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

Phase 2

Completed

• Conditions: Healthy
• Interventions: Biological: glucose or normal saline

• Registration Number: NCT02607839
• Lead Sponsor: University Health Network, Toronto

Brief Summary

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.

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 Timeline

• Study Start: 2013-02
• Primary Completion: 2015-04
• Study Completion: 2015-09
• Status Verified: 2015-11
• Study First Submitted: 2015-11-16
• Study First Submitted QC: 2015-11-17
• Last Update Submitted: 2015-11-17
• Study First Posted: 2015-11-18
• Last Update Posted: 2015-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
normal saline	glucose or normal saline	normal saline intravenous infusion
glucose	glucose or normal saline	glucose intravenous infusion

Primary Outcome Measures

Name	Time	Method
Production of TRL-apoB48 between treatments	10 hours

Secondary Outcome Measures

Name	Time	Method
Production of TRL-apoB100 between treatments	10 hours

Trial Locations

Locations (1)

Tornto General Hospital, UHN; 🇨🇦 Toronto, Ontario, Canada