Genetics and Environment iNtersection In the ALS-FTD Spectrum: an Italian Twins Cohort studY With a Multi-Omics Approach

NCT06595212 | Recruiting

• 1 other identifier: PNRR-MAD-2022-12375798
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this study is to learn from discordant twins affected by Amyotrophic Lateral Sclerosis and/or Frontotemporal Dementia the contribution of genetic background versus environmental exposure. The main questions it aims to answer is:

• How far does the genetic background explain the onset of ALS/FTD in discordant twins?
• Which environmental factors and events occurring in post-fetal life influence the onset or progression of this neurodegenerative condition? Participants with ALS and/or FTD with a monozygotic or dizygotic twin willing to contribute to this research will be followed up for two years by specialized Motor Neuron Disorders centers in Italy, donating biological specimen for -omic sciences analysis, and checking out if prodromal signs/symptoms of these two conditions will develop during time.

Conditions

ALS; FTD

Keywords

ALS; FTD; twin; cohort

Outcome Measures

Primary Outcomes (1)

• Environmental/genetic risk/protective factors involved in driving discordance in monozygotic (MZ) twins

  Using a multi-omic approach, the investigators will establish a longitudinal cohort of Italian twins affected by ALS/FTD, collecting various samples to compare affected and unaffected twins across multiple biological and phenotypic variables. The aim is to uncover the factors underlying discordance in monozygotic twins, identifying what protects the unaffected twins and what predisposes the affected ones.

  24 months

Study Arms (2)

affected twins

Other: multiomic profile to assess genetic and environmental risk factiors

unaffected twins

Other: multiomic profile to assess genetic and environmental risk factiors

Interventions

multiomic profile to assess genetic and environmental risk factiors OTHER

Genomic, epigenetic, proteomic, microbiome, immunology, biomarker, metabolite, pesticide, metal, and metalloid investigations will be conducted. The twins will be followed longitudinally from a clinical perspective, with biological sample collections to assess discordance and identify early disease signatures in unaffected individuals.

affected twins; unaffected twins

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population include all Italian participants with ALS and/or FTD who have a mozygotic or dizygotic twin with (concordant) or without (discordant) the same condition willing to participate in the study. Once the consent is obtained, the twins will be followed up for 24 months in three possible Italian recruiting centres (Modena, Turin, Palermo).

You may qualify if:

• Age \>18 yrs
• Presence of MZ or DZ twins in the family both willing to participate in the study and able to provide informed consent
• At least one twin is affected by ALS as defined by Gold Coast Criteria (Shefner et al., 2020) and/or by FTD as defined by Strong and colleagues (Strong et al., 2017)
• Subjects able and willing to comply with study procedures as per protocol
• Subjects able to understand, and capable of providing informed consent at screening visit before any protocol-specific procedures

You may not qualify if:

• Unwillingness to perform assessments as stated in the protocol at least during baseline visit for both twins
• Unwillingness to donate biological samples collected at periphery (lumbar puncture excluded) for both twins
• Women who are pregnant or breastfeeding

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Modena: lead
• A.O.U. Città della Salute e della Scienza - Molinette Hospital: collaborator
• Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo: collaborator
• University of Modena and Reggio Emilia: collaborator
• Azienda Ospedaliero-Universitaria Careggi: collaborator

Study Sites (3)

Azienda Ospedaliero-Universitaria di Modena

Modena, Italy, 41125, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Policlinico P. Giaccone di Palermo

Palermo, Italy, 90127, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino

Torino, Italy, 10126, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood, CSF (optional), skin, hair, saliva and stool collection

Central Study Contacts

Jessica Mandrioli, MD, Prof

CONTACT

0593961640; jessica.mandrioli@unimore.it

Cecilia Simonini, BSc

CONTACT

0593961640; ceciliasimonini24@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: September 11, 2024
• First Posted: September 19, 2024
• Study Start: January 29, 2024
• Primary Completion: January 29, 2026
• Study Completion: January 30, 2026
• Last Updated: February 4, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

IT (3)