Skip to main content
OpenTrials
Completed

NCT Number: NCT05071391

Autophagy and Inflammasome in Obesity: Effect of Weight Loss and Potential Therapeutic Implications

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Obesity Arterial Occlusive Diseases Arteriosclerosis Atherosclerosis Body Weight Cardiovascular Diseases Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms Vascular Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Roux-en-Y gastric bypass

Procedure

Gastric bypass, also called Roux-en-Y gastric bypass, is a type of weight-loss surgery that involves creating a small pouch from the stomach and connecting the newly created pouch directly to the small intestine. After gastric bypass, swallowed food will go into this small pouch of stomach and then directly into the small intestine, thereby bypassing most of your stomach and the first section of your small intestine.

Gastric bypass is one of the most commonly performed types of bariatric surgery. Gastric bypass is done when diet and exercise haven't worked or when you have serious health problems because of your weight.

Other names: RYGB

Primary outcomes

  1. Changes in the protein expression of autophagy markers in leukocytes 12 months after the RYGB intervention

    Time frame: 12 months

    Relative expression of intracellular proteins related autophagy/mitophagy mechanisms (Beclin 1, ATG5, LC3II/I, NRB1, PINK1, MIEAP) assessed by western blot and normalized to the loading control protein.

  2. Changes in the relative protein expression of inflammatory mediators in leukocytes 12 months after the RYGB intervention

    Time frame: 12 months

    Relative expression of intracellular proteins related to inflammatory pathways (MCP1, NF-kB) assessed by western blot and normalized to the loading control protein.

Secondary outcomes

  1. Changes in the protein expression of markers of mitochondrial dynamics and function in leukocytes 12 months after the RYGB intervention.

    Time frame: 12 months

    Relative expression of proteins related to mitochondrial dynamics and function (OPA1, FIS1, MFN1, DRP1, MFN2, OXPHOS Complex, MTTFA, PGC1α, NRF1, BNIP3) assessed by western blot and normalized to the loading control protein. Changes in mitochondrial membrane potential of leukocytes after the intervention assessed by fluorescence dye TMRM.

  2. Changes in the protein expression of markers of nutrient sensing and ER stress in leukocytes 12 months after the RYGB intervention.

    Time frame: 12 months

    Relative expression of proteins related to nutritional status, metabolism and Endoplasmic Reticulum (ER) stress (AMPK, SIRT1, ATF6, CHOP) assessed by western blot and normalized to the loading control protein.

  3. Changes in superoxide production 12 months after the RYGB intervention.

    Time frame: 12 months

    Evaluation of superoxide production in leukocytes by means of fluorescence dye (Relative Fluorescence Units) as contributor to pro-oxidant processes.

  4. Changes in serum MPO levels 12 months after the RYGB intervention.

    Time frame: 12 months

    Evaluation of serum levels of the prooxidant MPO by immunoassay ELISA (ng/mL) as contributor to pro-oxidant and pro-inflammatory processes.

  5. Changes in protein carbonylation in serum 12 months after the RYGB intervention.

    Time frame: 12 months

    Evaluation of carbonyl groups in serum proteins by means of immunoassay ELISA (nmol/mg protein) as a marker of systemic oxidative damage.

  6. Changes in serum SOD enzymatic activity 12 months after the RYGB intervention.

    Time frame: 12 months

    Evaluation of SOD enzymatic activity in serum (nmol/min/mL) as part of the systemic antioxidant defense system.

  7. Changes in serum catalase enzymatic activity 12 months after the RYGB intervention.

    Time frame: 12 months

    Evaluation of catalase enzymatic activity in serum (nmol/min/mL) as part of the systemic antioxidant defense system.

  8. Effect of the RYGB on body weight

    Time frame: 12 months

    Changes in the body weight (kg) of patients 12 months after the RYGB intervention determined with an electronic scale

  9. Effect of the RYGB on Body Mass Index (BMI)

    Time frame: 12 months

    Changes in the BMI (kg/m^2) of patients 12 months after the RYGB intervention, measure by the formula: weight (kg) / [height (m)]^2

  10. Effect of the RYGB on blood pressure

    Time frame: 12 months

    Changes in Systolic/Diastolic Blood Pressure levels (SBP/DBP) (mmHg) measured with a sphygmomanometer

  11. Effect of the RYGB on fasting Glucose levels

    Time frame: 12 months

    Changes in fasting Glucose (mg/dL) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism

  12. Effect of the RYGB on fasting Insulin levels

    Time frame: 12 months

    Changes in fasting Insulin (μU/mL) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism

  13. Effect of the RYGB on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Index

    Time frame: 12 months

    Changes in HOMA-IR Index of patients 12 months after the RYGB intervention, measured with the formula: [Fasting Glucose (mg/dL) x Fasting Insulin (μU/mL)]/405, as a marker of glucose metabolism

  14. Effect of the RYGB on glycated hemoglobin (HbA1c)

    Time frame: 12 months

    Changes in HbA1c (%) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism

  15. Effect of the RYGB on Total Cholesterol (TC)

    Time frame: 12 months

    Changes in TC (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile

  16. Effect of the RYGB on High Density Lipoprotein Cholesterol (HDLc) levels

    Time frame: 12 months

    Changes in HDLc (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile

  17. Effect of the RYGB on Low Density Lipoprotein Cholesterol (LDLc) levels

    Time frame: 12 months

    Changes in LDLc (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile

  18. Effect of the RYGB on Triglyceride (TG) levels

    Time frame: 12 months

    Changes in TG (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile

  19. Effect of the RYGB on high sensitivity C-Reactive Protein (hsCRP) levels

    Time frame: 12 months

    Changes in hsCRP (mg/L) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation

  20. Effect of the RYGB on Interleukin-6 (IL6) levels

    Time frame: 12 months

    Changes in IL6 (pg/mL) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation

  21. Effect of the RYGB on Interleukin-1 β (IL1β) levels

    Time frame: 12 months

    Changes in IL1β (pg/mL) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation

  22. Remission rate for pathologies related to metabolic syndrome 12 months after RYGB intervention

    Time frame: 12 months

    Percentage of cases of remission for hypertension, hyperlipidemia and type 2 diabetes (T2D) after the intervention.

Sponsors and collaborators

Lead sponsor

Milagros Rocha Barajas

Other

Collaborators

  • Hospital Universitario Doctor Peset
  • Instituto de Salud Carlos III

Registry information

Official study title

Role of Autophagy and Inflammasome in the Pathophysiology of Obesity: Effect of Weight Loss and Potential Therapeutic Implications

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Oct 8, 2021
Registry last updated
Oct 8, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.