Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05761145 |
| Other study ID # |
01C126 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 15, 2021 |
| Est. completion date |
March 23, 2022 |
Study information
| Verified date |
March 2023 |
| Source |
Istituto Auxologico Italiano |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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, i.e. 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 (e.g., atherogenesis,
thromboembolism, arterial hypertension, insulin resistance, low-grade chronic
inflammation, etc.), could phenotypically identify patients with increased
cardiovascular risk (e.g., 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
(plasma/erythrocyte/platelet/leukocyte) and gene regulators (WAT/BAT-related) which, with
sensitivity and specificity, is associated with diagnosis of metabolic syndrome.
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 kg/m2), 30 obese without metabolic syndrome (age:
18-35 years; BMI > 35 kg/m2) and 30 obese with metabolic syndrome (age: 18-35 years; BMI > 35
kg/m2), according to the 2009 IDF criteria. Subjects of normal weight will be recruited from
medical/paramedical 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 (C18:1 and C24:1), the
sphingomyelins (those from C16 to C24 and the one C24:1), 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 RT/PCR technique, the
leukocyte mRNA levels of the following genes will be determined: Cidea, Hoxc9 and Cpt1a.
