Determining the Responsiveness of Intestinal Lipoprotein Production to an Elevation of Plasma Free Fatty Acids

NCT00152945 | Completed

• 2 other identifiers: 04-0575-BCIHR Grant 777509574
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Lipoproteins are large complexes of molecules that transport lipids (primarily triglycerides and cholesterol) through the blood. The intestine has traditionally been viewed as a 'passive' organ with respect to lipoprotein production, with intestinal lipoprotein production rates responding mainly to fat ingestion and absorption. The investigators have recently demonstrated in animal models that there is an overproduction of intestinal lipoproteins in both the fasted and the fed state. The investigators have also recently demonstrated that an elevation of plasma free fatty acids (FFAs) stimulates intestinal lipoprotein in hamsters. It is not known whether intestinal lipoprotein production can be acutely stimulated by an elevation of plasma FFAs in humans. Hypothesis: Intestinal lipoprotein particle production in humans can be stimulated by an acute elevation of plasma free fatty acids.

Conditions

Insulin Resistance

Keywords

intestinal lipoprotein; very low density lipoprotein; free fatty acids; Apo B48 and Apo B100; triglycerides; Intestinal lipoprotein production

Outcome Measures

Primary Outcomes (1)

• To determine if the elevation of plasma FFAs by infusing intralipid and heparin stimulates intestinal lipoprotein production

  blood samples at 1,2,3,5,7,9,10,11 and 12 hours

Interventions

Intravenous Intralipid DRUG

intravenous infusion

Intravenous leucine, glycerol DRUG

intravenous infusion

Eligibility Criteria

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

You may qualify if:

• Non-diabetic men and women aged 18-65 years old
• Written informed consent obtained
• Body mass index (BMI) \< 27 kg/m2
• Fasting triglycerides \< 2.5 mmol/l
• Waist circumference \< 90 cm
• Fasting blood glucose \< 6 mmol/l
• Haemoglobin above 130 g/L.

You may not qualify if:

• Patient has a history of hepatitis/hepatic disease that has been active within the previous 2 years.
• Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (creatinine \[Cr\] \> 1.5 mg/dL) genitourinary, or hematological systems; or severe uncontrolled treated or untreated hypertension (sitting diastolic blood pressure \[BP\] \> 100 or systolic \> 180); or proliferative retinopathy.
• Fasting blood glucose \> 6 mmol/l or known diabetes.
• Any history of a myocardial infarction (MI) or clinically significant, active, cardiovascular history including a history of arrhythmias or conduction delays on electrocardiogram (ECG), unstable angina, or decompensated heart failure.
• Any laboratory values: AST \> 2x upper limit of normal (ULN); ALT \> 2x ULN; thyroid-stimulating hormone (TSH) \> 6 mU/l.
• Known or suspected allergy to the medication or a history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions.
• Current addiction to alcohol or substances of abuse as determined by the investigator.
• Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
• Any lipid lowering or hypoglycemic agents
• Will not donate blood three months before start or three months after completing study.
• Thrombocytopenia

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2c4, Canada

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Glycerol

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Triose Sugar Alcohols; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Gary F Lewis, MD

  University Health Network, Toronto, Ontario, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Medicine and Physiology

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 9, 2005
• Study Start: April 1, 2005
• Primary Completion: July 1, 2008
• Study Completion: October 1, 2008
• Last Updated: October 2, 2012

Record last verified: 2012-09

Locations

CA (1)