Cavernous Malformation, CerebralCRESSNCT04076449
Quantitative Susceptibility Biomarker and Brain Structural Property for Cerebral Cavernous Malformation Related Epilepsy
An observational study of Cavernous Malformation, Cerebral and Cavernous Angioma, run by yuanli Zhao at 2 sites in China.
Trial summary
Cerebral cavernous malformation (CCM)-related epilepsy (CRE) impairs the quality of life in patients with CCM. Patients could not always achieve seizure freedom after surgical resection of the lesion, suggesting an inadequate treatment and evaluation of the epileptogenic zone or network. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Cavernous Malformation, Cerebral, Cavernous Angioma, Cavernous Hemangioma
- How many people
- 200 participants
- Where
- 2 sitesChina
- Study dates
- 3 Sep 2019to 31 Dec 2026
- 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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Outpatient and inpatient referred to Beijing Tiantan Hospital and Peking University International Hospital who diagnosed with cerebral cavernous malformation.
Who may be able to join
- (1) 18 to 70 years of age
- (2) Diagnosed with a single cerebral cavernous malformation
- (3) No prior treatment of the symptomatic lesion
Who cannot join
- (1) Associated with brain lesions and/or tumors other than CCM
- (2) History of previous intracranial surgery
- (3) Prior brain irradiation
- (4) Contraindication or unwilling or unable to undergo research MRI studies
- (5) Pregnant or breastfeeding women
- (6) Persons unable or unlikely to return for follow-up visits
- (7) Dementia or other progressive neurological disease
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100079
Li Ma, MD, PhD, 86-010-59978317, marygl@hotmail.com
Yuanli Zhao, MD, 86-010-59978478, zhaoyuanli@126.com
- Recruiting
Peking University International Hospital
Beijing, Beijing Municipality, 102206
Zongze Li, MD, 86-13121226581, lizongze@pkuih.edu.cn
About this study
Official title: Quantitative Susceptibility Mapping Biomarker, Brain Structure and Connectome Associated With Cerebral Cavernous Malformation Related Epilepsy and Outcome After Surgery
Cerebral cavernous malformation (CCM)-related epilepsy (CRE) impairs the quality of life in patients with CCM. Patients could not always achieve seizure freedom after surgical resection of the lesion, suggesting an inadequate treatment and evaluation of the epileptogenic zone or network. Iron deposition in cerebral cavernous malformations has been postulated to play an important role in triggering CRE. Quantitative susceptibility mapping (QSM), as an optimal in vivo imaging technique to quantify iron deposition, is employed to analyze the iron quantity in CCM patients with epilepsy and further combined with brain structural and connectome analysis, to describe the difference between CCMs with and without epilepsy. In vivo biomarkers predicting CRE risk in CCM natural history and CRE control outcome after CCM surgical resection will be further identified to improve management strategy.
Read the detailed description
The CRESS study is a prospective observational study of imaging biomarker for cerebral cavernous malformation (CCM) related epilepsy (CRE) risk in natural history or after surgical resection. This project, funded by the National Nature Science Foundation of China, will be performed in two sites: Bejing Tiantan Hospital, Capital Medical University and Peking University International Hospital, which cover the south and north part of Beijing. Bejing Tiantan Hospital is also the China National Clinical Research Center for Neurological Diseases and the largest neurological center with high volume of patients all over the nation.
Study overview: Each participants will be followed for 5 year since enrollment. Epilepsy will be tracked with serial video EEG recordings and clinical investigations performed annually. Besides medical history of the patients, data from seizure diary and MR imaging studies (including quantitative susceptibility mapping, diffusion tensor imaging and three dimension-T1 weighted imaging), will be collected. Blood samples and tissue samples of surgical resected lesion for biomarkers studies will also be collected in all participants of the project. The data obtained in participants of CCM with or without epilepsy will be compared.
Sample size: Investigators plan to enroll 200 CCM patients in 24 months and follow up for 5 years. Based upon the preliminary results and extensive literature review, investigators predict that about 50% of participants will undergo surgical treatment, while 25% of participants remain suffering from seizure after treatment.
Study endpoints: The primary clinical endpoint of this study is a collection of a set of clinical, molecular, and MRI data in all participants.
- Conditions
- Cavernous Malformation, Cerebral, Cavernous Angioma, Cavernous Hemangioma, Cavernous Hemangioma of Brain, Seizures, Seizures, Epileptic
- Keywords
- Cerebral Cavernous Malformation, Epilepsy, Quantitative Susceptibility Mapping (QSM), Brain Connectome, Cerebral Structure
- Medical subject headings
- Hemangioma, Cavernous, Central Nervous System, Hemangioma, Cavernous, Seizures, Epilepsy
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 |
|---|---|---|
| Cerebral Cavernous Malformation with Epilepsy | Patients with cerebral cavernous malformation and associated with epilepsy will undergo MR imaging and be followed-up annually as our protocol defined. | |
| Cerebral Cavernous Malformation without Epilepsy | Patients with cerebral cavernous malformation but without epilepsy will undergo MR imaging and be followed-up annually as our protocol defined. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Perilesional mean QSM in CCM with conservative treatment
Each patient contributes five outcome measurements (at annual image of 5-year follow-up). Perilesional QSM measurements will be performed at baseline and at annual epoch of image. Perilesional mean QSM (in parts per million, ppm) in each study group will be evaluated using univariate comparison and a repeated measures analysis implemented as an unadjusted linear mixed model.
Measured: End of study (5-year) MRI scan
Perilesional mean QSM after surgical resection of CCM lesion
Each patient contributes three outcome measurements (at year 1 and 2 and 3 after surgery). Perilesional QSM measurements will be performed at annual imaging follow-up after surgery. Mean QSM (in parts per million, ppm) in patients with or without postoperative seizure will be evaluated using univariate comparison and a repeated measures analysis implemented as an unadjusted linear mixed model.
Measured: End of study (3-year) MRI scan after surgery
Ratio of seizure freedom during follow-up
Seizure freedom, defined as Engel Classification of Post-treatment Outcome Class I, will be assessed annually during follow-up period. For patients with medical treatment or conservative observation, the follow-up period begins since enrollment. For patients with surgical resection, the follow-up period begins after surgery.
Measured: End of follow-up period (5-year)
Secondary outcomes (2)
Grey matter volume in CCM with epilepsy
The presurgical grey matter volume will be calculated from three dimension T1 weighted imaging. Data of CCM with or without epilepsy will be compared and to detect the correlation between grey matter volume and seizure severity (Liverpool Seizure Severity Scale) and frequency.
Measured: End of study (5-year) MRI scan
Whole-brain connectome in CCM with epilepsy
Whole-brain connectome will be reconstructed from whole-brain diffusion tensor imaging before surgical treatment. Data of CCM with or without epilepsy will be compared.
Measured: End of study (5-year) MRI scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2019
- Study start3 Sep 2019
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cavernous Malformation, CerebralStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- yuanli Zhao
- Sponsor type
- University, hospital or other
- Collaborators
- Peking University International Hospital
- Responsible party
- Sponsor-investigator, yuanli Zhao, Beijing Tiantan Hospital
- Investigators
- Li Ma, MD, PhD, Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04076449
- Sponsor's protocol ID
- KYSQ 2018-020-01
- Other IDs
- H0906 81801140
- Acronym
- CRESS
- Status last verified
- Sep 2019
- First submitted
- 29 Aug 2019
- Last updated
- 4 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study Protocol to be published in peer-reviewed journal
Publications
Liu Y, Wen Z, Yuan J, Ma L, Wu C, Wu J, Liu Q, Zhang S, Wang S. Venous Architecture Predicts Hemorrhage Risk in Sporadic CCM With DVA. Stroke. 2025 Dec;56(12):3361-3370. doi: 10.1161/STROKEAHA.125.052339. Epub 2025 Sep 3.
PubMed 40899314Ma L, Zhang S, Li Z, Wu CX, Wang Z, Zhan L, Hao Q, Wang H, Ye X, Chen X, Liu YO, Wang S, Zhao YL. Morbidity After Symptomatic Hemorrhage of Cerebral Cavernous Malformation: A Nomogram Approach to Risk Assessment. Stroke. 2020 Oct;51(10):2997-3006. doi: 10.1161/STROKEAHA.120.029942. Epub 2020 Sep 21.
PubMed 32951540
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantitative Susceptibility Mapping Biomarker, Brain Structure and Connectome Associated With Cerebral Cavernous Malformation Related Epilepsy and Outcome After Surgery
- ClinicalTrials.gov ID
- NCT04076449
- Acronym / sponsor ID
- CRESS / KYSQ 2018-020-01
- Conditions
- Cavernous Malformation, Cerebral, Cavernous Angioma, Cavernous Hemangioma, Cavernous Hemangioma of Brain, Seizures, Seizures, Epileptic
- Keywords
- Cerebral Cavernous Malformation, Epilepsy, Quantitative Susceptibility Mapping (QSM), Brain Connectome, Cerebral Structure
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- yuanli ZhaoUniversity, hospital or other
- Collaborators
- Peking University International Hospital
- Study start
- 3 Sep 2019 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 3 Sep 2019 (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.
Cerebral cavernous malformation (CCM)-related epilepsy (CRE) impairs the quality of life in patients with CCM. Patients could not always achieve seizure freedom after surgical resection of the lesion, suggesting an inadequate treatment and evaluation of the epileptogenic zone or network. Iron deposition in cerebral cavernous malformations has been postulated to play an important role in triggering CRE. Quantitative susceptibility mapping (QSM), as an optimal in vivo imaging technique to quantify iron deposition, is employed to analyze the iron quantity in CCM patients with epilepsy and further combined with brain structural and connectome analysis, to describe the difference between CCMs with and without epilepsy. In vivo biomarkers predicting CRE risk in CCM natural history and CRE control outcome after CCM surgical resection will be further identified to improve management strategy.
Detailed description
The CRESS study is a prospective observational study of imaging biomarker for cerebral cavernous malformation (CCM) related epilepsy (CRE) risk in natural history or after surgical resection. This project, funded by the National Nature Science Foundation of China, will be performed in two sites: Bejing Tiantan Hospital, Capital Medical University and Peking University International Hospital, which cover the south and north part of Beijing. Bejing Tiantan Hospital is also the China National Clinical Research Center for Neurological Diseases and the largest neurological center with high volume of patients all over the nation.
Study overview: Each participants will be followed for 5 year since enrollment. Epilepsy will be tracked with serial video EEG recordings and clinical investigations performed annually. Besides medical history of the patients, data from seizure diary and MR imaging studies (including quantitative susceptibility mapping, diffusion tensor imaging and three dimension-T1 weighted imaging), will be collected. Blood samples and tissue samples of surgical resected lesion for biomarkers studies will also be collected in all participants of the project. The data obtained in participants of CCM with or without epilepsy will be compared.
Sample size: Investigators plan to enroll 200 CCM patients in 24 months and follow up for 5 years. Based upon the preliminary results and extensive literature review, investigators predict that about 50% of participants will undergo surgical treatment, while 25% of participants remain suffering from seizure after treatment.
Study endpoints: The primary clinical endpoint of this study is a collection of a set of clinical, molecular, and MRI data in all participants.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cerebral Cavernous Malformation with Epilepsy | – | –Patients with cerebral cavernous malformation and associated with epilepsy will undergo MR imaging and be followed-up annually as our protocol defined. |
| Cerebral Cavernous Malformation without Epilepsy | – | –Patients with cerebral cavernous malformation but without epilepsy will undergo MR imaging and be followed-up annually as our protocol defined. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Outpatient and inpatient referred to Beijing Tiantan Hospital and Peking University International Hospital who diagnosed with cerebral cavernous malformation.
Key inclusion criteria (3 listed)
- (1) 18 to 70 years of age
- (2) Diagnosed with a single cerebral cavernous malformation
- (3) No prior treatment of the symptomatic lesion
Key exclusion criteria (7 listed)
- (1) Associated with brain lesions and/or tumors other than CCM
- (2) History of previous intracranial surgery
- (3) Prior brain irradiation
- (4) Contraindication or unwilling or unable to undergo research MRI studies
- (5) Pregnant or breastfeeding women
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
Perilesional mean QSM in CCM with conservative treatment
Time frame: End of study (5-year) MRI scan
Each patient contributes five outcome measurements (at annual image of 5-year follow-up). Perilesional QSM measurements will be performed at baseline and at annual epoch of image. Perilesional mean QSM (in parts per million, ppm) in each study group will be evaluated using univariate comparison and a repeated measures analysis implemented as an unadjusted linear mixed model.
Perilesional mean QSM after surgical resection of CCM lesion
Time frame: End of study (3-year) MRI scan after surgery
Each patient contributes three outcome measurements (at year 1 and 2 and 3 after surgery). Perilesional QSM measurements will be performed at annual imaging follow-up after surgery. Mean QSM (in parts per million, ppm) in patients with or without postoperative seizure will be evaluated using univariate comparison and a repeated measures analysis implemented as an unadjusted linear mixed model.
Ratio of seizure freedom during follow-up
Time frame: End of follow-up period (5-year)
Seizure freedom, defined as Engel Classification of Post-treatment Outcome Class I, will be assessed annually during follow-up period. For patients with medical treatment or conservative observation, the follow-up period begins since enrollment. For patients with surgical resection, the follow-up period begins after surgery.
2 secondary outcomes
Grey matter volume in CCM with epilepsy
Time frame: End of study (5-year) MRI scan
Whole-brain connectome in CCM with epilepsy
Time frame: End of study (5-year) MRI scan
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 4 Sep 2019.
- Derived from this study: PubMed 40899314Liu Y, Wen Z, Yuan J, Ma L, Wu C, Wu J, Liu Q, Zhang S, Wang S. Venous Architecture Predicts Hemorrhage Risk in Sporadic CCM With DVA. Stroke. 2025 Dec;56(12):3361-3370. doi: 10.1161/STROKEAHA.125.052339. Epub 2025 Sep 3.
- Derived from this study: PubMed 32951540Ma L, Zhang S, Li Z, Wu CX, Wang Z, Zhan L, Hao Q, Wang H, Ye X, Chen X, Liu YO, Wang S, Zhao YL. Morbidity After Symptomatic Hemorrhage of Cerebral Cavernous Malformation: A Nomogram Approach to Risk Assessment. Stroke. 2020 Oct;51(10):2997-3006. doi: 10.1161/STROKEAHA.120.029942. Epub 2020 Sep 21.
- Individual participant dataSharing planned: Yes. Study Protocol to be published in peer-reviewed journal
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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.
Li Ma, MD, PhD principal investigator
Beijing Tiantan Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cavernous Malformation, Cerebral and Cavernous Angioma, run by yuanli Zhao at 2 sites in China.
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 3 inclusion and 7 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 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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 Li Ma, MD, PhD (86-010-59978317, marygl@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Perilesional mean QSM in CCM with conservative treatment (time frame: End of study (5-year) MRI scan). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04076449, which also lists 2 linked publications.
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 4 Sep 2019.