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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how obesity affects the brain's ability to transport glucose, a key energy source. Researchers are investigating whether higher levels of certain fatty acids in the blood might alter brain function related to glucose. Participants will receive either an Intralipid, 20% Intravenous Emulsion (a fat emulsion), or a saline infusion to assess its impact on brain metabolism. Ideal participants are non-diabetic individuals who are either of normal weight or have obesity and have not recently followed a ketogenic diet or experienced significant weight changes. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel approach.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Intralipid, a 20% fat solution administered through an IV, is usually safe. It is often used for individuals needing extra nutrition in this manner. However, some may react to it, especially if allergic to ingredients like eggs, soybeans, or peanuts.

Intralipid has been studied and used for a long time, demonstrating its safety. Individuals with conditions like obesity or diabetes might face a higher risk of side effects, but doctors typically manage these. Common side effects include fever, chills, or a rash, though they are infrequent. Participants should inform a doctor about any allergies or health conditions before joining a trial involving Intralipid. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using Intralipid, a 20% intravenous emulsion, for obesity treatment because it works differently than most current options. Unlike traditional weight-loss medications that suppress appetite or increase metabolism, Intralipid elevates fatty acid levels directly through an IV infusion. This novel approach could provide more immediate metabolic effects, potentially leading to faster outcomes. Additionally, the delivery method via IV allows for precise control of dosage and timing, which might enhance its effectiveness and reduce side effects compared to oral medications.

What evidence suggests that Intralipid 20% might be an effective treatment for obesity?

In this trial, non-diabetic, normal-weight individuals will receive either Intralipid 20% Intravenous Emulsion or a saline placebo. Research has shown that Intralipid 20% Intravenous Emulsion can be beneficial in certain medical situations. Past studies found it helps maintain a healthy nitrogen balance in the body, which is crucial for overall health. This treatment also addresses essential fatty acid deficiencies by supplying necessary nutrients. The trial aims to determine if Intralipid can aid in managing obesity by influencing how the brain processes glucose. Early results in other areas suggest promise, but more research is needed specifically for obesity. ^{6 7 8 9 10}

Who Is on the Research Team?

Janice Jin Hwang, MD, MHS

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

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

My high blood pressure is not under control.

Triglycerides >200 mg/dL

Abnormal PT/PTT/INR

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10411978/

Effect of a 20% intravenous fat emulsion therapy ... Our review provides a moderate level of evidence that intravenous fat emulsion therapy is effective in improving reproductive outcomes among women with RPL/RIF.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/2109121/

Comparative clearance of two new fat emulsions ... These results suggest that the three fat emulsions are similarly eliminated from the blood stream and do not result in acute intolerance.

3. withpower.com withpower.com/trial/phase-2-11-2020-daa3c

Fatty Acid Elevation for Obesity In a study involving 59 patients, both Intralipid 10% and Intralipid 20% were found to be equally effective in maintaining nitrogen balance and correcting ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S026156149880040X

Comparison between two fat emulsions: Intralipid® 30%vs ... During the infusion of the fat emulsion, a lower median plasma concentration of triglycerides, phospolipids and free cholesterol was observed in patients who ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/017643s083,018449s050s051,019942s021,020248s027s028lbl.pdf

Intralipid - accessdata.fda.gov When Intralipid is administered to correct essential fatty acid deficiency (EFAD), supply 8% to. 10% of caloric input from Intralipid in order to provide ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/018449s049lbl.pdf

Intralipid® 20% (A 20% IV Fat Emulsion) The daily dosage should not exceed 2.5 g of fat/kg of body weight (12.5 mL of Intralipid20% per kg). Intralipid 20%. (A 20% I.V. Fat Emulsion) should make up ...

7. editor.fresenius-kabi.us editor.fresenius-kabi.us/SDSSheets/Intralipid__SDS_NA2015_030323_FINAL.pdf

Intralipid - Fresenius Kabi USA Reactivity: Hazardous reactions will not occur under normal conditions. Contact with acids will release heat. Page 4. Intralipid. Safety Data ...

8. freseniuskabinutrition.com freseniuskabinutrition.com/wp-content/uploads/2024/03/Intralipid-2023-Fact-Sheet_4C.pdf

Intralipid® 20% - Fresenius Kabi CONTRAINDICATIONS: Known hypersensitivity to egg, soybean, peanut, or any of the active or inactive ingredients in Intralipid. Severe disorders of lipid ...

9. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61e025f1-a38e-4af2-9e18-13ea12977cf5

Label: INTRALIPID- iv fat emulsion emulsion - DailyMed Patients with conditions such as inherited lipid disorders, obesity, diabetes mellitus, or metabolic syndromes have a higher risk of developing ...

10. rsc.niaid.nih.gov rsc.niaid.nih.gov/sites/default/files/SUMMARY%20OF%20PRODUCT%20CHARACTERISTICS%20of%20Intralipid.pdf

SUMMARY OF PRODUCT CHARACTERISTICS of Intralipid On the first day of infusion it is advisable to administer 5 ml Intralipid 20% per kg body weight or 10 ml Intralipid. 10% per kg body weight.