Ex Vivo Transformation of White Adipose Tissue (WAT) Into Brown Adipose Tissue (BAT) in Morbidly Obese Patients Using the Ex Vivo Adipocyte Expansion (ExAdEx) Approach: Proof of Concept. From White to Brown Adipose Tissue (OBADEX)

Obesity and metabolic associated diseases such as type 2 diabetes, NASH, cardiovascular diseases, are the dysregulation of energy homeostasis associated with an imbalance between different types of adipose tissues (ATs). White AT (WAT) which stores energy and functions as a fat storage depot, is fibrotic whith chronic inflammation and is found in excess. On the other hand, brown and beige ATs (BATs), considered as the good ATs because they regulate energy expenditure, are almost undetectable in individuals with obesity. In addition, BAT and WAT produce different hormones that are involved in the control of energy homeostasis via central and peripheral actions. A promising emerging therapeutic approach is to restore BAT in patients with severe obesity in two ways, i) by stimulating BAT in individuals with obesity by pharmacological treatment, ii) by injecting BAT into individuals with obesity using a cell-based therapy approach. However, the development of these two proposals is limited both by the lack of in vitro preclinical BAT models relevant for the screening and validation stages of drug candidates, and by the lack of physiologically functional BAT compatible with tissue graft. The bottleneck is the absence of an unlimited source of human BAT.

The ExAdEX technology makes possible in vitro to turn WAT derived from lean donors into BAT. This new technology offers the possibility of having in vitro predictive human 3D models suitable for the identification and characterization of compounds affecting AT biology, and paves the way for the production of BAT for cell-based therapy of obesity and associated metabolic diseases.

The Primary objective of the study is addressed the effectiveness of the ExAdEx process to induce, ex vivo, the conversion of WAT from obese patients into TAB. The secondary objectives are 1) to compare the efficacy for conversion into BAT when WAT derived from either from visceral or from subcutaneous AT; 2) to investigate the capacity of the ExAdEX-BAT to produce the FGF21 and adiponectin batokines and to respond to insulin.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Sampling

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Alpes-Mritimes
    • Nice, Alpes-Mritimes, France, 06300
      • Hôpital Archet 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Inclusion:

• Karnofsky index > 70
• IMC > 35 kg/m2 associated with a comorbidity : hypertension ; type 2 diabetes; disabling osteoarthritis; sleep apnea syndrome with device.
• Failure of a previous well-conducted medical treatment (multidisciplinary management of more than six months preoperatively)

Exclusion Criteria:

• Psychiatric counter-indications
• Anaesthetic counter-indications
• Progressive neoplastic pathologies
• Chronic alcoholism
• Severe uncontrolled infection
• Renal failure (Cockroft's clearance <30ml/min)
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sampling	Other: Sampling; During thier bariatric surgery, samples of adipose tissue will be done

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WAT/TAB conversion	WAT/BAT conversion efficiency based on the expression level of the UCP1 marker in the cultures	At 1 month

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2023
• Primary Completion (Actual): January 18, 2024
• Study Completion (Actual): January 18, 2024

Study Registration Dates

• First Submitted: April 25, 2023
• First Submitted That Met QC Criteria: April 25, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 22-AOIP-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No