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

NCT05843747 | Completed

• 1 other identifier: 22-AOIP-04
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity

Outcome Measures

Primary Outcomes (1)

• WAT/TAB conversion

  WAT/BAT conversion efficiency based on the expression level of the UCP1 marker in the cultures

  At 1 month

Study Arms (1)

Sampling

EXPERIMENTAL

Other: Sampling

Interventions

Sampling OTHER

During thier bariatric surgery, samples of adipose tissue will be done

Sampling

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (1)

Hôpital Archet 2

Nice, Alpes-Mritimes, 06300, France

Location

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2023
• First Posted: May 6, 2023
• Study Start: November 13, 2023
• Primary Completion: January 18, 2024
• Study Completion: January 18, 2024
• Last Updated: January 31, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)