Fatty Acid Elevation for Obesity

Recruiting at 3 trial locations

Overseen By Cassandra Donahue, RDN, LDN, CDCES

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Yale University

Must not be taking: Steroids, Metabolism-altering drugs

Disqualifiers: Hepatic, Renal, Neurologic, Psychiatric, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 hours

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves giving healthy individuals either a fat solution or a saltwater solution to see how it affects their brain's ability to transport glucose. The study focuses on non-diabetic, normal weight people to understand how sudden increases in blood fatty acids impact brain energy use. Researchers hope to learn more about brain glucose transport in relation to obesity.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications, vitamins, or supplements that can alter brain metabolism or lipids to participate in this trial.

What data supports the effectiveness of the treatment Intralipid 20% for obesity?

The research shows that Intralipid 20% is effective in providing essential fatty acids and maintaining nitrogen balance, which are important for overall health. However, there is no direct evidence from the studies provided that supports its effectiveness specifically for treating obesity. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Intralipid, a type of intravenous fat emulsion, has been used safely in various medical settings. Studies show it does not cause significant heart-related side effects, even in patients with heart conditions, and is well tolerated without adverse effects in clinical trials. ^{1 2 6 7 8}

How is the treatment Intralipid 20% IV Fat Emulsion unique for obesity?

Intralipid 20% IV Fat Emulsion is unique for obesity as it involves intravenous administration of a fat emulsion, which increases free fatty acid levels in the blood, potentially affecting blood pressure and endothelial function. This approach is different from typical oral medications or lifestyle interventions for obesity. ^{1 9 10 11 12}

Research Team

Janice Jin Hwang, MD, MHS

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

This trial is for adults aged 18-45 with obesity (BMI >30 kg/m2) or normal weight (BMI 17-25 kg/m2), and HbA1C levels below 6.5%. Participants should not have significant health issues like liver, kidney, or heart diseases, uncontrolled high blood pressure, abnormal thyroid or clotting tests, recent drastic weight changes, substance abuse problems, or be pregnant/breastfeeding.

Inclusion Criteria

HbA1C <6.5%

Normal weight individuals: BMI 17-25 kg/m^2

My BMI is over 30.

Exclusion Criteria

Triglycerides >200 mg/dL

My high blood pressure is not under control.

Abnormal PT/PTT/INR

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of either Intralipid or normal saline for 12 hours

12 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Intralipid, 20% Intravenous Emulsion
• Placebos

Trial Overview The study aims to understand how brain glucose transport is affected in obese individuals by temporarily raising fatty acid levels using Intralipid. A placebo group will serve as a comparison. The effects on brain metabolism are monitored through magnetic resonance spectroscopy (MRS).

Participant Groups

Group I: Non-diabetic, normal weight individuals receiving Intralipid Experimental Treatment 1 Intervention

Non-diabetic, normal weight individuals receiving Intralipid. Participants will receive an infusion of Intralipid 20% for 12 hours through an IV (prior to and during scan #2)

Group II: Non-diabetic, normal weight individuals receiving saline Placebo Group 1 Intervention

Non-diabetic, normal weight individuals receiving saline. Participants will receive an infusion of normal saline (1:1 randomization) at 30 ml/hr for 12 hours through an IV (prior to and during scan #2

Intralipid, 20% Intravenous Emulsion is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Intralipid 20% for:

• Parenteral nutrition
• Caloric supplementation

Approved in European Union as Intralipid 20% for:

• Parenteral nutrition
• Caloric supplementation

Approved in Canada as Intralipid 20% for:

• Parenteral nutrition
• Caloric supplementation

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

In a study involving 59 patients, both Intralipid 10% and Intralipid 20% were found to be equally effective in maintaining nitrogen balance and correcting essential fatty acid deficiency over a seven-day period.

Both concentrations of Intralipid were well tolerated by patients, with no adverse effects reported, indicating their safety for use in clinical settings.

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]

In a study involving human volunteers, intravenous infusions of fat emulsions showed that intralipid resulted in significantly higher blood triglyceride levels compared to lipofundin S, indicating differences in how these emulsions are metabolized.

The study suggests that guidelines for intravenous fat dosage should consider the type of fat preparation used, and it emphasizes the importance of closely monitoring triglyceride levels during infusion to prevent complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Differences in the elimination of intravenously administered intralipid and lipofundin S]. Förster, H.[2013]

Intravenous fat emulsion (IVFE) is crucial for providing calories and essential fatty acids to patients on parenteral nutrition, supporting their cellular function and metabolism.

IVFE can also be used effectively in treating overdoses of lipophilic drugs due to its ability to bind these medications, highlighting its dual role in patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Intravenous Lipid Emulsion Therapy. Spray, JW.[2018]

Structured-lipid emulsions, made from a mix of medium-chain and long-chain triglycerides, have shown improved nitrogen balance and lipid metabolism in human studies compared to traditional long-chain triglycerides, although results are not as strong as in animal studies.

These emulsions appear to cause less elevation in liver function tests and do not negatively impact the reticuloendothelial system, suggesting a potentially safer profile than standard intravenous fat emulsions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structured triglyceride emulsions in parenteral nutrition. Chambrier, C., Lauverjat, M., Bouletreau, P.[2017]

The study successfully developed a stable intravenous lipid emulsion (IVLE) using superolein palm oil, with optimal preparation parameters including 800 psi pressure and 7 homogenization cycles, resulting in a particle size of 252.60 nm.

SoLE 20% IVLE was found to be safe for intravenous use in rabbits, showing no significant changes in blood lipid levels or liver enzyme profiles after administration, indicating its potential for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new alternative for intravenous lipid emulsion 20% w/w from superolein oil and its effect on lipid and liver profiles in an animal model. Amran, MHH., Zulfakar, MH., Danik, MF., et al.[2020]

A case report of an extremely preterm infant who received an accidental overdose of intravenous fat emulsion (IVFE) highlights the potential risks of rapid lipid infusion, leading to severe complications like metabolic acidosis and hemodynamic instability.

The successful use of double-volume exchange transfusion in this infant effectively normalized serum triglyceride levels and improved clinical outcomes, suggesting it is a viable treatment option for managing severe hypertriglyceridemia in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful exchange transfusion in extremely preterm infant after symptomatic lipid overdose. Rodríguez-Castaño, MJ., Iglesias, B., Arruza, L.[2018]

In a study involving 13 adult patients recovering from cardiopulmonary bypass, two types of 10% intravenous fat emulsions (Liposyn and Intralipid) were administered without causing significant changes in key hemodynamic parameters such as cardiac output and blood pressure.

The results suggest that these fat emulsions are safe for use in patients with severe cardiac impairment after open heart surgery, as they do not negatively impact heart function during recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of intravenous fat emulsions in patients with heart disease. Fisch, D., Abel, RM.[2023]

Intralipid, an intravenous lipid emulsion, has been found to effectively treat bupivacaine-induced cardiac arrest and may reverse other toxicities, highlighting its potential as a therapeutic agent.

The exact mechanism of action for Intralipid remains debated, with some studies suggesting it works through the properties of lipids while others indicate it may activate cellular pathways, which could lead to new protective treatments for organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid Emulsion, More Than Reversing Bupivacaine Cardiotoxicity: Potential Organ Protection. Motayagheni, N., Phan, S., Nozari, A., et al.[2018]

Infusion of Intralipid significantly increased free fatty acids (FFA) and blood pressure in obese healthy subjects, leading to endothelial dysfunction, as indicated by a decrease in flow-mediated dilatation (FMD).

When combined with dextrose, the infusion of Intralipid did not further increase blood pressure but still resulted in similar endothelial dysfunction, suggesting that both high FFA and hyperglycemia can negatively impact vascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular effects of intravenous intralipid and dextrose infusions in obese subjects. Gosmanov, AR., Smiley, DD., Peng, L., et al.[2022]

Intravenous infusion of a fat emulsion (Intralipid) in six near-term patients before delivery significantly altered the fatty acid composition in both maternal triglycerides and fetal lipids, indicating a direct impact on lipid metabolism during pregnancy.

The infusion led to substantial differences in free fatty acid and triglyceride concentrations between umbilical venous and arterial blood, particularly for fatty acids that were abundant in the emulsion, suggesting that the emulsion can effectively influence fetal nutrient availability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The passage of fat emulsion across the human placenta. Elphick, MC., Filshie, GM., Hull, D.[2019]

A systematic review of three randomized controlled trials involving 110 adults on home parenteral nutrition (HPN) found that alternative intravenous lipid emulsions (IVLEs) like SMOF showed improved antioxidant status and better liver function compared to conventional soybean oil (SO) IVLEs.

All IVLEs tested, including SMOF and olive oil-SO, were clinically safe and did not lead to essential fatty acid deficiency, but SMOF provided a more favorable omega-6/omega-3 fatty acid ratio, suggesting potential metabolic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of different intravenous lipid emulsions on fatty acid status and laboratory and clinical outcomes in adult patients receiving home parenteral nutrition: A systematic review. Jones, CJ., Calder, PC.[2019]

Intravenous fat emulsions (IFEs) have evolved from soybean oil-based formulations, which can cause complications like inflammation and liver disease, to a mixed-oil (MO) IFE that combines soybean oil, medium-chain triglycerides, olive oil, and fish oil, aiming for a better safety profile.

Early results from small, short-term trials of the MO IFE (Smoflipid) show promising improvements in liver function, triglyceride levels, and a healthier omega-3 to omega-6 fatty acid ratio, but larger long-term studies are necessary to confirm these benefits in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergence of Mixed-Oil Fat Emulsions for Use in Parenteral Nutrition. Mundi, MS., Martindale, RG., Hurt, RT.[2019]

References

1. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Differences in the elimination of intravenously administered intralipid and lipofundin S]. [2013]

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

Review of Intravenous Lipid Emulsion Therapy. [2018]

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

Structured triglyceride emulsions in parenteral nutrition. [2017]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A new alternative for intravenous lipid emulsion 20% w/w from superolein oil and its effect on lipid and liver profiles in an animal model. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Successful exchange transfusion in extremely preterm infant after symptomatic lipid overdose. [2018]

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

Hemodynamic effects of intravenous fat emulsions in patients with heart disease. [2023]

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

Lipid Emulsion, More Than Reversing Bupivacaine Cardiotoxicity: Potential Organ Protection. [2018]

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

Vascular effects of intravenous intralipid and dextrose infusions in obese subjects. [2022]

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

The passage of fat emulsion across the human placenta. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Influence of different intravenous lipid emulsions on fatty acid status and laboratory and clinical outcomes in adult patients receiving home parenteral nutrition: A systematic review. [2019]

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

Emergence of Mixed-Oil Fat Emulsions for Use in Parenteral Nutrition. [2019]