Acute Regulation of Intestinal and Hepatic Lipoprotein Production by Glucagon

NCT01155206 | Completed Phase 4

• 1 other identifier: 07-0394-A
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Insulin resistant states are characterized by hepatic lipoprotein (VLDL) particle overproduction. Numerous hormonal and nutritional factors are known to influence hepatic lipoprotein particle production, including insulin and free fatty acids (FFA). In contrast to the liver, the intestine has traditionally been viewed as a 'passive' organ with respect to lipoprotein production, with intestinal lipoprotein particle production determined mainly by the amount of fat ingested and absorbed. Glucagon plays a key role in the regulation of carbohydrate and fatty acid metabolism and has recently been shown for the first time to regulate hepatic lipoprotein production in mice. Ours will be the first study to investigate the effect of glucagon on hepatic and intestinal lipoprotein production in humans.

Conditions

Diabetes

Keywords

glucagon,; high physiological dose and basal dose of glucagon; hepatic lipoprotein production,; free fatty acid; intestinal lipoprotein production; particle; glucagon affects production of fat in intestine and liver.

Outcome Measures

Primary Outcomes (1)

• Triglyceride-rich lipoprotein production rate

  0-10 hours

Study Arms (2)

high glucagon

EXPERIMENTAL

For one of the two studies to be performed in random order, the subject will receive an infusion of glucagon at a dose that has been shown to achieve high physiological plasma levels. The IV glucagon will be administered at a rate of 3ng/kg/min.

Drug: glucagon

low glucagon

EXPERIMENTAL

For one of the two studies to be performed in random order, the subject will receive an infusion of glucagon at a low rate that is designed to mimic basal plasma glucagon concentration. The IV glucagon will be administered at a rate of 0.65ng/kg/min.

Drug: glucagon

Interventions

glucagon DRUG

glucagon 3ng/kg/min

Also known as: glucagon 0.65ng/kg/min

high glucagon; low glucagon

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women, aged 18 to 40 years
• Body mass index 20 kg/m2 to 25 kg/m2
• Hemoglobin above 130g/L.
• Normal glucose tolerance in response to a 75g, 2-hr OGTT

You may not qualify if:

• Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.
• Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr \> 1.5 mg/dL), genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP \> 100 or systolic \> 180) or proliferative retinopathy
• Fasting blood glucose \> 6.0 mmol/l or known diabetes.
• Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure.
• Any laboratory values: AST \> 2x ULN; ALT \> 2x ULN TSH \> 6 mU/l
• Current addiction to alcohol or substances of abuse as determined by the investigator.
• Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
• Taking any prescription or non-prescription medications at the time of the study
• Having donated blood three months prior to and three months post study procedures
• A pregnancy test will be performed 1 to 3 days prior to each study in all female subjects. Those who test positive for pregnancy will be excluded.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network, Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Glucagon

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Gary F Lewis, MD

  University Health Network, Toronto General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 25, 2008
• First Posted: July 1, 2010
• Study Start: June 1, 2009
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: December 2, 2015

Record last verified: 2007-09

Locations

CA (1)