Regulation of Intestinal and Hepatic Lipoprotein Particle Production by Blood Glucose in Humans

The purpose of study is to examine whether raised blood glucose enhances lipid particle production independent of effects on gastric emptying and pancreatic/ gastrointestinal hormone production.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: glucose or normal saline

Detailed Description

This study will be performed on healthy, lean, non-diabetic males and females who will participate two studies each in random order, 4 to 6 weeks apart. Study A: lipoprotein turnover with intravenous infusion of normal saline. Study B: lipoprotein turnover i.v infusion of glucose. In both studies, subjects will drink a liquid formula every hour to remain in a constant fed state and will be under conditions of pancreatic clamp (with the infusion of hormones somatostatin, insulin, glucagon, growth hormone). Subjects will be blinded with regard to the treatments.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1L7
      • Tornto General Hospital, UHN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women, aged 18 to 60 years
2. Body mass index 20 kg/m2 to 27 kg/m2
3. Hemoglobin above 130g/L
4. Normal glucose tolerance in response to a 75g, 2-hr OGTT

Exclusion Criteria:

1. Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.
2. Any subject with active bleeding, bleeding diathesis, clotting abnormalities or recent surgery (within past 1 month)
3. 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).
4. History of diabetes or OGTT indicative of diabetes or impaired glucose tolerance.
5. 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.
6. Any laboratory values: AST > 2x ULN; ALT > 2x ULN TSH > 6 mU/l
7. Current addiction to alcohol or substances of abuse as determined by the investigator.
8. Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
9. Taking any prescription or non-prescription medications at the time of the study
10. Having donated blood three months prior to and three months post study procedures
11. 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.
12. Known allergy, hypersensitivity or contraindication to receiving study medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: normal saline; normal saline intravenous infusion	Biological: glucose or normal saline; 20% glucose solution or normal saline, intravenous infusion
Active Comparator: glucose; glucose intravenous infusion	Biological: glucose or normal saline; 20% glucose solution or normal saline, intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Production of TRL-apoB48 between treatments	10 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Production of TRL-apoB100 between treatments	10 hours

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Publications and helpful links

General Publications

• Xiao C, Dash S, Morgantini C, Lewis GF. Intravenous Glucose Acutely Stimulates Intestinal Lipoprotein Secretion in Healthy Humans. Arterioscler Thromb Vasc Biol. 2016 Jul;36(7):1457-63. doi: 10.1161/ATVBAHA.115.307044. Epub 2016 May 5.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: November 16, 2015
• First Submitted That Met QC Criteria: November 17, 2015
• First Posted (Estimate): November 18, 2015

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: November 17, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: lipid handling by the gut and liver
• Other Study ID Numbers: 12-5569-B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No