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

NCT04076449 | Recruiting DMC

• 2 other identifiers: KYSQ 2018-020-01H0906 81801140
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (2)

• Grey matter volume in CCM with epilepsy

  End of study (5-year) MRI scan

• Whole-brain connectome in CCM with epilepsy

  End of study (5-year) MRI scan

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• (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

Sponsors & Collaborators

• yuanli Zhao: lead
• Peking University International Hospital: collaborator

Study Sites (2)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100079, China

RECRUITING

Peking University International Hospital

Beijing, Beijing Municipality, 102206, China

RECRUITING

Related Publications (2)

• 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.

  PMID: 40899314 DERIVED

• 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.

  PMID: 32951540 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Surgical resected lesion and 20 ml blood sample before surgery

MeSH Terms

Conditions

Hemangioma, Cavernous, Central Nervous System; Hemangioma, Cavernous; Seizures; Epilepsy

Condition Hierarchy (Ancestors)

Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Cavernous Sinus Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Central Nervous System Vascular Malformations; Nervous System Malformations; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Hemostatic Disorders; Vascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Li Ma, MD, PhD

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Ma, MD, PhD

CONTACT

86-010-59978317; marygl@hotmail.com

Yuanli Zhao, MD

CONTACT

86-010-59978478; zhaoyuanli@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Neurosurgery

Study Record Dates

• First Submitted: August 29, 2019
• First Posted: September 3, 2019
• Study Start: September 3, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 4, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Since the publication of study protocol
• Access Criteria: Available from the principle investigator upon reasonable request

Locations

CN (2)