Brain Arteriovenous Malformations (AVMs)SHAMNCT07676721
Shh Signaling in Brain AVMs: Novel Player & Therapeutic Target
An observational study of Brain Arteriovenous Malformations (AVMs), run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
The present study, entitled "SHAM Study," is a prospective observational translational study aimed at investigating the molecular mechanisms underlying brain arteriovenous malformations (AVMs). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Arteriovenous Malformations (AVMs)
- How many people
- 45 participants
- Where
- 1 siteItaly
- Study dates
- 1 Aug 2026to 1 Aug 2029
- How long will I take part?
- 1 Day
- Phase
- Observational
- 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 18 years and older
- All sexes
- Adult, Older adult
Study population: Adults ≥18 years undergoing neurosurgical intervention with resection of AVM or non-pathological cortical tissue (controls).
Who may be able to join
- Adult patients aged 18 years or older undergoing neurosurgical resection who provide written informed consent for research use of residual tissue.
Who cannot join
- Tissue with extensive necrosis or contamination, lack of valid consent, or known infectious agents that preclude safe handling.
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
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, Rome, 00168
Roberto Pola, Professor, MD, 0630151 ext. +39, roberto.pola@policlinicogemelli.it
About this study
Official title: Sonic Hedgehog Signaling: Novel Player and Potential Therapeutic Target in Brain Arteriovenous Malformations
The present study, entitled "SHAM Study," is a prospective observational translational study aimed at investigating the molecular mechanisms underlying brain arteriovenous malformations (AVMs). In particular, the study seeks to explore the role of the Sonic Hedgehog (Shh) signaling pathway, which has recently been hypothesized as a potential key player in pathological angiogenesis and in the maintenance of the malformative nidus.
The study will be conducted through the analysis of brain tissues obtained exclusively as residual material from neurosurgical procedures performed for clinical indications. Under no circumstances will additional procedures be carried out or modifications made to the patients' therapeutic pathway for research purposes. Samples will include tissues from adult patients undergoing AVM resection and, as controls, non-pathological brain tissues derived from surgeries performed for other indications, such as drug-resistant epilepsy.
Read more
The methodological approach involves the isolation of endothelial cells from collected samples and their characterization using multi-omics techniques, including transcriptomic analysis, microRNA profiling, and quantitative proteomics. The resulting data will be integrated through advanced bioinformatics analyses in order to identify specific molecular patterns, altered pathways, and potential biomarkers. Particular attention will be given to the evaluation of Shh pathway activation and its interactions with other signaling systems involved in AVM pathogenesis.
The collected biological material may also be used, subject to specific informed consent, for preclinical studies conducted on animal models, with the aim of further investigating the identified pathogenetic mechanisms and assessing their functional relevance. Such activities will be carried out in compliance with current regulations on animal experimentation and subject to approval by the relevant authorities.
The primary objective of the study is to identify significant differences in gene expression between endothelial cells derived from AVMs and control brain tissue. Secondary objectives include the identification of integrated molecular profiles (RNA, microRNA, and proteins), the correlation of these profiles with patients' clinical and radiological characteristics, and the identification of potential therapeutic targets.
The study is designed so as not to entail additional risks for participants, as it is based exclusively on the use of biological material that would otherwise be discarded. All subjects will be enrolled only after providing written informed consent. Data will be processed in pseudonymized form in compliance with current regulations on personal data protection.
The total expected duration is 36 months, and the study is part of a targeted research project aimed at generating new knowledge with potential translational impact, laying the groundwork for the future development of targeted therapeutic strategies.
Study duration and number of patients:
The overall duration of the study will be 36 months. Enrollment will begin immediately after ethical approval and will be completed by month 24.
A total of 30-45 adult patients are expected to be enrolled, including 20-30 undergoing resection of brain arteriovenous malformations and 10-15 patients undergoing neurosurgical procedures for drug-resistant epilepsy, from whom non-pathological cortical tissue will be obtained.
- Conditions
- Brain Arteriovenous Malformations (AVMs)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| AVM group (cases) | Adult patients undergoing neurosurgical resection of brain arteriovenous malformations for clinically indicated reasons. Residual AVM tissue obtained during surgery will be used for molecular analyses. | |
| Control group | Adult patients undergoing neurosurgical procedures for drug-resistant epilepsy or other clinical indications, from whom non-pathological brain tissue is resected as part of standard care. Residual tissue will be used as control. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differential endothelial gene expression between AVM and control tissues.
Endothelial differential gene expression measured as log2 fold change and adjusted p value from bulk RNA seq.
Measured: Up to 34 months
Secondary outcomes (1)
MicroRNA and proteomic profiles, pathway activity scores, histological markers, and clinical correlations.
MicroRNA abundance (normalized counts); protein abundance (LFQ intensity); pathway activity scores (Shh, Notch, VEGF, TGF β/ALK1, MAPK); histological metrics (percent positive area; mean staining intensity for Shh, Gli1, CD31, α SMA).
Measured: Up to 34 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2026
- Study start1 Aug 2026 (estimated)
- Primary completion1 Jun 2029 (estimated)
- Study completion1 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Arteriovenous Malformations (AVMs)Studies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 45 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pola Roberto, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07676721
- Sponsor's protocol ID
- 27587
- Acronym
- SHAM
- Status last verified
- Jun 2026
- First submitted
- 24 Jun 2026
- Last updated
- 30 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sonic Hedgehog Signaling: Novel Player and Potential Therapeutic Target in Brain Arteriovenous Malformations
- ClinicalTrials.gov ID
- NCT07676721
- Acronym / sponsor ID
- SHAM / 27587
- Conditions
- Brain Arteriovenous Malformations (AVMs)
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 1 Aug 2026 (estimated)
- Primary completion
- 1 Jun 2029 (estimated)
- Study completion
- 1 Aug 2029 (estimated)
- First posted
- 30 Jun 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.
The present study, entitled "SHAM Study," is a prospective observational translational study aimed at investigating the molecular mechanisms underlying brain arteriovenous malformations (AVMs). In particular, the study seeks to explore the role of the Sonic Hedgehog (Shh) signaling pathway, which has recently been hypothesized as a potential key player in pathological angiogenesis and in the maintenance of the malformative nidus.
The study will be conducted through the analysis of brain tissues obtained exclusively as residual material from neurosurgical procedures performed for clinical indications. Under no circumstances will additional procedures be carried out or modifications made to the patients' therapeutic pathway for research purposes. Samples will include tissues from adult patients undergoing AVM resection and, as controls, non-pathological brain tissues derived from surgeries performed for other indications, such as drug-resistant epilepsy.
The methodological approach involves the isolation of endothelial cells from collected samples and their characterization using multi-omics techniques, including transcriptomic analysis, microRNA profiling, and quantitative proteomics. The resulting data will be integrated through advanced bioinformatics analyses in order to identify specific molecular patterns, altered pathways, and potential biomarkers. Particular attention will be given to the evaluation of Shh pathway activation and its interactions with other signaling systems involved in AVM pathogenesis.
The collected biological material may also be used, subject to specific informed consent, for preclinical studies conducted on animal models, with the aim of further investigating the identified pathogenetic mechanisms and assessing their functional relevance. Such activities will be carried out in compliance with current regulations on animal experimentation and subject to approval by the relevant authorities.
The primary objective of the study is to identify significant differences in gene expression between endothelial cells derived from AVMs and control brain tissue. Secondary objectives include the identification of integrated molecular profiles (RNA, microRNA, and proteins), the correlation of these profiles with patients' clinical and radiological characteristics, and the identification of potential therapeutic targets.
The study is designed so as not to entail additional risks for participants, as it is based exclusively on the use of biological material that would otherwise be discarded. All subjects will be enrolled only after providing written informed consent. Data will be processed in pseudonymized form in compliance with current regulations on personal data protection.
The total expected duration is 36 months, and the study is part of a targeted research project aimed at generating new knowledge with potential translational impact, laying the groundwork for the future development of targeted therapeutic strategies.
Study duration and number of patients:
The overall duration of the study will be 36 months. Enrollment will begin immediately after ethical approval and will be completed by month 24.
A total of 30-45 adult patients are expected to be enrolled, including 20-30 undergoing resection of brain arteriovenous malformations and 10-15 patients undergoing neurosurgical procedures for drug-resistant epilepsy, from whom non-pathological cortical tissue will be obtained.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Day
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AVM group (cases) | – | –Adult patients undergoing neurosurgical resection of brain arteriovenous malformations for clinically indicated reasons. Residual AVM tissue obtained during surgery will be used for molecular analyses. |
| Control group | – | –Adult patients undergoing neurosurgical procedures for drug-resistant epilepsy or other clinical indications, from whom non-pathological brain tissue is resected as part of standard care. Residual tissue will be used as control. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Adults ≥18 years undergoing neurosurgical intervention with resection of AVM or non-pathological cortical tissue (controls).
Key inclusion criteria (1 listed)
- Adult patients aged 18 years or older undergoing neurosurgical resection who provide written informed consent for research use of residual tissue.
Key exclusion criteria (1 listed)
- Tissue with extensive necrosis or contamination, lack of valid consent, or known infectious agents that preclude safe handling.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Differential endothelial gene expression between AVM and control tissues.
Time frame: Up to 34 months
Endothelial differential gene expression measured as log2 fold change and adjusted p value from bulk RNA seq.
1 secondary outcome
MicroRNA and proteomic profiles, pathway activity scores, histological markers, and clinical correlations.
Time frame: Up to 34 months
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 Jun 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Brain Arteriovenous Malformations (AVMs)
Recruiting
Treatment of Brain AVMs (TOBAS) Study
Unruptured Brain Arteriovenous Malformation, Ruptured Brain Arteriovenous Malformation
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.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Arteriovenous Malformations (AVMs), run by Fondazione Policlinico Universitario Agostino Gemelli 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 1 inclusion and 1 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: opening soon, as of the sponsor's last update on 30 Jun 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differential endothelial gene expression between AVM and control tissues. (time frame: Up to 34 months). 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 Jun 2026.