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

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ClinicalTrials.gov Identifier: NCT04076449
Recruitment Status : Recruiting
First Posted : September 2, 2019
Last Update Posted : September 4, 2019
Sponsor:
Collaborator:
Peking University International Hospital
Information provided by (Responsible Party):
yuanli Zhao, Beijing Tiantan Hospital

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.

Condition or disease
Cavernous Malformation, Cerebral Cavernous Angioma Cavernous Hemangioma Cavernous Hemangioma of Brain Seizures Seizures, Epileptic Epilepsy

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.


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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Quantitative Susceptibility Mapping Biomarker, Brain Structure and Connectome Associated With Cerebral Cavernous Malformation Related Epilepsy and Outcome After Surgery
Actual Study Start Date : September 3, 2019
Estimated Primary Completion Date : December 31, 2026
Estimated Study Completion Date : December 31, 2026


Group/Cohort
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.



Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. Grey matter volume in CCM with epilepsy [ Time Frame: End of study (5-year) MRI scan ]
    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.

  2. Whole-brain connectome in CCM with epilepsy [ Time Frame: End of study (5-year) MRI scan ]
    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.


Biospecimen Retention:   Samples With DNA
Surgical resected lesion and 20 ml blood sample before surgery


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04076449


Contacts
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Contact: Li Ma, MD, PhD 86-010-59978317 marygl@hotmail.com
Contact: Yuanli Zhao, MD 86-010-59978478 zhaoyuanli@126.com

Locations
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China, Beijing
Beijing Tiantan Hospital, Capital Medical University Recruiting
Beijing, Beijing, China, 100079
Contact: Li Ma, MD, PhD    86-010-59978317    marygl@hotmail.com   
Contact: Yuanli Zhao, MD    86-010-59978478    zhaoyuanli@126.com   
Sub-Investigator: Chunxue Wu, MD         
Peking University International Hospital Recruiting
Beijing, Beijing, China, 102206
Contact: Zongze Li, MD    86-13121226581    lizongze@pkuih.edu.cn   
Sponsors and Collaborators
yuanli Zhao
Peking University International Hospital
Investigators
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Principal Investigator: Li Ma, MD, PhD Beijing Tiantan Hospital

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Responsible Party: yuanli Zhao, Professor, Department of Neurosurgery, Beijing Tiantan Hospital
ClinicalTrials.gov Identifier: NCT04076449     History of Changes
Other Study ID Numbers: KYSQ 2018-020-01
H0906 81801140 ( Other Grant/Funding Number: National Nature Science Foundation )
First Posted: September 2, 2019    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Study Protocol to be published in peer-reviewed journal
Supporting Materials: Study Protocol
Time Frame: Since the publication of study protocol
Access Criteria: Available from the principle investigator upon reasonable request

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by yuanli Zhao, Beijing Tiantan Hospital:
Cerebral Cavernous Malformation
Epilepsy
Quantitative Susceptibility Mapping (QSM)
Brain Connectome
Cerebral Structure
Additional relevant MeSH terms:
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Epilepsy
Hemangioma
Hemangioma, Cavernous, Central Nervous System
Hemangioma, Cavernous
Seizures
Congenital Abnormalities
Disease Susceptibility
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Disease Attributes
Pathologic Processes
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Central Nervous System Vascular Malformations
Nervous System Malformations
Vascular Malformations
Cardiovascular Abnormalities
Cardiovascular Diseases
Hemostatic Disorders
Vascular Diseases
Hemorrhagic Disorders
Hematologic Diseases