ObesityNCT05071391
Autophagy and Inflammasome in Obesity: Effect of Weight Loss and Potential Therapeutic Implications
An observational study of Obesity, run by Milagros Rocha Barajas at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Obesity
- What is being tested?
- Roux-en-Y gastric bypass
- Type of treatment
- Surgery or procedure
- How many people
- 45 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jan 2017to 31 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects with obesity prescribed bariatric surgery to treat their obesity and related comorbidities
Who may be able to join
- Body Mass Index (BMI) ≥ 30 kg/m^2
- duration of obesity over 5 years
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Autophagy and Inflammasome in the Pathophysiology of 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.
- Conditions
- Obesity
- Being tested
- Roux-en-Y gastric bypass
- Keywords
- bariatric surgery, autophagy, inflammasome, atherosclerosis, cardiovascular disease
- Medical subject headings
- Obesity, Atherosclerosis, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Roux-en-Y gastric bypassProcedure or surgery
Also called RYGB
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.
| Study group | Role | What they receive |
|---|---|---|
| Obese | Obese patients undergoing Roux-en-Y gastric bypass Receives: Procedure: Roux-en-Y gastric bypass |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the protein expression of autophagy markers in leukocytes 12 months after the RYGB intervention
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.
Measured: 12 months
Changes in the relative protein expression of inflammatory mediators in leukocytes 12 months after the RYGB intervention
Relative expression of intracellular proteins related to inflammatory pathways (MCP1, NF-kB) assessed by western blot and normalized to the loading control protein.
Measured: 12 months
Secondary outcomes (22)
Changes in the protein expression of markers of mitochondrial dynamics and function in leukocytes 12 months after the RYGB intervention.
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.
Measured: 12 months
Changes in the protein expression of markers of nutrient sensing and ER stress in leukocytes 12 months after the RYGB intervention.
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.
Measured: 12 months
Changes in superoxide production 12 months after the RYGB intervention.
Evaluation of superoxide production in leukocytes by means of fluorescence dye (Relative Fluorescence Units) as contributor to pro-oxidant processes.
Measured: 12 months
Changes in serum MPO levels 12 months after the RYGB intervention.
Evaluation of serum levels of the prooxidant MPO by immunoassay ELISA (ng/mL) as contributor to pro-oxidant and pro-inflammatory processes.
Measured: 12 months
Changes in protein carbonylation in serum 12 months after the RYGB intervention.
Evaluation of carbonyl groups in serum proteins by means of immunoassay ELISA (nmol/mg protein) as a marker of systemic oxidative damage.
Measured: 12 months
Changes in serum SOD enzymatic activity 12 months after the RYGB intervention.
Evaluation of SOD enzymatic activity in serum (nmol/min/mL) as part of the systemic antioxidant defense system.
Measured: 12 months
Changes in serum catalase enzymatic activity 12 months after the RYGB intervention.
Evaluation of catalase enzymatic activity in serum (nmol/min/mL) as part of the systemic antioxidant defense system.
Measured: 12 months
Effect of the RYGB on body weight
Changes in the body weight (kg) of patients 12 months after the RYGB intervention determined with an electronic scale
Measured: 12 months
Effect of the RYGB on Body Mass Index (BMI)
Changes in the BMI (kg/m^2) of patients 12 months after the RYGB intervention, measure by the formula: weight (kg) / [height (m)]^2
Measured: 12 months
Effect of the RYGB on blood pressure
Changes in Systolic/Diastolic Blood Pressure levels (SBP/DBP) (mmHg) measured with a sphygmomanometer
Measured: 12 months
Effect of the RYGB on fasting Glucose levels
Changes in fasting Glucose (mg/dL) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism
Measured: 12 months
Effect of the RYGB on fasting Insulin levels
Changes in fasting Insulin (μU/mL) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism
Measured: 12 months
Effect of the RYGB on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Index
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
Measured: 12 months
Effect of the RYGB on glycated hemoglobin (HbA1c)
Changes in HbA1c (%) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism
Measured: 12 months
Effect of the RYGB on Total Cholesterol (TC)
Changes in TC (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Measured: 12 months
Effect of the RYGB on High Density Lipoprotein Cholesterol (HDLc) levels
Changes in HDLc (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Measured: 12 months
Effect of the RYGB on Low Density Lipoprotein Cholesterol (LDLc) levels
Changes in LDLc (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Measured: 12 months
Effect of the RYGB on Triglyceride (TG) levels
Changes in TG (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Measured: 12 months
Effect of the RYGB on high sensitivity C-Reactive Protein (hsCRP) levels
Changes in hsCRP (mg/L) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation
Measured: 12 months
Effect of the RYGB on Interleukin-6 (IL6) levels
Changes in IL6 (pg/mL) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation
Measured: 12 months
Effect of the RYGB on Interleukin-1 β (IL1β) levels
Changes in IL1β (pg/mL) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation
Measured: 12 months
Remission rate for pathologies related to metabolic syndrome 12 months after RYGB intervention
Percentage of cases of remission for hypertension, hyperlipidemia and type 2 diabetes (T2D) after the intervention.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2021
- Study start1 Jan 2017
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milagros Rocha Barajas
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Salud Carlos III, Hospital Universitario Doctor Peset
- Responsible party
- Sponsor-investigator, Milagros Rocha Barajas, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
- Investigators
- Milagros Rocha Barajas, PhD, Principal investigator, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05071391
- Sponsor's protocol ID
- PI16/00301
- Status last verified
- Sep 2021
- First submitted
- 16 Sep 2021
- Last updated
- 8 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Autophagy and Inflammasome in the Pathophysiology of Obesity: Effect of Weight Loss and Potential Therapeutic Implications
- ClinicalTrials.gov ID
- NCT05071391
- Acronym / sponsor ID
- PI16/00301
- Conditions
- Obesity
- Keywords
- bariatric surgery, autophagy, inflammasome, atherosclerosis, cardiovascular disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Milagros Rocha BarajasUniversity, hospital or other
- Collaborators
- Instituto de Salud Carlos III, Hospital Universitario Doctor Peset
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 8 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Obese | – | Procedure: Roux-en-Y gastric bypassObese patients undergoing Roux-en-Y gastric bypass |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects with obesity prescribed bariatric surgery to treat their obesity and related comorbidities
Key inclusion criteria (2 listed)
- Body Mass Index (BMI) ≥ 30 kg/m^2
- duration of obesity over 5 years
Key exclusion criteria (7 listed)
- history of drug abuse
- pregnancy or lactation
- neoplastic disease
- severe renal/hepatic disease
- history of cardiovascular disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Roux-en-Y gastric bypassAlso: RYGBGastric 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. | Procedure or surgery | Obese |
Primary outcome
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.
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.
22 secondary outcomes
Changes in the protein expression of markers of mitochondrial dynamics and function in leukocytes 12 months after the RYGB intervention.
Time frame: 12 months
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
Changes in superoxide production 12 months after the RYGB intervention.
Time frame: 12 months
Changes in serum MPO levels 12 months after the RYGB intervention.
Time frame: 12 months
Changes in protein carbonylation in serum 12 months after the RYGB intervention.
Time frame: 12 months
Changes in serum SOD enzymatic activity 12 months after the RYGB intervention.
Time frame: 12 months
Changes in serum catalase enzymatic activity 12 months after the RYGB intervention.
Time frame: 12 months
Effect of the RYGB on body weight
Time frame: 12 months
Effect of the RYGB on Body Mass Index (BMI)
Time frame: 12 months
Effect of the RYGB on blood pressure
Time frame: 12 months
Effect of the RYGB on fasting Glucose levels
Time frame: 12 months
Effect of the RYGB on fasting Insulin levels
Time frame: 12 months
Effect of the RYGB on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Index
Time frame: 12 months
Effect of the RYGB on glycated hemoglobin (HbA1c)
Time frame: 12 months
Effect of the RYGB on Total Cholesterol (TC)
Time frame: 12 months
Effect of the RYGB on High Density Lipoprotein Cholesterol (HDLc) levels
Time frame: 12 months
Effect of the RYGB on Low Density Lipoprotein Cholesterol (LDLc) levels
Time frame: 12 months
Effect of the RYGB on Triglyceride (TG) levels
Time frame: 12 months
Effect of the RYGB on high sensitivity C-Reactive Protein (hsCRP) levels
Time frame: 12 months
Effect of the RYGB on Interleukin-6 (IL6) levels
Time frame: 12 months
Effect of the RYGB on Interleukin-1 β (IL1β) levels
Time frame: 12 months
Remission rate for pathologies related to metabolic syndrome 12 months after RYGB intervention
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Milagros Rocha Barajas, PhD principal investigator
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity, run by Milagros Rocha Barajas at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the protein expression of autophagy markers in leukocytes 12 months after the RYGB intervention (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021.