Quantitative Susceptibility Biomarker and Brain Structural Property for Cerebral Cavernous Malformation Related Epilepsy

Epilepsy Clinical Trial

— CRESS  

Official title:

Quantitative Susceptibility Mapping Biomarker, Brain Structure and Connectome Associated With Cerebral Cavernous Malformation Related Epilepsy and Outcome After Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04076449
• Other study ID #: KYSQ 2018-020-01
• Secondary ID: H0906 81801140
• Status: Recruiting
• Start date: September 3, 2019
• Est. completion date: December 31, 2026

Study information

• Verified date: September 2019
• Source: Beijing Tiantan Hospital
• Contact: Li Ma, MD, PhD
• Phone: 86-010-59978317
• Email: marygl[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Cavernous Angioma
• Cavernous Hemangioma
• Cavernous Hemangioma of Brain
• Cavernous Malformation, Cerebral
• Congenital Abnormalities
• Disease Susceptibility
• Epilepsy
• Hemangioma
• Seizures
• Seizures, Epileptic

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital, Capital Medical University	Beijing	Beijing
China	Peking University International Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
yuanli Zhao	Peking University International Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	End of study (5-year) MRI scan
Primary	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.	End of study (3-year) MRI scan after surgery
Primary	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.	End of follow-up period (5-year)
Secondary	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.	End of study (5-year) MRI scan
Secondary	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.	End of study (5-year) MRI scan