Clinical trial NCT05071391: Autophagy and Inflammasome in Obesity: Effect of Weight Loss and Potential Therapeutic Implications
Official title: Role of Autophagy and Inflammasome in the Pathophysiology of Obesity: Effect of Weight Loss and Potential Therapeutic Implications
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Keywords: bariatric surgery
autophagy
inflammasome
atherosclerosis
cardiovascular disease
Lead sponsor: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
name: Hospital Universitario Doctor Peset
First posted: 2021-10-08
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects with obesity prescribed bariatric surgery to treat their obesity and related comorbidities

Brief summary: The main aim of this project is to determine the implication of autophagy and inflammasome in the pathogenesis of obesity and related comorbidities, and to explore in depth the mechanisms associated with the activation of immune cells leading early stages of the atherosclerotic process and metabolic disease. The hypothesis of the present study is that weight loss mediated by Roux-en-Y gastric bypass (RYGB) improves the protein expression of markers of autophagy and inflammation within immune cells. Moreover, the investigators will explore the association of these mechanisms with the mitochondrial function and dynamics, Endoplasmic Reticulum (ER) stress an intracellular nutritional status of leukocytes (measured by fluorescence microscopy and western blot). Further, the potential relationship between changes in the mentioned intracellular pathways and systemic pathological mechanisms including oxidative stress, inflammation and glucose and lipid metabolism will be explored. Hence, serum carbonylated proteins, myeloperoxidase (MPO) levels, antioxidant enzymatic activities including SOD (Superoxide dismutase) and catalase, circulating cytokines, and glucose and lipid metabolism parameters will be evaluated in a cohort of obese subjects before and 12 months after RYGB intervention.


Eligibility criteria: Inclusion Criteria:

* Body Mass Index (BMI) ≥ 30 kg/m\^2
* duration of obesity over 5 years

Exclusion Criteria:

* history of drug abuse
* pregnancy or lactation
* neoplastic disease
* severe renal/hepatic disease
* history of cardiovascular disease
* chronic inflammatory disease
* secondary cause for obesity (hypothyroidism, Cushing's syndrome)

Primary outcomes:
measure: Changes in the protein expression of autophagy markers in leukocytes 12 months after the RYGB intervention
timeFrame: 12 months
measure: Changes in the relative protein expression of inflammatory mediators in leukocytes 12 months after the RYGB intervention
timeFrame: 12 months
Secondary outcomes:
measure: Changes in the protein expression of markers of mitochondrial dynamics and function in leukocytes 12 months after the RYGB intervention.
timeFrame: 12 months
measure: Changes in the protein expression of markers of nutrient sensing and ER stress in leukocytes 12 months after the RYGB intervention.
timeFrame: 12 months
measure: Changes in superoxide production 12 months after the RYGB intervention.
timeFrame: 12 months
measure: Changes in serum MPO levels 12 months after the RYGB intervention.
timeFrame: 12 months
measure: Changes in protein carbonylation in serum 12 months after the RYGB intervention.
timeFrame: 12 months
measure: Changes in serum SOD enzymatic activity 12 months after the RYGB intervention.
timeFrame: 12 months
measure: Changes in serum catalase enzymatic activity 12 months after the RYGB intervention.
timeFrame: 12 months
measure: Effect of the RYGB on body weight
timeFrame: 12 months
measure: Effect of the RYGB on Body Mass Index (BMI)
timeFrame: 12 months
measure: Effect of the RYGB on blood pressure
timeFrame: 12 months
measure: Effect of the RYGB on fasting Glucose levels
timeFrame: 12 months
measure: Effect of the RYGB on fasting Insulin levels
timeFrame: 12 months
measure: Effect of the RYGB on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Index
timeFrame: 12 months
measure: Effect of the RYGB on glycated hemoglobin (HbA1c)
timeFrame: 12 months
measure: Effect of the RYGB on Total Cholesterol (TC)
timeFrame: 12 months
measure: Effect of the RYGB on High Density Lipoprotein Cholesterol (HDLc) levels
timeFrame: 12 months
measure: Effect of the RYGB on Low Density Lipoprotein Cholesterol (LDLc) levels
timeFrame: 12 months
measure: Effect of the RYGB on Triglyceride (TG) levels
timeFrame: 12 months
measure: Effect of the RYGB on high sensitivity C-Reactive Protein (hsCRP) levels
timeFrame: 12 months
measure: Effect of the RYGB on Interleukin-6 (IL6) levels
timeFrame: 12 months
measure: Effect of the RYGB on Interleukin-1 β (IL1β) levels
timeFrame: 12 months
measure: Remission rate for pathologies related to metabolic syndrome 12 months after RYGB intervention
timeFrame: 12 months
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
Study officials:
affiliation: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
name: Milagros Rocha Barajas, PhD
role: PRINCIPAL_INVESTIGATOR
References: