Clinical trial NCT06529913: Environmental Exposure to Heavy Metals, Nanoparticles, and Emergent Contaminants and Risk of Allergic Diseases
Official title: Model of diseAses Related to Environmental Exposure to Heavy meTals, nanopaRticles and Emergent Contaminants, Using a dIgital platfOrm of Clinical and Bio-humoral Data: the Way to Susceptibility/RisK BiomArker [MATRIOSKA Study] - The Seed.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Allergic Contact Dermatitis
Metal Allergy
Food Allergy
Nickel Sensitivity
Nickel; Eczema
Aluminum Allergy
Chromium; Eczema
Functional Gastrointestinal Disorders
Respiratory Injury
Pollution; Exposure
Pollution Related Respiratory Disorder
Environmental Exposure
Environment Related Disease
Environmental Illness
Oxidative Stress
Risk Reduction
Keywords: Metal Allergy
Nanoparticles
Emergent contaminants
Nickel
Aluminium
Copper
Chromium
Cobalt
Palladium
Titanium
Allergic Contact Dermatitis
Food Allergy
Functional Gastrointestinal Disorders
Respiratory Injury
Environmental Exposure
Patch test
Biomarkers
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
Collaborators: name: University of Bologna
First posted: 2024-07-31
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The goal of this clinical trial is to collect environmental, bio-humoral, and clinical data derived from patients with allergic contact dermatitis (ACD) and systemic metal allergic syndromes related to the exposure to heavy metals, nanoparticles, and emergent contaminants and from healthy subjects.

The main question it aims to answer is: are environmental, bio-humoral, and clinical data derived from patients with ACD and systemic metal allergic syndromes, related to the exposure to heavy metals, nanoparticles, and emergent contaminants, different from ones obtained by healthy subjects? Researchers will compare serum and urine concentration of heavy metals and nanoparticles, patch test to metals, within-breath analysis of oscillometry parameters, serum zonulin, and serum levels of protein oxidation products among patients with systemic allergic syndrome (1st study group), patients with ACD (2nd study group) and healthy subjects (3rd study group).

Participants will undergo:

* measurement of exposure to heavy metals and nanoparticles including nickel, cobalt, chromium, palladium, molybdenum, aluminium, and copper, through serum and urine measurement of concentration.
* Patch test to before mentioned metals.
* Within-breath analysis of oscillometry parameters.
* Measurement of serum zonulin (related to gastro-intestinal exposure).
* Measurement of serum levels of protein oxidation products (as markers of systemic oxidative stress).

Detailed description: Heavy metals \[nickel (Ni), cobalt (Co), chromium (Cr), palladium, molybdenum, aluminium, and copper\] are environmental contaminants able to impact on host cells of humans and various organisms, potentially causing serious damage. These metals can be present also in form of nanoparticles.

Nanoparticles are tiny particles between 1 and 100 nanometres in size. Nanoparticles have applications in a wide range of fields, including medicine, electronics, energy, and environmental remediation. However, the potential environmental and health risks associated with nanoparticles are also focus of global research.

The research on metal allergies in exposed subjects is challenging since the exposures are common both at the workplace and outside.

Environmental exposures are important for development of allergic contact dermatitis (ACD).

ACD is a common skin disorder caused by contact with an exogenous substance that elicits a hypersensitivity response in susceptible individuals.

Among workers exposed to such irritants and allergens at work, ACD is a common occupational health problem with a significant incidence. According to the most recent scientific studies, the overall prevalence of ACD between 1996 and 2019 is estimated at 10.5 per cent.

In some individuals, the ingestion of Ni-rich foods causes systemic skin disorders (urticaria/angioedema, erythema, eczema) and extracutaneous multi-organ symptoms (heartburn, meteorism, abdominal pain, alvo, oral aphthosis, headache, respiratory disorders, recurrent infections, fibromyalgia), expressed singularly or in variable association in some particularly sensitive subjects. This clinical picture is known as Systemic Nickel Allergy Syndrome (SNAS), which occurs in approximately 20% of ACD individuals.

Researchers will collect environmental, bio-humoral, and clinical data derived from patients with ACD and systemic metal allergic syndromes related to the exposure to heavy metals, nanoparticles, and emergent contaminants, and compare with ones obtained from healthy subjects to identify susceptibility / risk factors for these diseases.

Patients with systemic allergic syndrome (1st study group) and patients with ACD (2nd study group) will undergo the measurement of exposure to heavy metals and nanoparticles including Ni, Co, Cr, palladium, molybdenum, aluminium, and copper. Furthermore, putative effect biomarkers (patch test to metals, within-breath analysis of oscillometry parameters, and serum zonulin, related to cutaneous, respiratory, and gastro-intestinal exposure, respectively, and serum levels of protein oxidation products, as markers of systemic oxidative stress) and exposure biomarkers (serum and urinary metal concentrations) will be researched in both groups. The same investigation will be conducted on healthy subjects (3rd study group).

Eligibility criteria: Inclusion Criteria:

* adult subjects (over 18 years of age).
* Subjects suffering from allergic contact dermatitis due to metals.
* Subjects with systemic allergic syndrome due to metals.
* Adult healthy subjects.
* Subjects able to give written informed consent.

Exclusion Criteria:

* Subjects under the age of 18years.
* Pregnant/breastfeeding women.
* Subjects suffering from chronic renal failure requiring replacement treatment.
* Subjects suffering from other systemic pathologies related to exposure to metals.
* Subjects suffering from gastrointestinal diseases such as celiac disease, chronic inflammatory intestinal diseases, tumors, other skin diseases.
* Subjects unable to express written informed consent.

Primary outcomes:
measure: Serum concentration of metals
timeFrame: At enrollment.
measure: Urinary concentration of metals
timeFrame: At enrollment.
measure: Patch test
timeFrame: At enrollment.
measure: Number of subjects with altered values of respiratory system impedance
timeFrame: At enrollment.
measure: Serum concentration of zonulin
timeFrame: At enrollment.
measure: Serum concentration of protein oxidation products
timeFrame: At enrollment.
Secondary outcomes:
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Università di Bologna
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS
Study officials:
affiliation: Fondazione Policlinico Universitario A. Gemelli, IRCCS
name: Angela Rizzi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rizzi A, Lo Presti E, Chini R, Gammeri L, Inchingolo R, Lohmeyer FM, Nucera E, Gangemi S. Emerging Role of Alarmins in Food Allergy: An Update on Pathophysiological Insights, Potential Use as Disease Biomarkers, and Therapeutic Implications. J Clin Med. 2023 Apr 4;12(7):2699. doi: 10.3390/jcm12072699.
citation: Rizzi A, Chini R, Porcari S, Settanni CR, Persichetti E, Mora V, Fanali C, Leonetti A, Parrinello G, Lohmeyer FM, Inchingolo R, Mele MC, Gasbarrini A, Nucera E. Datterino Trial: A Double Blind, Randomized, Controlled, Crossover, Clinical Trial on the Use of Hydroponic Cultivated Tomato Sauce in Systemic Nickel Allergy Syndrome. J Clin Med. 2022 Sep 16;11(18):5459. doi: 10.3390/jcm11185459.
citation: Nucera E, Rizzi A, Chini R, Giangrossi S, Lohmeyer FM, Parrinello G, Musca T, Miggiano GAD, Gasbarrini A, Inchingolo R. Diet Intervention Study through Telemedicine Assistance for Systemic Nickel Allergy Syndrome Patients during the COVID-19 Pandemic. Nutrients. 2021 Aug 23;13(8):2897. doi: 10.3390/nu13082897.
citation: Rizzi A, Chini R, Inchingolo R, Carusi V, Pandolfi F, Gasbarrini A, Nucera E. Nickel allergy in lipid transfer protein sensitized patients: Prevalence and clinical features. Int J Immunopathol Pharmacol. 2020 Jan-Dec;34:2058738420974895. doi: 10.1177/2058738420974895.
citation: Rizzi A, Di Rienzo A, Buonomo A, Aruanno A, Carusi V, Ricci AG, Centrone M, Mezzacappa S, Romeo L, Schiavino D, Inchingolo R, Gasbarrini A, Nucera E. Impact of nickel oral hyposensitization on quality of life in systemic nickel allergy syndrome. Int J Immunopathol Pharmacol. 2020 Jan-Dec;34:2058738420934629. doi: 10.1177/2058738420934629.
citation: Rizzi A, Nucera E, Laterza L, Gaetani E, Valenza V, Corbo GM, Inchingolo R, Buonomo A, Schiavino D, Gasbarrini A. Irritable Bowel Syndrome and Nickel Allergy: What Is the Role of the Low Nickel Diet? J Neurogastroenterol Motil. 2017 Jan 30;23(1):101-108. doi: 10.5056/jnm16027.
citation: Campanale M, Nucera E, Ojetti V, Cesario V, Di Rienzo TA, D'Angelo G, Pecere S, Barbaro F, Gigante G, De Pasquale T, Rizzi A, Cammarota G, Schiavino D, Franceschi F, Gasbarrini A. Nickel free-diet enhances the Helicobacter pylori eradication rate: a pilot study. Dig Dis Sci. 2014 Aug;59(8):1851-5. doi: 10.1007/s10620-014-3060-3. Epub 2014 Mar 5.
citation: Patriarca G, Schiavino D, Pecora V, Lombardo C, Pollastrini E, Aruanno A, Sabato V, Colagiovanni A, Rizzi A, De Pasquale T, Roncallo C, Decinti M, Musumeci S, Gasbarrini G, Buonomo A, Nucera E. Food allergy and food intolerance: diagnosis and treatment. Intern Emerg Med. 2009 Feb;4(1):11-24. doi: 10.1007/s11739-008-0183-6. Epub 2008 Aug 16.
citation: Veneroni C, Gobbi A, Pompilio PP, Dellaca R, Fasola S, La Grutta S, Leyva A, Porszasz J, Stornelli SR, Fuso L, Valach C, Breyer-Kohansal R, Breyer MK, Hartl S, Contu C, Inchingolo R, Hodgdon K, Kaminsky DA. Reference Equations for Within-Breath Respiratory Oscillometry in White Adults. Respiration. 2024;103(9):521-534. doi: 10.1159/000539532. Epub 2024 Jun 7.