Clinical trial NCT04076449: Quantitative Susceptibility Biomarker and Brain Structural Property for Cerebral Cavernous Malformation Related Epilepsy
Official title: Quantitative Susceptibility Mapping Biomarker, Brain Structure and Connectome Associated With Cerebral Cavernous Malformation Related Epilepsy and Outcome After Surgery
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cavernous Malformation, Cerebral
Cavernous Angioma
Cavernous Hemangioma
Cavernous Hemangioma of Brain
Seizures
Seizures, Epileptic
Epilepsy
Keywords: Cerebral Cavernous Malformation
Epilepsy
Quantitative Susceptibility Mapping (QSM)
Brain Connectome
Cerebral Structure
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Peking University International Hospital
First posted: 2019-09-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Outpatient and inpatient referred to Beijing Tiantan Hospital and Peking University International Hospital who diagnosed with cerebral cavernous malformation.

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* (1) 18 to 70 years of age
* (2) Diagnosed with a single cerebral cavernous malformation
* (3) No prior treatment of the symptomatic lesion

Exclusion Criteria:

* (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

Primary outcomes:
measure: Perilesional mean QSM in CCM with conservative treatment
timeFrame: End of study (5-year) MRI scan
measure: Perilesional mean QSM after surgical resection of CCM lesion
timeFrame: End of study (3-year) MRI scan after surgery
measure: Ratio of seizure freedom during follow-up
timeFrame: End of follow-up period (5-year)
Secondary outcomes:
measure: Grey matter volume in CCM with epilepsy
timeFrame: End of study (5-year) MRI scan
measure: Whole-brain connectome in CCM with epilepsy
timeFrame: End of study (5-year) MRI scan
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University International Hospital
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Li Ma, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ma 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.