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

NCT00738023 | Completed Phase 4 Results DMC

• 1 other identifier: 967-2003
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Type 2 Diabetes; Hypertension

Keywords

diabetes,; hypertension,; free-fatty acids

Outcome Measures

Primary Outcomes (1)

• Changes in Systolic Blood Pressure During Initial Intralipid Infusion

  Systolic blood pressure change from baseline during an 48-hour intralipid infusion

  Baseline, 48 hours

Secondary Outcomes (2)

• Changes in Systolic Blood Pressure During Saline Infusions

  48 hours

• Changes in Systolic Blood Pressure During Intralipid Infusion Post-rosiglitazone Intervention

  48 hours

Study Arms (2)

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

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

Drug: Intralipid 20%

Interventions

Rosiglitazone DRUG

Diabetic subjects will be receive rosiglitazone for 6 weeks

Diabetics

Normal saline 0.9% DRUG

Normal saline 0.9% intravenous infusion at 40ml/hr for 48 hours

Diabetics

Intralipid 20% DRUG

Intralipid 20% at 40ml/hr intravenously for 48 hours

Diabetics; Non-Diabetic

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertension; Diabetes Mellitus

Interventions

Rosiglitazone; Saline Solution

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Guillermo Umpierrez
• Organization: Emory University

geumpie@emory.edu

404-778-1665

Study Officials

• Guillermo Umpierrez, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 19, 2008
• First Posted: August 20, 2008
• Study Start: March 1, 2004
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: December 30, 2014
• Results First Posted: December 30, 2014

Record last verified: 2014-12

Locations

US (1)