Ignite Creation Date:
2024-05-06 @ 6:43 PM
Last Modification Date:
2024-10-26 @ 2:53 PM
Study NCT ID:
NCT05761145
Status:
COMPLETED
Last Update Posted:
2023-03-13
First Post:
2023-02-27
Brief Title:
Sphingo-lipotoxicity and Trans-differentiation of Adipose Tissue in Obesity SFINGOTRANS
Sponsor:
Istituto Auxologico Italiano
Organization:
Istituto Auxologico Italiano
Study Overview
Official Title:
Relationship Between Sphingo-lipotoxicity and Trans-differentiation of Adipose Tissue Cross-sectional Study in Subjects With Different Dysmetabolic Severity
Status:
COMPLETED
Status Verified Date:
2023-03
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:
SFINGOTRANS
Brief Summary:
After recruiting a population of subjects with different metabolic severity subjects of normal weight and obese patients with and without metabolic syndrome the objectives of the present research will be
1 determine leukocyte mRNA levels of Cidea gene associated with BAT functional status Hoxc9 gene associated with browning of WAT and Cpt1a gene associated with β-oxidation of fatty acids in both tissues ie BAT and WAT secondary endpoint
2 to determine energy expenditure with indirect calorimetric technique body temperature and circulating catecholamine levels which will be correlated to leukocyte levels of Cidea Hoxc9 and Cpt1a mRNA secondary endpoint
3 determine the plasma levels of an extensive panel of sphingolipids including in particular ceramides and sphingosine-1-phosphate which by exerting a lipotoxic lipoinflammatory and anti-adipogenic effect will be correlated to the leukocyte levels of Cidea Hoxc9 mRNA and Cpt1a primary endpoint
4 determine the erythrocyte leukocyte and platelet levels of sphingolipids which acting as peripheral biomarkers of cardiometabolic dysfunction eg atherogenesis thromboembolism arterial hypertension insulin resistance low-grade chronic inflammation etc could phenotypically identify patients with increased cardiovascular risk eg obese patients with or without metabolic syndrome secondary endpoint
Hypothesis the existence of a relationship between sphingohypotoxicity and transdifferentiation of adipose tissue and a combination of sphingolipids plasmaerythrocyteplateletleukocyte and gene regulators WATBAT-related which with sensitivity and specificity is associated with diagnosis of metabolic syndrome
1 determine leukocyte mRNA levels of Cidea gene associated with BAT functional status Hoxc9 gene associated with browning of WAT and Cpt1a gene associated with β-oxidation of fatty acids in both tissues ie BAT and WAT secondary endpoint
2 to determine energy expenditure with indirect calorimetric technique body temperature and circulating catecholamine levels which will be correlated to leukocyte levels of Cidea Hoxc9 and Cpt1a mRNA secondary endpoint
3 determine the plasma levels of an extensive panel of sphingolipids including in particular ceramides and sphingosine-1-phosphate which by exerting a lipotoxic lipoinflammatory and anti-adipogenic effect will be correlated to the leukocyte levels of Cidea Hoxc9 mRNA and Cpt1a primary endpoint
4 determine the erythrocyte leukocyte and platelet levels of sphingolipids which acting as peripheral biomarkers of cardiometabolic dysfunction eg atherogenesis thromboembolism arterial hypertension insulin resistance low-grade chronic inflammation etc could phenotypically identify patients with increased cardiovascular risk eg obese patients with or without metabolic syndrome secondary endpoint
Hypothesis the existence of a relationship between sphingohypotoxicity and transdifferentiation of adipose tissue and a combination of sphingolipids plasmaerythrocyteplateletleukocyte and gene regulators WATBAT-related which with sensitivity and specificity is associated with diagnosis of metabolic syndrome
Detailed Description:
Materials and methods Patients 90 adults of both sexes will be recruited of whom 30 of normal weight age 18-50 years BMI 25 kgm2 30 obese without metabolic syndrome age 18-35 years BMI 35 kgm2 and 30 obese with metabolic syndrome age 18-35 years BMI 35 kgm2 according to the 2009 IDF criteria Subjects of normal weight will be recruited from medicalparamedical staff while obese patients from hospitalized at the Division of Metabolic Diseases Istituto Auxologico Italiano Piancavallo VB Italy for a 3-week multidisciplinary weight reduction program BWRP which includes low-calorie diet physical exercise psychological support and nutrition education
Subjects with other pathologies other than obesity will be excluded from the study including those treated with anticoagulant and antiplatelet drugs since the evaluation of intraplatelet levels of sphingolipids will be foreseen
In basal conditions the main anthropometric data will be collected weight height waist circumference hip circumference BMI body composition will be evaluated with a bioimpedance technique the main cardiovascular parameters will be recorded blood pressure and heart rate a calorimetric examination will be performed collection of body temperature morning and evening request of the environmental temperature to which one is generally exposed during the day and determined with automated clinical biochemistry techniques the following biochemical parameters glucose total cholesterol triglycerides LDL HDL fatty acids non-esterified insulin glycated Hb catecholamines and C-reactive protein
Determination of the lipidomic profile in plasma and cell extracts A lipidomics will be performed in plasma and in cellular extracts from erythrocytes leukocytes and platelets The levels of the individual analytes will be determined with a technologically advanced analytical instrumentation consisting of a triple quadruple hybrid mass spectrometer with linear ion trap QTRAP 5500 AB Sciex interfaced with an ultra-high performance liquid chromatograph UHPLC
Plasma and cellular levels of the following sphingolipids will be measured ceramides and dihydroceramides from C16 to C24 including 2 unsaturated ones C181 and C241 the sphingomyelins those from C16 to C24 and the one C241 sphingosine sphinganine sphingosine-1-phosphate and sphinganine-1-phosphate
Determination of leukocyte mRNA levels of gene regulators From an aliquot containing leukocytes stored ad hoc the total mRNA will be extracted and with RTPCR technique the leukocyte mRNA levels of the following genes will be determined Cidea Hoxc9 and Cpt1a
Subjects with other pathologies other than obesity will be excluded from the study including those treated with anticoagulant and antiplatelet drugs since the evaluation of intraplatelet levels of sphingolipids will be foreseen
In basal conditions the main anthropometric data will be collected weight height waist circumference hip circumference BMI body composition will be evaluated with a bioimpedance technique the main cardiovascular parameters will be recorded blood pressure and heart rate a calorimetric examination will be performed collection of body temperature morning and evening request of the environmental temperature to which one is generally exposed during the day and determined with automated clinical biochemistry techniques the following biochemical parameters glucose total cholesterol triglycerides LDL HDL fatty acids non-esterified insulin glycated Hb catecholamines and C-reactive protein
Determination of the lipidomic profile in plasma and cell extracts A lipidomics will be performed in plasma and in cellular extracts from erythrocytes leukocytes and platelets The levels of the individual analytes will be determined with a technologically advanced analytical instrumentation consisting of a triple quadruple hybrid mass spectrometer with linear ion trap QTRAP 5500 AB Sciex interfaced with an ultra-high performance liquid chromatograph UHPLC
Plasma and cellular levels of the following sphingolipids will be measured ceramides and dihydroceramides from C16 to C24 including 2 unsaturated ones C181 and C241 the sphingomyelins those from C16 to C24 and the one C241 sphingosine sphinganine sphingosine-1-phosphate and sphinganine-1-phosphate
Determination of leukocyte mRNA levels of gene regulators From an aliquot containing leukocytes stored ad hoc the total mRNA will be extracted and with RTPCR technique the leukocyte mRNA levels of the following genes will be determined Cidea Hoxc9 and Cpt1a
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?:
None
Is an FDA AA801 Violation?:
None