-Americans with diabetes received Intralipid 20% at 40ml/hr intravenously for 48 hours, then normal saline 0.9% at 40 ml/hr intravenously for 48 hours, and then randomized to rosiglitazone for six weeks followed by Intralipid 20% at 40ml/hr intravenously for 48 hours |
| Non-Diabetic | Active comparator | Drug: Intralipid 20%Obese, normotensive African-Americans without diabetes received Intralipid 20% at 40ml/hr intravenously for 48 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Males or females between the ages of 18 and 70 years.
- Subjects must have a BMI of ≥ 30 kg/m2.
- Subjects must have a BP < 130/80 mm Hg and no prior history of hypertension.
- A known history of type 2 diabetes mellitus < 3 years (now 5 years).
- Subjects must have an HbA1c of < 9%.
Key exclusion criteria (8 listed)
- Subjects with history of hypertension (BP > 140/90 mm HG) or who have received antihypertensive drug therapy prior to the study.
- Obese nondiabetic controls with impaired glucose tolerance (2-hour glucose between 140 - 199 mg/dl) during a 75-g OGTT.
- Diabetic subjects who require insulin therapy or have received an insulin sensitizer agent (metformin, rosiglitazone, pioglitazone) within 3 months of entering the study (at SV1, week-2).
- Subjects with fasting triglyceride levels > 250 mg/dL prior to the study (at SV1, week-2).
- Clinically relevant hepatic disease (ALT 2.5x > upper limit of normal), or other significant medical or surgical illness.
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 |
|---|---|---|
| RosiglitazoneDiabetic subjects will be receive rosiglitazone for 6 weeks | Drug | Diabetics |
| Normal saline 0.9%Normal saline 0.9% intravenous infusion at 40ml/hr for 48 hours | Drug | Diabetics |
| Intralipid 20%Intralipid 20% at 40ml/hr intravenously for 48 hours | Drug | Diabetics, Non-Diabetic |
Primary outcome
Changes in Systolic Blood Pressure During Initial Intralipid Infusion
Time frame: Baseline, 48 hours
Systolic blood pressure change from baseline during an 48-hour intralipid infusion
2 secondary outcomes
Changes in Systolic Blood Pressure During Saline Infusions
Time frame: 48 hours
Changes in Systolic Blood Pressure During Intralipid Infusion Post-rosiglitazone Intervention
Time frame: 48 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Guillermo Umpierrez, MD principal investigator
Emory University
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 Rosiglitazone, Normal saline 0.9% and Intralipid 20% in people with Type 2 Diabetes and Hypertension, run by Emory University 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 7 inclusion and 8 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 30 Dec 2014. 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 30 Dec 2014). 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?
Changes in Systolic Blood Pressure During Initial Intralipid Infusion (time frame: Baseline, 48 hours). 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 30 Dec 2014.