Clinical trial NCT05128318: TuLip : Role of the Tumor Environment in Cancer-related Fat Loss
Official title: Study of the Tumor-adipose Tissue Dialogue: Role of Tumor Acidosis in the Induction of Adipocyte Lipolysis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Cancer
Cachexia
Adipose Tissue
Lead sponsor: Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
First posted: 2021-11-22
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Collection of subcutaneous and visceral adipose tissue from patients with BMI \< 30 kg/m2
Primary purpose: BASIC_SCIENCE

Brief summary: Cancer cachexia is defined as a weight loss of more than 5% over the last 6 months, a loss of body fat and muscle atrophy. It is found in 80% of patients with advanced cancer. In this context, white adipose tissue is a particularly interesting target since its depletion precedes the loss of muscle mass, and is sufficient to induce a decrease in the response to anti-cancer treatments and in the survival of patients.

This cachexia is associated with advanced tumors that present acidosis and metastasis. In this clinical study the investigators would like explore the acid environment effect on the human adipose tissue depletion and more specifically on adipocyte lipolysis.

The main objective of the "TuLip" clinical study is therefore to validate in human subcutaneous and visceral adipocytes that factors secreted by tumor cells cultivated in acid tumor environment stimulate the release of lipids from adipose tissue. Adipocytes retrieves from this study will also be used to validate identified potential lipolytic factors derived from these cells.

Detailed description: This study is a monocentric clinical study. Patients with BMI \< 30 kg/m2 will be recruited in the context of programmed abdominal surgery. In this context, subcutaneous and visceral adipose tissue pieces (1-2 cm3) will be collected to explore the lypolytic response of adipocytes ex-vivo to factors secreted by human cancer cell lines.

Eligibility criteria: Inclusion Criteria:

* Programmed surgeries in the abdominal area in the Department of Surgery and Transplantation at Cliniques Universitaires Saint-Luc under the supervision of Prof. Dr. Benoit Navez.
* Hospitalization in the context of surgery
* Caucasian
* Age between 18 and 60 years (included).
* Body mass index less than 30 and greater than or equal to 18.5
* Programmed Nissen fundoplication (to treat hiatal hernia and gastroesophageal reflux) or cholecystectomy (to treat vesicular lithiasis), eventration, or parietal surgery .
* Adults capable of expressing their wishes.
* Understanding French

Exclusion Criteria:

* Body mass index below 18.5 and above 30.
* Patients with cancer, infection, autoimmune or inflammatory disease, metabolic syndrome.
* Patients with beta-blockers, hypoglycemics, anti-diabetics, hypolipidemics.
* Adults unable to express their will.
* Not understanding French
* Patients participating in a clinical trial for a drug treatment.

Primary outcomes:
measure: Evaluation of the lipolytic response of adipocytes isolated from human visceral and subcutaneous adipose tissue to factors derived from cancer cells in acid environment by the glycerol measurement
timeFrame: Up to 100 days after the adipose tissue collection"
measure: Evaluation of the lipolytic response of adipocytes isolated from human visceral and subcutaneous adipose tissue to factors derived from cancer cells in acid environment by the fatty acid measurement.
timeFrame: Up to 100 days after the adipose tissue collection"
Secondary outcomes:
measure: Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by western-blot
timeFrame: Up to 2 years after the adipose tissue collection
measure: Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by ELISA
timeFrame: Up to 2 years after the adipose tissue collection
measure: Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by proteomic analyses
timeFrame: Up to 2 years after the adipose tissue collection
measure: Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by biochemical analyses
timeFrame: Up to 2 years after the adipose tissue collection
measure: Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by metabolomic analyses
timeFrame: Up to 2 years after the adipose tissue collection
measure: Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by RNA sequencing
timeFrame: Up to 2 years after the adipose tissue collection
measure: Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by RT-qPCR
timeFrame: Up to 2 years after the adipose tissue collection
Other outcomes:
Locations:
city: Brussel
country: Belgium
facility: Cliniques universitaires Saint Luc
Study officials:
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Benoit Navez, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lefevre C, Thibaut MM, Loumaye A, Thissen JP, Neyrinck AM, Navez B, Delzenne NM, Feron O, Bindels LB. Tumoral acidosis promotes adipose tissue depletion by fostering adipocyte lipolysis. Mol Metab. 2024 May;83:101930. doi: 10.1016/j.molmet.2024.101930. Epub 2024 Apr 1.