Epigenetic Regulation of Adipose Tissue Distribution in Obesity

(Eiffel 2 Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Translational Research Institute for Metabolism and Diabetes, Florida

Must not be taking: Blood thinners, Antiplatelets, Steroids, others

Disqualifiers: Diabetes, Hypertension, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how different body types store fat, focusing on whether someone is more "apple-shaped" or "pear-shaped." Researchers will use imaging scans and tissue samples to gather data. The trial seeks healthy women and men with a BMI between 23 and 35, particularly women who identify as more apple- or pear-shaped based on their waist-to-hip ratio. This study targets individuals who have maintained a stable weight and have not experienced major health changes recently. As an unphased trial, it offers participants the opportunity to contribute to groundbreaking research on body fat distribution.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications known to influence glucose, fat, and/or energy metabolism within the last 3 months. If you are on blood thinners or antiplatelet medications, you may need to stop them for biopsy and testing procedures.

What prior data suggests that these methods are safe for studying fat distribution?

Research shows that the treatments in this study are generally safe. Adipose tissue biopsies, which involve taking a small sample of fat tissue, have been used in other studies without major issues. This common procedure helps researchers understand changes in body fat.

DEXA, MRI, and MRS scans are imaging tests that measure body fat and its location. Research indicates these methods are non-invasive, commonly used, and safe, providing valuable information about fat storage in the body.

The FSIGTT, or frequently sampled intravenous glucose tolerance test, involves taking blood samples to assess how the body processes sugar. Studies use this test to check insulin sensitivity, and it is generally well-tolerated.

Overall, previous research has used these treatments with few reported problems, suggesting they are safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to uncover how our genes influence where fat is stored in the body, particularly in those with obesity. Unlike current treatments that focus on reducing overall body fat through diet, exercise, or medication, this approach dives into the genetic and molecular reasons behind fat distribution, like why some people store more fat around their hips versus their belly. This could lead to more personalized and effective strategies for managing obesity by targeting specific genetic pathways, potentially transforming how we approach weight management in the future.

What evidence suggests that this trial's methods could be effective for understanding fat distribution in obesity?

Studies have shown that where and how people store fat can impact their health. For example, having more fat around the belly (an "apple" shape) might increase the risk of heart problems more than having fat around the hips and thighs (a "pear" shape). Research suggests that genes and other factors, known as epigenetics, which can switch genes on or off, might influence these differences in fat storage. By understanding these patterns, scientists hope to learn more about preventing and treating health issues related to obesity. This trial will compare different groups, including women with "pear" and "apple" shapes and men with "apple" shapes, to discover how fat distribution affects health. The study does not test any direct treatments.

Who Is on the Research Team?

Steven R Smith, MD

Principal Investigator

Study Principal Investigator

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-45 with a BMI of 23-35, stable weight in the last three months, non-smokers, not pregnant or postpartum beyond nine months. Excluded are those with serious health conditions like uncontrolled hypertension, kidney/liver disease, recent heart attacks or cancer, untreated thyroid issues or certain mental illnesses.

Inclusion Criteria

HbA1C <6.0%

Weight stable (± 3 kg) during the 3 months prior to enrollment

Women must be > 9 months post-partum

Exclusion Criteria

Postmenopausal women

You have received an organ transplant in the past.

Creatinine > 2x upper limit of laboratory reference range, or known diagnosis of kidney disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo biopsies and subsequent in vitro culture and analysis of adipose tissue

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adipose tissue biopsies
• Dual-energy X-ray absorptiometry (DEXA)/ Magnetic resonance imaging (MRI) and Magnetic resonance spectroscopy (MRS)
• FSIGTT/ RMR

Trial Overview Researchers are studying how adults store fat differently by using tests like FSIGTT/RMR to measure insulin sensitivity and metabolism; DEXA/MRI/MRS scans to visualize body composition; and adipose tissue biopsies to examine fat distribution at a cellular level.

How Is the Trial Designed?

Group I: Group A- Women- Healthy 'pears' Active Control 3 Interventions

This group will consist of healthy women with a BMI between 23 and 35 kg/m2 as a waist-to-hip ratio of 0.78 or less.

Group II: Group B- Women- Healthy 'apples' Active Control 3 Interventions

The group will consist of healthy women with a BMI between 23 and 35 kg/m2 as a waist-to-hip ratio of 0.85 or more.

Group III: Group C- Men- Healthy 'apples' Active Control 3 Interventions

The group will consist of men with a BMI between 23 and 35 kg/m2.

Who Is Running the Clinical Trial?

Translational Research Institute for Metabolism and Diabetes, Florida

Lead Sponsor

Trials

41

Recruited

3,600+

AdventHealth Translational Research Institute

Lead Sponsor

Trials

51

Recruited

5,900+

Sanford-Burnham Medical Research Institute

Collaborator

Trials

9

Recruited

770+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9098964/

Assessing Obesity-Related Adipose Tissue Disease (OrAD) to ... Biopsies were collected during surgery, and used to assess fibrosis in liver, subcutaneous and omental adipose tissues by picrosirius red ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S000291652323436X

Subcutaneous adipocyte size and body fat distribution Our data show that larger quantities of fat in the lower body may be the critical factor that dictates the ability of subcutaneous adipose tissue to expand to ...

3. nature.com nature.com/articles/s41586-024-08165-7

Adipose tissue retains an epigenetic memory of obesity ... We show that both human and mouse adipose tissues retain cellular transcriptional changes after appreciable weight loss.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/oby.20417

Molecular and morphologic characterization of superficial‐ ... In this study, we employed microarray and morphological techniques to better investigate SSAT and DSAT in a cohort of severely obese patients, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11009187/

Percutaneous biopsies of skeletal muscle and adipose ... Biopsies of muscle and adipose tissue (AT) are useful tools to gain insights into the aging processes in these tissues.