Low Dose Fat-Induced Insulin Resistance

NCT ID: NCT03479671

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-01
• Study Completion Date: 2026-01-31

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.

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance; Insulin Sensitivity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Saline

Insulin sensitivity (rate of glucose disposal)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Low Dose Fatty Acids

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

Group Type: EXPERIMENTAL

Intralipid, 20% Intravenous Emulsion

Intervention Type: DRUG

Fatty Acid Infusion, either in low-dose (30 ml/hr) or medium-dose (60 ml/hr)

Medium Dose Fatty Acids

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

Group Type: EXPERIMENTAL

Intralipid, 20% Intravenous Emulsion

Intervention Type: DRUG

Fatty Acid Infusion, either in low-dose (30 ml/hr) or medium-dose (60 ml/hr)

Interventions

Intralipid, 20% Intravenous Emulsion

Fatty Acid Infusion, either in low-dose (30 ml/hr) or medium-dose (60 ml/hr)

Intervention Type: DRUG

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:

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 44 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Zoltan Arany

Associate Professor Of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zoltan P Arany, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor of Medicine

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Paola Alvarado, MS

Role: CONTACT

Paola.Alvarado@Pennmedicine.upenn.edu

215-746-2081

Michael D Neinast, BS

Role: CONTACT

mneinast@pennmedicine.upenn.edu

469-323-7470

Facility Contacts

Paola Alvarado, B.S.

Role: primary

Paola.Alvarado@Pennmedicine.upenn.edu

2157462081

Other Identifiers

831425

Identifier Type: -

Identifier Source: org_study_id