Low-Dose Fatty Acids for Insulin Resistance

(BCAA Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Zoltan P Arany, MD, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Pennsylvania

Must not be taking: Systemic steroids

Disqualifiers: Diabetes, Hypertension, Hyperlipidemia, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic steroids, you may need to adjust your dose to 5 mg of prednisone daily or an equivalent dose of hydrocortisone.

What data supports the effectiveness of the treatment Intralipid for insulin resistance?

Intralipid, a fatty acid emulsion, has been shown to correct essential fatty acid deficiencies and is well tolerated in patients, which may indirectly support its potential benefits in managing insulin resistance by improving overall metabolic health. ^{1 2 3 4 5}

Is the use of low-dose fatty acids, like Intralipid, generally safe for humans?

Intralipid, a type of fat emulsion, has been used safely in humans for over 40 years, primarily as a nutritional supplement. Studies show it is generally well-tolerated, but caution is advised in severely ill patients due to potential metabolic effects like increased fat levels in the blood. Newer formulations with alternative oils, such as fish oil, may offer additional safety benefits. ^{3 6 7 8 9}

How does the drug Intralipid differ from other treatments for insulin resistance?

Intralipid is unique because it is a fat emulsion that can be used to deliver fatty acids intravenously, potentially affecting insulin resistance by altering free fatty acid levels and promoting glucose conservation. Unlike typical oral medications for insulin resistance, Intralipid is administered directly into the bloodstream, which may lead to different metabolic effects. ^{1 3 4 10 11}

Research Team

Zoltan P Arany, MD, PhD

Principal Investigator

Associate Professor of Medicine

Eligibility Criteria

Healthy volunteers who can consent and follow study procedures, without soy or egg allergies, severe heart disease, kidney issues, high cholesterol/triglycerides, diabetes history in family, BMI between 19-27 kg/m2. Must not have used investigational drugs recently or have certain chronic diseases.

Inclusion Criteria

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

Exclusion Criteria

Use of any investigational agents within 4 weeks of enrollment

I have a history of diabetes.

You are allergic to metal, specifically aluminum.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 6-hour hyperinsulinemic-euglycemic clamp with low-dose fatty acid infusion (30ml/hr) to test insulin sensitivity

1 day

1 visit (in-person)

Dose Confirmation

If initial low-dose does not achieve desired insulin resistance, participants return for another 6-hour clamp with medium-dose fatty acid infusion (60ml/hr)

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-3 weeks

Treatment Details

Interventions

• Intralipid (Fatty Acid Infusion)

Trial Overview The trial is testing how a low dose of fatty acids (Intralipid/heparin infusion) affects insulin sensitivity in healthy people to find the right dose that causes mild insulin resistance for future research.

Participant Groups

Group I: Medium Dose Fatty Acids Experimental Treatment 1 Intervention

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

Group II: Low Dose Fatty Acids Experimental Treatment 1 Intervention

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

Group III: Saline Active Control 1 Intervention

Insulin sensitivity (rate of glucose disposal)

Intralipid is already approved in Canada for the following indications:

Approved in Canada as Intralipid for:

• Parenteral nutrition
• Caloric supplementation

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Pennsylvania Philadelphia, PA

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2118

Patients Recruited

45,270,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dose-related hypoglycemic effects of insulin emulsions incorporating highly purified EPA and DHA. Morishita, M., Kajita, M., Suzuki, A., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid emulsion use precluding renal replacement therapy. Rodríguez, B., Wilhelm, A., Kokko, KE.[2014]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Intralipid 10% and Intralipid 20% as a source of energy and essential fatty acids--a multicenter study. Meng, HC., Zayan, M., Kahn, S., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choice of Lipid Emulsion Determines Inflammation of the Gut-Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition. Lou, PH., Lucchinetti, E., Wawrzyniak, P., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fat emulsion for intravenous administration: clinical experience with intralipid 10%. Hansen, LM., Hardie, BS., Hidalgo, J.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid injectable emulsions: Pharmacopeial and safety issues. Driscoll, DF.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parenteral lipids: safety aspects and toxicity. Wanten, GJ.[2014]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The problem of dosage and importance of fats in parenteral feeding]. Förster, H., Quadbeck, R., Anschütz, A.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parenteral Lipid Tolerance and Adverse Effects: Fat Chance for Trouble? Wanten, GJ.[2022]

Infusing a fat emulsion in eight metabolically normal subjects led to significant increases in serum triglycerides and free fatty acids, along with a 30% rise in glucose levels and a 22% decrease in alanine, indicating a shift in metabolism towards fat utilization.

The fat emulsion infusion also resulted in a four-fold increase in 3-hydroxybutyrate, suggesting that it stimulates ketogenesis and helps conserve glucose, while having minimal impact on hormonal levels like insulin and glucagon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of intravenous infusion of a ten percent soybean emulsion on hormones, amino acids and other substrates in blood. Chikenji, T., Yokoyama, M., Mashima, Y., et al.[2019]

In a study involving 90 critically ill patients (55 septic and 35 trauma), both 30% and 20% fat emulsions used in total parenteral nutrition were found to be clinically safe, showing no significant adverse effects on renal, hematologic, or hepatic functions.

The 30% long-chain triglyceride emulsion resulted in fewer lipid metabolic disturbances compared to the 20% emulsion, suggesting it may be a better option for managing fat intake in septic patients during parenteral nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and metabolic tolerance of a concentrated long-chain triglyceride lipid emulsion in critically ill septic and trauma patients. García-de-Lorenzo, A., López-Martínez, J., Planas, M., et al.[2017]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The dose-related hypoglycemic effects of insulin emulsions incorporating highly purified EPA and DHA. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Lipid emulsion use precluding renal replacement therapy. [2014]

3. Sweden pubmed.ncbi.nlm.nih.gov

Comparison of Intralipid 10% and Intralipid 20% as a source of energy and essential fatty acids--a multicenter study. [2013]

4. Germany pubmed.ncbi.nlm.nih.gov

Choice of Lipid Emulsion Determines Inflammation of the Gut-Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Fat emulsion for intravenous administration: clinical experience with intralipid 10%. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Lipid injectable emulsions: Pharmacopeial and safety issues. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Parenteral lipids: safety aspects and toxicity. [2014]

8. Switzerland pubmed.ncbi.nlm.nih.gov

[The problem of dosage and importance of fats in parenteral feeding]. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Parenteral Lipid Tolerance and Adverse Effects: Fat Chance for Trouble? [2022]

10. England pubmed.ncbi.nlm.nih.gov

Effects of intravenous infusion of a ten percent soybean emulsion on hormones, amino acids and other substrates in blood. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Safety and metabolic tolerance of a concentrated long-chain triglyceride lipid emulsion in critically ill septic and trauma patients. [2017]