Ignite Creation Date:
2024-05-06 @ 8:02 PM
Last Modification Date:
2024-10-26 @ 3:19 PM
Study NCT ID:
NCT06236932
Status:
RECRUITING
Last Update Posted:
2024-02-01
First Post:
2024-01-04
Brief Title:
Susceptibility to Infectious Diseases in obEsity an endocRine trAnslational socioLogic Evaluation SIDERALE
Sponsor:
Federico II University
Organization:
Federico II University
Study Overview
Official Title:
PRIN SIDERALE Susceptibility to Infectious Diseases in obEsity an endocRine trAnslational socioLogic Evaluation
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SIDERALE2020
Brief Summary:
Obesity is a life-threatening disease defined by excessive fat accumulation that increases the risk of other diseases such as cardiovascular events hypertension diabetes and cancer Obesity is also a risk factor for nosocomial infections and is associated with worse COVID-19 outcomes although anthropometric measurements are not routinely recorded during hospitalization and lack of a registry data does not allow performing retrospective studiesObesity is closely related to chronodisruption characterized by deregulation of physiological and behavioral central and peripheral circadian rhythms contributing to the obesity-related metabolic impairment Eating and sleeping time schedules are relevant synchronizers of humans biological clock Several studies suggest a role of dietary interventions in rewiring the circadian rhythm with Mediterranean diet MD regulating nutritional patterns Moreover considering its positive impact on sleep quality melatonin intake was suggested as a potential regulator of circadian rhythms The relation between chronodisruption obesity and infections has not been investigated and a first proof of concept Pilot study will aim at investigating it Three cohorts of obese patients with different aetiology essential obesity obesity with type 2 diabetes genetic forms of obesity and a cohort of lipodystrophic patients will be enrolled in the study which is designed as a two-phases protocol During the first phase 0-12 weeks w patients will be subjected to dietary intervention with hypocaloric MD in a second phase 12-24w melatonin 1mgdie before sleep will be added to the hypocaloric MD The susceptibility to infections will be investigated through the evaluation of 1 the number of events - ie flu- or flulike syndromes skin respiratory digestive urinary infections-per patient of the 4 groups and the blood assays to detect the infection with Epstein-Barr Cytomegalovirus Varicella Measles and SARS-CoV-2 IgG and IgM hepatitis C and hepatitis B core antibodies and Quantiferon TB Gold 2 the clock genes rhythm and TLRs expression in patient immune cells at baseline 12w and 24wThe mutual relationship between biomedical values environmental and social conditions and lifestyle habits will be evaluated by structured questionnaires Validation of questionnaires to explore the susceptibility to infections is another delivery planned for the current study
Detailed Description:
The current project aims at investigating 1 the susceptibility to infectious disease in obese patients the role of tailored dietetic schemes of Mediterranean diet MD and melatonin supplementation on infective events 2 association of the oral andor gut microbiota signature with bacterial or viral infections in the above described obese cohorts 3 the mutual relationship between biomedical values environmental conditions and lifestyle habits through structured questionnaires and therefore the possible impact of this study on the National Health System NHS
The role of melatonin as chronobiologic influencer of circadian metabolic processes and as anti-obesogenic and weight-reducing effector comes to the fore in these last decades Moreover melatonin is also known to possess anti-inflammatory and antioxidant properties that may ameliorate the condition of low-grade chronic inflammation metaflammation observed in patients with obesity Nevertheless although there has been a tremendous interest in the role of the clock genes in regulating metabolic processes relatively less effort has been expended examining how the regulation of circadian rhythms and metabolic inputs can affect the susceptibility to infections To address this question Unit 1 will enroll patients with essential obesity 20 subjects BMI 30-35 Kgm2 and with genetic forms of obesity 20 subjects of both genders aged 18-65yrs to the main proof of concept pilot study
At baseline T0 patients will be subjected to anthropometric determinations including body weight and height for BMI calculation body composition by mean of DXA Scan blood serum and urine collection oral cavity swab and stool sampling Patients will undergo a session of behavioural dietary counselling by which patients will be educated to adhere to a hypocaloric MD for the first 12w T1 and to add to the MD the supplementation with 1mgdie of melatonin for other 12w T2 The same patients will be visited and subjected to the anthropometric determinations and biological samples at T0 T1 T2 of protocol The endpoints for Unit 1 will be 1to investigate the impact of tailored hypocaloric MD and hypocaloric MD plus melatonin supplement formulation 1mgdie before sleep on the number of events - ie flu- or flulike syndromes skin respiratory digestive urinary infections - per patient of the 4 groups recording the number of infectious events during the clinical examinations in six months and 1 year follow up and detect the SARS-CoV-2 Epstein-Barr Cytomegalovirus Varicella and Measles IgG and IgM hepatitis C and hepatitis B core antibodies and Quantiferon TB Gold QFT-GIT The obtained clinical results on infections events from the SIDERALE study will be used to formulate hypotheses for a prospective study and for the formulation of a specific validate questionnaire
2to assess the impact of a tailored hypocaloric MD and hypocaloric MD plus melatonin supplement formulation 1mgdie before sleep on anthropometric determinations glucose and lipid metabolism thyroid and adrenal axis leptin adiponectin IGFBP2 sirtuin 1 SIRT1 ESR high-sensitivity CRP fibrinogen and inflammatory cytokines TNF IL-6 IL-1Beta IL-18 and melatonin that will be evaluated at T0 T1 T2
3to assess the impact of a tailored hypocaloric MD and hypocaloric MD plus melatonin supplement formulation 1mgdie before sleep on the entrainment of circadian clock misalignment evaluating clock gene expression by RT-qPCR in peripheral blood mononuclear cells PBMC and concomitantly on the regulation of Toll like-receptors TLRs and suppressor cytokine signaling 3 SOCS3 known to play a crucial role in eliciting immunity and improving the well-known susceptibility to infections in patients with obesity all evaluated by RT-qPCR in PBMC of all patients cohorts at 8 am 12 pm and 12 am
4to quantify the impact of our intervention on the NHS in terms of decrease of antibiotic and antiviral treatment and ER emergency room admissions in six months and 1 year of follow up
Moreover an in vitro analysis will be performed on 3T3-L1 cells mouse pre-adipocytes 3T3-L1 differentiated in adipocytes will be synchronized and treated with melatonin in presence of TLRs agonists ie
lipopolysaccharide Pam3CSK ssRNA40 imiquimod Evaluation of TLRs signalling pathway will be performed by western blot Evaluation of inflammatory cytokines TNF IL-6 IL-1 IL-18 and chemokines MCP-1 CXCL5 will be performed by CLIA andor ELISA andor western blot
The role of melatonin as chronobiologic influencer of circadian metabolic processes and as anti-obesogenic and weight-reducing effector comes to the fore in these last decades Moreover melatonin is also known to possess anti-inflammatory and antioxidant properties that may ameliorate the condition of low-grade chronic inflammation metaflammation observed in patients with obesity Nevertheless although there has been a tremendous interest in the role of the clock genes in regulating metabolic processes relatively less effort has been expended examining how the regulation of circadian rhythms and metabolic inputs can affect the susceptibility to infections To address this question Unit 1 will enroll patients with essential obesity 20 subjects BMI 30-35 Kgm2 and with genetic forms of obesity 20 subjects of both genders aged 18-65yrs to the main proof of concept pilot study
At baseline T0 patients will be subjected to anthropometric determinations including body weight and height for BMI calculation body composition by mean of DXA Scan blood serum and urine collection oral cavity swab and stool sampling Patients will undergo a session of behavioural dietary counselling by which patients will be educated to adhere to a hypocaloric MD for the first 12w T1 and to add to the MD the supplementation with 1mgdie of melatonin for other 12w T2 The same patients will be visited and subjected to the anthropometric determinations and biological samples at T0 T1 T2 of protocol The endpoints for Unit 1 will be 1to investigate the impact of tailored hypocaloric MD and hypocaloric MD plus melatonin supplement formulation 1mgdie before sleep on the number of events - ie flu- or flulike syndromes skin respiratory digestive urinary infections - per patient of the 4 groups recording the number of infectious events during the clinical examinations in six months and 1 year follow up and detect the SARS-CoV-2 Epstein-Barr Cytomegalovirus Varicella and Measles IgG and IgM hepatitis C and hepatitis B core antibodies and Quantiferon TB Gold QFT-GIT The obtained clinical results on infections events from the SIDERALE study will be used to formulate hypotheses for a prospective study and for the formulation of a specific validate questionnaire
2to assess the impact of a tailored hypocaloric MD and hypocaloric MD plus melatonin supplement formulation 1mgdie before sleep on anthropometric determinations glucose and lipid metabolism thyroid and adrenal axis leptin adiponectin IGFBP2 sirtuin 1 SIRT1 ESR high-sensitivity CRP fibrinogen and inflammatory cytokines TNF IL-6 IL-1Beta IL-18 and melatonin that will be evaluated at T0 T1 T2
3to assess the impact of a tailored hypocaloric MD and hypocaloric MD plus melatonin supplement formulation 1mgdie before sleep on the entrainment of circadian clock misalignment evaluating clock gene expression by RT-qPCR in peripheral blood mononuclear cells PBMC and concomitantly on the regulation of Toll like-receptors TLRs and suppressor cytokine signaling 3 SOCS3 known to play a crucial role in eliciting immunity and improving the well-known susceptibility to infections in patients with obesity all evaluated by RT-qPCR in PBMC of all patients cohorts at 8 am 12 pm and 12 am
4to quantify the impact of our intervention on the NHS in terms of decrease of antibiotic and antiviral treatment and ER emergency room admissions in six months and 1 year of follow up
Moreover an in vitro analysis will be performed on 3T3-L1 cells mouse pre-adipocytes 3T3-L1 differentiated in adipocytes will be synchronized and treated with melatonin in presence of TLRs agonists ie
lipopolysaccharide Pam3CSK ssRNA40 imiquimod Evaluation of TLRs signalling pathway will be performed by western blot Evaluation of inflammatory cytokines TNF IL-6 IL-1 IL-18 and chemokines MCP-1 CXCL5 will be performed by CLIA andor ELISA andor western blot
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None