COL4A1\2NCT07374913
COL4A1COL4A2: Study of Pathological Conditions Involving Multiple Organs Caused by Mutations in the COL4A1 and COL4A2 Genes
A study testing Ophtalmological and cardiological screening in people with COL4A1\2 and COL4A1-Related Brain Small Vessel Disease With Haemorrhage, run by Meyer Children's Hospital IRCCS at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- COL4A1\2, COL4A1-Related Brain Small Vessel Disease With Haemorrhage
- What is being tested?
- Ophtalmological and cardiological screening
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteItaly
- Study dates
- 1 May 2021to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Refusal or inability to provide informed consent.
- Individuals who do not meet the inclusion criteria above.
- Any condition that, in the opinion of the investigators, would preclude participation in study procedures or reliable data collection.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Meyer Children's Hospital IRCSS
Florence, FI, 50139
Simona Balestrini, 3713764672, simona.balestrini@meyer.it
About this study
Official title: Study of the Familial Phenotype Associated With Mutations in the COL4A1 and COL4A2 Genes
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.
Read more
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.
Read the detailed description
This is an observational, prospective cohort study designed to characterize the clinical spectrum and underlying biological mechanisms associated with pathogenic or likely pathogenic variants in the COL4A1 and COL4A2 genes. These genes encode type IV collagen, a key structural component of basement membranes, and their alteration is associated with a rare autosomal dominant small-vessel disease with variable multi-organ involvement.
Individuals with a confirmed COL4A1/COL4A2 mutation identified through clinical genetic testing will be invited to participate together with their first-degree family members. Adult relatives who are confirmed carriers or are suspected carriers of the same mutation will be included in the diagnostic component of the study. Adult non-carrier relatives will serve as controls for selected laboratory analyses.
Participants will complete a structured questionnaire collecting standardized information on neurological, ophthalmological, cardiovascular, renal, muscular, and other systemic manifestations. Carrier or suspected carrier relatives will be offered non-invasive diagnostic screening, including ophthalmological assessments (anterior segment photography and optical coherence tomography) and cardiological evaluations (resting electrocardiogram, ambulatory ECG monitoring, and echocardiography), performed within routine clinical care settings.
A blood sample will be collected from affected individuals and adult non-carrier relatives. Plasma will be stored and analyzed to assess the activity of matrix metalloproteinases MMP2 and MMP9 using established laboratory techniques. These analyses aim to explore molecular pathways potentially involved in vascular and tissue damage associated with COL4A1/COL4A2 variants.
The study does not include a scheduled follow-up; data are collected at a single time point per participant. Results will be analyzed using descriptive and exploratory statistical methods to evaluate the prevalence and pattern of multi-organ involvement and to explore associations between genetic variants, clinical features, and laboratory findings.
The knowledge gained from this study is intended to support improved clinical characterization of COL4A1/COL4A2-related disease, inform the development of structured multi-organ screening strategies, and provide a foundation for future therapeutic research
- Being tested
- Ophtalmological and cardiological screening
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ophtalmological and cardiological screeningDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Ophtalmological and cardiological screening |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence and pattern of multi-organ involvement
Measured: Single time point at study enrollment (baseline assessment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2026
- Study start1 May 2021
- Primary completionNov 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COL4A1\2Studies of the same condition, open and under way.
- More trials run by Meyer Children's Hospital IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Meyer Children's Hospital IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Simona Balestrini, Meyer Children's Hospital IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07374913
- Sponsor's protocol ID
- COL4A1COL4A2
- Status last verified
- Jan 2026
- First submitted
- 21 Jan 2026
- Last updated
- 30 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Familial Phenotype Associated With Mutations in the COL4A1 and COL4A2 Genes
- ClinicalTrials.gov ID
- NCT07374913
- Acronym / sponsor ID
- COL4A1COL4A2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Meyer Children's Hospital IRCCSUniversity, hospital or other
- Study start
- 1 May 2021 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 29 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an observational, prospective cohort study designed to characterize the clinical spectrum and underlying biological mechanisms associated with pathogenic or likely pathogenic variants in the COL4A1 and COL4A2 genes. These genes encode type IV collagen, a key structural component of basement membranes, and their alteration is associated with a rare autosomal dominant small-vessel disease with variable multi-organ involvement.
Individuals with a confirmed COL4A1/COL4A2 mutation identified through clinical genetic testing will be invited to participate together with their first-degree family members. Adult relatives who are confirmed carriers or are suspected carriers of the same mutation will be included in the diagnostic component of the study. Adult non-carrier relatives will serve as controls for selected laboratory analyses.
Participants will complete a structured questionnaire collecting standardized information on neurological, ophthalmological, cardiovascular, renal, muscular, and other systemic manifestations. Carrier or suspected carrier relatives will be offered non-invasive diagnostic screening, including ophthalmological assessments (anterior segment photography and optical coherence tomography) and cardiological evaluations (resting electrocardiogram, ambulatory ECG monitoring, and echocardiography), performed within routine clinical care settings.
A blood sample will be collected from affected individuals and adult non-carrier relatives. Plasma will be stored and analyzed to assess the activity of matrix metalloproteinases MMP2 and MMP9 using established laboratory techniques. These analyses aim to explore molecular pathways potentially involved in vascular and tissue damage associated with COL4A1/COL4A2 variants.
The study does not include a scheduled follow-up; data are collected at a single time point per participant. Results will be analyzed using descriptive and exploratory statistical methods to evaluate the prevalence and pattern of multi-organ involvement and to explore associations between genetic variants, clinical features, and laboratory findings.
The knowledge gained from this study is intended to support improved clinical characterization of COL4A1/COL4A2-related disease, inform the development of structured multi-organ screening strategies, and provide a foundation for future therapeutic research
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| COL4A1/2 variant carriers | Experimental | Diagnostic Test: Ophtalmological and cardiological screeningThis 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- Refusal or inability to provide informed consent.
- Individuals who do not meet the inclusion criteria above.
- Any condition that, in the opinion of the investigators, would preclude participation in study procedures or reliable data collection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ophtalmological and cardiological screeningParticipants 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. | Diagnostic test | COL4A1/2 variant carriers |
Primary outcome
Prevalence and pattern of multi-organ involvement
Time frame: Single time point at study enrollment (baseline assessment)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ophtalmological and cardiological screening in people with COL4A1\2 and COL4A1-Related Brain Small Vessel Disease With Haemorrhage, run by Meyer Children's Hospital IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact SIMONA Balestrini, Md, PhD (+390555662719, simona.balestrini@meyer.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence and pattern of multi-organ involvement (time frame: Single time point at study enrollment (baseline assessment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2026.