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

27 Participants Needed

Trial Summary

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 data supports the effectiveness of this treatment for regulating adipose tissue distribution in obesity?

The research shows that MRI and MRS can reliably measure and analyze different types of fat tissue in the body, which is important for understanding how fat is distributed in obesity. This suggests that these imaging techniques are effective tools for studying and potentially managing obesity by providing detailed information about fat distribution. ^{1 2 3 4 5}

Is the treatment involving adipose tissue biopsies, DEXA/MRI, and MRS safe for humans?

The research articles provided do not contain specific safety data for the procedures mentioned, such as adipose tissue biopsies, DEXA/MRI, and MRS, in humans. ^{6 7 8 9 10}

How does this treatment for obesity differ from other treatments?

This treatment is unique because it focuses on the epigenetic regulation of fat distribution, specifically through changes in DNA methylation and histone modifications, which are chemical changes that can turn genes on or off. Unlike traditional treatments that may focus on diet, exercise, or medication, this approach targets the underlying genetic and molecular mechanisms that influence how and where fat is stored in the body. ^{6 9 11 12 13}

What is the purpose of this trial?

The purpose of this study is to collect data to help researchers better understand the different ways that women or men store fat (apple shape versus pear shape).

Research Team

Steven R Smith, MD

Principal Investigator

Study Principal Investigator

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

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

Comparison of methods for assessing abdominal adipose tissue from magnetic resonance images. [2016]

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

Compensation of RF field and receiver coil induced inhomogeneity effects in abdominal MR images by a priori knowledge on the human adipose tissue distribution. [2012]

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

In vivo triglyceride composition of abdominal adipose tissue measured by 1 H MRS at 3T. [2018]

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

Feasibility and reproducibility of free fatty acid profiling in abdominal adipose tissue with 1H-magnetic resonance spectroscopy at 3 T: differences between lean and obese individuals. [2014]

5. England pubmed.ncbi.nlm.nih.gov

Breast adipose tissue attenuation as a novel imaging biomarker for cardiometabolic risk. [2022]

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

Histone variants and their post-translational modifications in primary human fat cells. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Differential open chromatin profile and transcriptomic signature define depot-specific human subcutaneous preadipocytes: primary outcomes. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Nuclear and chromatin rearrangement associate to epigenome and gene expression changes in a model of in vitro adipogenesis and hypertrophy. [2023]

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

Human adipose tissue H3K4me3 histone mark in adipogenic, lipid metabolism and inflammatory genes is positively associated with BMI and HOMA-IR. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Genome Profiling of H3k4me3 Histone Modification in Human Adipose Tissue during Obesity and Insulin Resistance. [2021]

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

Limits of Fat Quantification in the Presence of Iron Overload. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Dynamic DNA methylation landscape defines brown and white cell specificity during adipogenesis. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Human adipogenesis is associated with genome-wide DNA methylation and gene-expression changes. [2018]