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Low Dose Fat-Induced Insulin Resistance (BCAA)

Primary Purpose

Diabetes Mellitus, Type 2, Insulin Resistance, Insulin Sensitivity

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Intralipid, 20% Intravenous Emulsion
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Diabetes Mellitus, Type 2

Eligibility Criteria

18 Years - 39 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol

Exclusion Criteria:

  • History of diabetes
  • History of diabetes in more than one first-degree relative
  • Body mass index (BMI) <19 or >27 kg/m2
  • HbA1c >5.7%
  • Blood Pressure: systolic >160 mmHg or diastolic > 100 mmHg
  • Baseline hemoglobin concentration < 11 g/dl in women and < 12 g/dl in men
  • Estimated glomerular filtration rate < 55 ml/min/1.73 m2 (calculated using the subject's measured serum creatinine and the Modification of Diet in Renal Disease [MDRD] study estimation formula).
  • Presence of soy or egg allergies (due to possible reactions with fat infusate)
  • For female participants: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
  • Known active alcohol or substance abuse
  • Use of tobacco within the previous year

  • Severe co-existing cardiac disease, characterized by any one of these conditions:

    1. history of myocardial infarction within past 6 months;
    2. history of ischemia on functional cardiac exam within the last year;
    3. history of left ventricular ejection fraction < 30%.
  • Persistent elevation of liver function tests > 1.5 times normal upper limits
  • Hyperlipidemia (fasting LDL cholesterol > 130 mg/dl, treated or untreated; and/or fasting triglycerides > 200 mg/dl)
  • Receiving treatment for a medical condition requiring chronic use of systemic steroids, except for the use of ≤ 5 mg prednisone daily, or an equivalent physiological dose of hydrocortisone
  • Presence of a seizure disorder
  • Use of any investigational agents within 4 weeks of enrollment
  • Any medical condition, which in the opinion of the investigator, will interfere with the safe completion of the study
  • History of pancreatitis
  • Presence of a metal allergy (aluminum)

Sites / Locations

  • University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

Saline

Low Dose Fatty Acids

Medium Dose Fatty Acids

Arm Description

Insulin sensitivity (rate of glucose disposal)

Insulin sensitivity (rate of glucose disposal) in response to 30 ml/hr fatty acid infusion

Insulin sensitivity (rate of glucose disposal) in response to 60 ml/hr fatty acid infusion

Outcomes

Primary Outcome Measures

Insulin Sensitivity
Rate of Glucose Disposal (mg/kg/min)

Secondary Outcome Measures

Full Information

First Posted
March 20, 2018
Last Updated
January 13, 2023
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT03479671
Brief Title
Low Dose Fat-Induced Insulin Resistance
Acronym
BCAA
Official Title
A Dose Finding Study for Fat-Induced Insulin Resistance in Healthy Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2020 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary goal of this study is to determine the dose of fatty acids that acutely induces mild insulin resistance in healthy volunteers. We hypothesize that a low-dose of fatty acid infusion (Intralipid/heparin) will cause a mild insulin resistance. The dose of fatty acid infusion that reliably causes mild insulin resistance will be selected for use in future studies.
Detailed Description
This study is designed to test the hypothesis that a low-dose of fatty acid infusion (Intralipid/heparin) will cause mild insulin resistance. This dose-finding study is critical for future studies on free-fatty acid induced insulin resistance. Healthy male and healthy female volunteers will undergo a 6 hour hyperinsulinemic-euglycemic clamp, in order to establish insulin sensitivity parameters in the presence of fatty acid co-infusion. The subjects will then return 1-3 weeks later, and undergo another 6 hour HIE clamp, this time in the presence of low-dose fatty acid co-infusion (30ml/hr). If this dose does not achieve ~25% reduction in the rate of glucose disposal, then the dose-confirmation study will be repeated 1-3 weeks later with a medium-dose fatty acid co-infusion (60ml/hr). A dose-response effect of fatty acids on insulin resistance has been demonstrated before, but not in the precise conditions of our study. This dose-finding study is critical because future studies require a reliable dose of fatty acid infusion, and the exact dose of fatty acid infusion that causes mild insulin resistance may be different in the conditions of our study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, Insulin Resistance, Insulin Sensitivity

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Baseline insulin sensitivity will be measured in healthy volunteers, and then 1-3 weeks later insulin sensitivity will be measured in response to a low-dose fatty acid infusion. If there is no response to this low-dose infusion, then 1-3 weeks later insulin sensitivity will be measured in response to a medium-dose fatty acid infusion.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Saline
Arm Type
No Intervention
Arm Description
Insulin sensitivity (rate of glucose disposal)
Arm Title
Low Dose Fatty Acids
Arm Type
Experimental
Arm Description
Insulin sensitivity (rate of glucose disposal) in response to 30 ml/hr fatty acid infusion
Arm Title
Medium Dose Fatty Acids
Arm Type
Experimental
Arm Description
Insulin sensitivity (rate of glucose disposal) in response to 60 ml/hr fatty acid infusion
Intervention Type
Drug
Intervention Name(s)
Intralipid, 20% Intravenous Emulsion
Intervention Description
Fatty Acid Infusion, either in low-dose (30 ml/hr) or medium-dose (60 ml/hr)
Primary Outcome Measure Information:
Title
Insulin Sensitivity
Description
Rate of Glucose Disposal (mg/kg/min)
Time Frame
6 hours

10. Eligibility

Sex
All
Gender Based
Yes
Gender Eligibility Description
Male or Female at birth.
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol Exclusion Criteria: History of diabetes History of diabetes in more than one first-degree relative Body mass index (BMI) <19 or >27 kg/m2 HbA1c >5.7% Blood Pressure: systolic >160 mmHg or diastolic > 100 mmHg Baseline hemoglobin concentration < 11 g/dl in women and < 12 g/dl in men Estimated glomerular filtration rate < 55 ml/min/1.73 m2 (calculated using the subject's measured serum creatinine and the Modification of Diet in Renal Disease [MDRD] study estimation formula). Presence of soy or egg allergies (due to possible reactions with fat infusate) For female participants: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable. Known active alcohol or substance abuse Use of tobacco within the previous year Severe co-existing cardiac disease, characterized by any one of these conditions: history of myocardial infarction within past 6 months; history of ischemia on functional cardiac exam within the last year; history of left ventricular ejection fraction < 30%. Persistent elevation of liver function tests > 1.5 times normal upper limits Hyperlipidemia (fasting LDL cholesterol > 130 mg/dl, treated or untreated; and/or fasting triglycerides > 200 mg/dl) Receiving treatment for a medical condition requiring chronic use of systemic steroids, except for the use of ≤ 5 mg prednisone daily, or an equivalent physiological dose of hydrocortisone Presence of a seizure disorder Use of any investigational agents within 4 weeks of enrollment Any medical condition, which in the opinion of the investigator, will interfere with the safe completion of the study History of pancreatitis Presence of a metal allergy (aluminum)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Paola Alvarado, MS
Phone
215-746-2081
Email
Paola.Alvarado@Pennmedicine.upenn.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Michael D Neinast, BS
Phone
469-323-7470
Email
mneinast@pennmedicine.upenn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zoltan P Arany, MD, PhD
Organizational Affiliation
Associate Professor of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paola Alvarado, B.S.
Phone
215-746-2081
Email
Paola.Alvarado@Pennmedicine.upenn.edu

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Low Dose Fat-Induced Insulin Resistance

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