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The Effect of Intranasal Insulin on Hepatic and Intestinal Triglyceride-rich Lipoprotein Production (LPNI)

Primary Purpose

Hyperlipidemia

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Insulin

Placebo

About this trial

This is an interventional basic science trial for Hyperlipidemia focused on measuring Lipoprotein, Apolipoprotein, Pancreatic clamp, Insulin, Nasal

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Men and women, aged 18 to 60 years
Body mass index 20 to 40 kg/m2
Hemoglobin in the normal range.
Normal glucose tolerance in response to a 75g, 2-hr oral glucose tolerance test
Women of reproductive age should be on contraception (oral contraceptive pill or intra-uterine device/coil) for at least 2 months prior to and after the study.

Exclusion Criteria:

Study participant with a history of hepatitis/hepatic disease that has been active within the previous two years.
Any current or previous history of biliary disease (including gall stones, biliary atresia and cholecystitis) or pancreatitis.
Any current or previous history of endocrine disease, dyslipidemia or malignancy
Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (creatinine > 1.5 mg/dL) genitourinary, hematological systems, or has severe uncontrolled treated or untreated hyper/ hypotension (sitting diastolic pressure > 100 or systolic > 180 or systolic pressure <100) or proliferative retinopathy
Use of immunosuppressive agents at any time during the study
Allergy to any study medication
Pregnancy or breastfeeding
Heavy smoker
Fasting blood glucose > 6.0 mmol/l or known diabetes.
Any history of a myocardial infarction or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on electrocardiogram, unstable angina, or decompensated heart failure.
Any nasal pathology.
Any laboratory values: aspartate aminotransferase > 2x upper limit of normal ; alanine aminotransferase > 2x upper limit of normal; thyroid-stimulating hormone > 6 milliunit per litre

Sites / Locations

Tornto General Hospital, UHN

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Insulin

Placebo

Arm Description

Nasal spray, insulin 40 IU, single dose

Nasal spray, placebo, single dose

Outcomes

Primary Outcome Measures

Triglyceride-rich lipoprotein apolipoprotein B100 production rate

Triglyceride-rich lipoprotein apolipoprotein B100 production rate will be measured following nasal spray of insulin or placebo

Secondary Outcome Measures

Triglyceride-rich lipoprotein apolipoprotein B48 production rate

Triglyceride-rich lipoprotein apolipoprotein B48 production rate will be measured following nasal spray of insulin or placebo

Full Information

NCT ID

NCT03141827

First Posted

May 3, 2017

Last Updated

May 4, 2017

Sponsor

University Health Network, Toronto

1. Study Identification

Unique Protocol Identification Number

NCT03141827

Brief Title

The Effect of Intranasal Insulin on Hepatic and Intestinal Triglyceride-rich Lipoprotein Production

Acronym

LPNI

Official Title

The Effect of Intranasal Insulin on Hepatic and Intestinal Triglyceride-rich Lipoprotein Production

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

April 14, 2016 (Actual)

Primary Completion Date

February 15, 2017 (Actual)

Study Completion Date

April 26, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Health Network, Toronto

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study compares the effect of insulin given as a nasal spray with a placebo. Insulin is a chemical messenger (hormone) in the body that controls fat (triglyceride) levels in the blood by controlling the amount of fat made by the liver and gut. Recent research suggests that insulin may work through the brain. The investigators hypothesize that preferential delivery of insulin into the brain, through nasal spray of the hormone, may affect the amount of fats made by the liver and gut.

Detailed Description

Each subject will be studied twice 4-6 weeks apart in random order in this single blinded study. In study A they will receive a single dose of insulin 40 IU through nasal spray. In study B they will receive placebo. On the day of the study subjects will drink regular liquid nutrient formula to maintain a constant fed state. A pancreatic clamp (octreotide with replacement glucose, insulin and growth hormone) will be started at 7am. From 9am a regular infusion of a stable isotope tracer will be started together with nasal spray of either insulin/placebo. Regular blood samples will be drawn to assess lipoprotein kinetics.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyperlipidemia

Keywords

Lipoprotein, Apolipoprotein, Pancreatic clamp, Insulin, Nasal

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2, Phase 3

Interventional Study Model

Crossover Assignment

Masking

Participant

Allocation

Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Insulin

Arm Type

Experimental

Arm Description

Nasal spray, insulin 40 IU, single dose

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Nasal spray, placebo, single dose

Intervention Type

Drug

Intervention Name(s)

Insulin

Intervention Description

Insulin 40 IU, nasal spray, single dose

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo, nasal spray, single dose

Primary Outcome Measure Information:

Title

Triglyceride-rich lipoprotein apolipoprotein B100 production rate

Description

Triglyceride-rich lipoprotein apolipoprotein B100 production rate will be measured following nasal spray of insulin or placebo

Time Frame

10 hours

Secondary Outcome Measure Information:

Title

Triglyceride-rich lipoprotein apolipoprotein B48 production rate

Description

Triglyceride-rich lipoprotein apolipoprotein B48 production rate will be measured following nasal spray of insulin or placebo

Time Frame

10 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men and women, aged 18 to 60 years Body mass index 20 to 40 kg/m2 Hemoglobin in the normal range. Normal glucose tolerance in response to a 75g, 2-hr oral glucose tolerance test Women of reproductive age should be on contraception (oral contraceptive pill or intra-uterine device/coil) for at least 2 months prior to and after the study. Exclusion Criteria: Study participant with a history of hepatitis/hepatic disease that has been active within the previous two years. Any current or previous history of biliary disease (including gall stones, biliary atresia and cholecystitis) or pancreatitis. Any current or previous history of endocrine disease, dyslipidemia or malignancy Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (creatinine > 1.5 mg/dL) genitourinary, hematological systems, or has severe uncontrolled treated or untreated hyper/ hypotension (sitting diastolic pressure > 100 or systolic > 180 or systolic pressure <100) or proliferative retinopathy Use of immunosuppressive agents at any time during the study Allergy to any study medication Pregnancy or breastfeeding Heavy smoker Fasting blood glucose > 6.0 mmol/l or known diabetes. Any history of a myocardial infarction or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on electrocardiogram, unstable angina, or decompensated heart failure. Any nasal pathology. Any laboratory values: aspartate aminotransferase > 2x upper limit of normal ; alanine aminotransferase > 2x upper limit of normal; thyroid-stimulating hormone > 6 milliunit per litre

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gary F Lewis, MD

Organizational Affiliation

University Health Network, Toronto

Official's Role

Principal Investigator

Facility Information:

Facility Name

Tornto General Hospital, UHN

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1L7

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

28751575

Citation

Xiao C, Dash S, Stahel P, Lewis GF. Effects of Intranasal Insulin on Triglyceride-Rich Lipoprotein Particle Production in Healthy Men. Arterioscler Thromb Vasc Biol. 2017 Sep;37(9):1776-1781. doi: 10.1161/ATVBAHA.117.309705. Epub 2017 Jul 27.

Results Reference

derived

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The Effect of Intranasal Insulin on Hepatic and Intestinal Triglyceride-rich Lipoprotein Production

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