Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Free Fatty Acid-Induced Hypertension in Obese Subjects With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Guillermo Umpierrez, Emory University
ClinicalTrials.gov Identifier:
NCT00738023
First received: August 19, 2008
Last updated: June 7, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes
Hypertension
Drug: Rosiglitazone
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Free Fatty Acid-Induced Hypertension in Obese Subjects With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • To determine the effects of sustained elevations of FFA on blood pressure and endothelial function in obese normotensive subjects. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine whether rosiglitazone could protect against FFA-induced insulin resistance, increased blood pressure, and endothelial dysfunction in obese normotensive subjects with type 2 diabetes. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: March 2004
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Intralipid 20% at 40ml/hr received intravenously for 48 hours
Drug: Rosiglitazone
Diabetic subjects will be receive rosiglitazone for 6 weeks
Placebo Comparator: 2
Normal saline 0.9% intravenous infusion at 40ml/hr for 48 hours
Drug: Placebo
Diabetic subjects will be receive placebo for 6 weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00738023

Locations
United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
GlaxoSmithKline
Investigators
Principal Investigator: Guillermo Umpierrez, MD Emory University
  More Information

No publications provided

Responsible Party: Guillermo Umpierrez, Professor, Emory University
ClinicalTrials.gov Identifier: NCT00738023     History of Changes
Other Study ID Numbers: 967-2003
Study First Received: August 19, 2008
Last Updated: June 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
diabetes,
hypertension,
free-fatty acids

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vascular Diseases
Rosiglitazone
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014