COL4A1COL4A2: Study of Pathological Conditions Involving Multiple Organs Caused by Mutations in the COL4A1 and COL4A2 Genes

NCT07374913 | Recruiting

• 1 other identifier: COL4A1COL4A2
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This observational and diagnostic study aims to better understand the clinical features and biological mechanisms associated with mutations in the COL4A1 and COL4A2 genes, which are known to cause a rare inherited small-vessel disease affecting the brain and other organs. These mutations can lead to a wide range of symptoms involving the brain, eyes, heart, blood vessels, kidneys, and muscles, and affected individuals within the same family may show very different clinical manifestations. The study will systematically collect clinical and diagnostic information from individuals with confirmed COL4A1/COL4A2 mutations and their first-degree family members, including both affected and unaffected relatives. Family members who carry, or may carry, the mutation will be offered non-invasive eye and heart examinations to detect early or previously unrecognized organ involvement. In addition, blood samples will be analyzed to study the activity of specific enzymes called matrix metalloproteinases (MMP2 and MMP9), which are thought to play a role in blood vessel damage in this condition. By linking genetic findings, clinical features, and laboratory data, the study seeks to clarify how these mutations cause disease and to identify early signs of organ involvement. The overall goal of the study is to improve early diagnosis, guide the development of routine multi-organ screening strategies for affected individuals and families, and support future research toward targeted treatments.

Conditions

COL4A1\2; COL4A1-Related Brain Small Vessel Disease With Haemorrhage

Outcome Measures

Primary Outcomes (1)

• Prevalence and pattern of multi-organ involvement

  Single time point at study enrollment (baseline assessment)

Study Arms (1)

COL4A1/2 variant carriers

EXPERIMENTAL

This is a single-arm observational study with defined participant subgroups. No experimental interventions are administered. Participants include individuals with pathogenic or likely pathogenic COL4A1 or COL4A2 variants and their first-degree family members. All participants undergo observational data collection through a structured clinical questionnaire. Adult family members who are confirmed or suspected carriers of the mutation are additionally offered non-invasive diagnostic assessments, including ophthalmological examinations (anterior segment photography and optical coherence tomography) and cardiological evaluations (resting ECG, ambulatory ECG, and echocardiography), performed as part of routine clinical care. A blood sample is collected from affected individuals and adult non-carrier relatives for exploratory laboratory analyses of matrix metalloproteinase (MMP2/MMP9) activity. Non-carrier relatives serve as a biological control group for these analyses.

Diagnostic Test: Ophtalmological and cardiological screening

Interventions

Ophtalmological and cardiological screening DIAGNOSTIC_TEST

Participants who are confirmed or suspected carriers of a COL4A1 or COL4A2 pathogenic variant are offered non-invasive diagnostic ophthalmological and cardiological screening to assess potential organ involvement associated with the genetic condition. The ophthalmological screening includes anterior segment photography of both eyes and optical coherence tomography (OCT) to evaluate retinal structure, macular thickness, and retinal nerve fiber layer. The cardiological screening includes a resting electrocardiogram (ECG), ambulatory ECG monitoring, and transthoracic echocardiography to assess heart rhythm, conduction, and cardiac structure and function. These procedures are performed within routine clinical care settings and are used solely for observational and diagnostic purposes; no therapeutic intervention is administered as part of the study.

COL4A1/2 variant carriers

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals (pediatric or adult) with a pathogenic or likely pathogenic mutation in the COL4A1 or COL4A2 genes and a clinical phenotype consistent with small vessel disease.
• Adult first-degree family members (parents, siblings, or children) who are confirmed carriers or suspected carriers of the same COL4A1/COL4A2 mutation.
• Adult first-degree family members who are non-carriers of the pathogenic mutation and who agree to provide a blood sample to be used as controls for laboratory analyses.
• Ability to provide written informed consent; for minors, consent provided by a parent or legal guardian.

You may not qualify if:

• Refusal or inability to provide informed consent.
• Any condition that, in the opinion of the investigators, would preclude participation in study procedures or reliable data collection.

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead

Study Sites (1)

Meyer Children's Hospital IRCSS

Florence, FI, 50139, Italy

RECRUITING

Central Study Contacts

SIMONA Balestrini, Md, PhD

CONTACT

+390555662719; simona.balestrini@meyer.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: January 21, 2026
• First Posted: January 29, 2026
• Study Start: May 1, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)