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

NCT06236932 | Recruiting DMC

• 1 other identifier: PRIN SIDERALE
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

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 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

Keywords

Obesity; Infections; Melatonin; Mediterranean Diet; Gut microbiota; Chronobiology

Outcome Measures

Primary Outcomes (1)

• Investigation of the impact of hypocaloric MD and hypocaloric MD plus melatonin on the number of events - i.e. flu- or flulike syndromes, skin, respiratory, digestive, urinary infections in patients with obesity and lipodystrophy

  The primary outcome will be: to investigate the impact of tailored hypocaloric MD and hypocaloric MD plus melatonin (supplement formulation, 1mg/die before sleep) on the number of events - i.e. flu- or flulike syndromes, skin, respiratory, digestive, urinary infections - per all patients, recording the number of infectious events,trough specific surveys, during the clinical and biochemical 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).

  Change from baseline at 3-6-12 months

Secondary Outcomes (42)

• Change in body weight (kg) after hypocaloric MD and hypocaloric MD plus melatonin in patients with obesity and lipodystrophy.

  Change from baseline at 3-6-12 months

• BMI modification after hypocaloric MD and hypocaloric MD plus melatonin in patients with obesity and lipodystrophy: body weight (kg) will be combined with height (m) to obtain BMI (kg/m^2)

  Change from baseline at 3-6-12 months

• Change in waist and hip circumference after hypocaloric MD and hypocaloric MD plus melatonin in patients with obesity and lipodystrophy.

  Change from baseline at 3-6-12 months

• Change in body composition assessed by Bioelectrical impedance analysis (BIA) after hypocaloric MD and hypocaloric MD plus melatonin in patients with obesity and lipodystrophy .

  Change from baseline at 3-6-12 months

• Change in body composition assessed by DXA scan after hypocaloric MD and hypocaloric MD plus melatonin in patients with obesity and lipodystrophy.

  Change from baseline at 3-6-12 months

Study Arms (2)

Mediterranean diet group

ACTIVE COMPARATOR

At baseline (T0), all 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).

Dietary Supplement: Mediterranean diet

Mediterranean diet plus melatonin group

ACTIVE COMPARATOR

After the first 12 w of the study (T2), all patients will continue a hypocaloric MD adding the supplementation with 1mg/die of melatonin before bedtime for other 12w.

Dietary Supplement: Mediterranean diet; Dietary Supplement: Melatonin supplementation

Interventions

Mediterranean diet DIETARY_SUPPLEMENT

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).

Mediterranean diet group; Mediterranean diet plus melatonin group

Melatonin supplementation DIETARY_SUPPLEMENT

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

Mediterranean diet plus melatonin group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• essential obesity (BMI : 30-35 Kg/m2)
• genetic forms of obesity (BMI: 30-35 Kg/m2)
• obesity (BMI:30-35 Kg/m2) associated with T2DM
• obesity (BMI:30-35 Kg/m2) associated with endocrinopathies
• lipodystrophy

You may not qualify if:

• pregnancy, breast-feeding, alcohol and drug abuse, known severe haematological, cardiac, liver, kidney, mental diseases, hypogonadisms, hormonal treatments including estroprogestins, intolerance to melatonin or excipients

Sponsors & Collaborators

• Federico II University: lead
• University of Roma La Sapienza: collaborator
• University of Pisa: collaborator
• Università degli Studi del Piemonte Orientale Amedeo Avogadro: collaborator
• University of Rome Foro Italico: collaborator

Study Sites (4)

"Federico II" University of Naples, Department of Clinical and Molecular Endocrinology and Oncology

Naples, 80131, Italy

RECRUITING

Università del Piemonte Orientale

Novara, 28100, Italy

RECRUITING

University of Pisa

Pisa, 56126, Italy

RECRUITING

"Sapienza" University of Rome

Roma, 00161, Italy

RECRUITING

Related Publications (10)

• Leitner DR, Fruhbeck G, Yumuk V, Schindler K, Micic D, Woodward E, Toplak H. Obesity and Type 2 Diabetes: Two Diseases with a Need for Combined Treatment Strategies - EASO Can Lead the Way. Obes Facts. 2017;10(5):483-492. doi: 10.1159/000480525. Epub 2017 Oct 12.

  PMID: 29020674 BACKGROUND

• Barrea L, Muscogiuri G, Frias-Toral E, Laudisio D, Pugliese G, Castellucci B, Garcia-Velasquez E, Savastano S, Colao A. Nutrition and immune system: from the Mediterranean diet to dietary supplementary through the microbiota. Crit Rev Food Sci Nutr. 2021;61(18):3066-3090. doi: 10.1080/10408398.2020.1792826. Epub 2020 Jul 21.

  PMID: 32691606 RESULT

• Brown RJ, Araujo-Vilar D, Cheung PT, Dunger D, Garg A, Jack M, Mungai L, Oral EA, Patni N, Rother KI, von Schnurbein J, Sorkina E, Stanley T, Vigouroux C, Wabitsch M, Williams R, Yorifuji T. The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline. J Clin Endocrinol Metab. 2016 Dec;101(12):4500-4511. doi: 10.1210/jc.2016-2466. Epub 2016 Oct 6.

  PMID: 27710244 RESULT

• Ceccarini G, Pelosini C, Ferrari F, Magno S, Vitti J, Salvetti G, Moretto C, Marioni A, Buccianti P, Piaggi P, Maffei M, Santini F. Serum IGF-binding protein 2 (IGFBP-2) concentrations change early after gastric bypass bariatric surgery revealing a possible marker of leptin sensitivity in obese subjects. Endocrine. 2019 Jul;65(1):86-93. doi: 10.1007/s12020-019-01915-y. Epub 2019 Apr 3.

  PMID: 30945111 RESULT

• Chu Y, Yang J, Shi J, Zhang P, Wang X. Obesity is associated with increased severity of disease in COVID-19 pneumonia: a systematic review and meta-analysis. Eur J Med Res. 2020 Dec 2;25(1):64. doi: 10.1186/s40001-020-00464-9.

  PMID: 33267871 RESULT

• Pivonello C, Negri M, Patalano R, Amatrudo F, Monto T, Liccardi A, Graziadio C, Muscogiuri G, Pivonello R, Colao A. The role of melatonin in the molecular mechanisms underlying metaflammation and infections in obesity: A narrative review. Obes Rev. 2022 Mar;23(3):e13390. doi: 10.1111/obr.13390. Epub 2021 Dec 3.

  PMID: 34861097 RESULT

• Scheithauer TPM, Rampanelli E, Nieuwdorp M, Vallance BA, Verchere CB, van Raalte DH, Herrema H. Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes. Front Immunol. 2020 Oct 16;11:571731. doi: 10.3389/fimmu.2020.571731. eCollection 2020.

  PMID: 33178196 RESULT

• Turk Wensveen T, Gasparini D, Rahelic D, Wensveen FM. Type 2 diabetes and viral infection; cause and effect of disease. Diabetes Res Clin Pract. 2021 Feb;172:108637. doi: 10.1016/j.diabres.2020.108637. Epub 2021 Jan 13.

  PMID: 33352263 RESULT

• Watanabe M, Caruso D, Tuccinardi D, Risi R, Zerunian M, Polici M, Pucciarelli F, Tarallo M, Strigari L, Manfrini S, Mariani S, Basciani S, Lubrano C, Laghi A, Gnessi L. Visceral fat shows the strongest association with the need of intensive care in patients with COVID-19. Metabolism. 2020 Oct;111:154319. doi: 10.1016/j.metabol.2020.154319. Epub 2020 Jul 23.

  PMID: 32712222 RESULT

• Genoni G, Prodam F, Marolda A, Giglione E, Demarchi I, Bellone S, Bona G. Obesity and infection: two sides of one coin. Eur J Pediatr. 2014 Jan;173(1):25-32. doi: 10.1007/s00431-013-2178-1. Epub 2013 Oct 22.

  PMID: 24146165 RESULT

MeSH Terms

Conditions

Obesity; Lipodystrophy; Infections

Interventions

Diet, Mediterranean

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Annamaria Colao, Prof

  Federico II University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Annamaria Colao, Prof

CONTACT

+393285390000; colao@unina.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Prof.

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: February 1, 2024
• Study Start: December 29, 2023
• Primary Completion: October 29, 2025
• Study Completion (Estimated): October 29, 2026
• Last Updated: August 12, 2025

Record last verified: 2025-08

Locations

IT (4)