Susceptibility to Infectious Diseases in obEsity: an endocRine trAnslational socioLogic Evaluation, "SIDERALE"

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 studies.Obesity 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 1mg/die 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 - i.e. 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 24w.The 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.

Conditions

• Obesity
• Type2diabetes
• Lipodystrophy
• Infections
• Obesity Associated Disorder

Interventions

DIETARY_SUPPLEMENT

Mediterranean diet

Hypocaloric Mediterranean Diet consist of a nutritional regimen with customized daily energy intake, calculated considering the Basal Metabolism and Physical Activity Level (LAF) of each patient. The distribution of macronutrients will be worked out as follows: ≃ 55-60% Carbohydrates (of which 80% are complex carbohydrates, pasta, bread, rice, whole grains and 20% simple sugars), ≃ 10-15% Proteins (of which the 60% of animal origin (meat, especially white) and 40% of vegetable origin (beans, chickpeas, lentils and legumes in general), ≃ 25-30% of lipids (predominantly olive oil).

DIETARY_SUPPLEMENT

Melatonin supplementation

Melatonin (supplement formulation in capsules, 1mg/die one hour before sleep) will be associated with mediterranean diet for 12 w.

Sponsors & Collaborators

• University of Roma La Sapienza

  collaborator OTHER

• University of Pisa

  collaborator OTHER

• Università degli Studi del Piemonte Orientale Amedeo Avogadro

  collaborator OTHER

• University of Rome Foro Italico

  collaborator OTHER

• Federico II University

  lead OTHER

Principal Investigators

• Annamaria Colao, Prof · Federico II University

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-29

Primary Completion

2025-10-29

Completion

2026-10-29

Countries

• Italy

Study Locations