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

September 3, 2019 updated by: yuanli Zhao

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.

Study Overview

Status

Recruiting

Conditions

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 Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 102206
        • Recruiting
        • Peking University International Hospital
        • Contact:
      • Beijing, Beijing, China, 100079
        • Recruiting
        • Beijing Tiantan Hospital, Capital Medical University
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Chunxue Wu, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
End of study (5-year) MRI scan
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.
End of study (3-year) MRI scan after surgery
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.
End of follow-up period (5-year)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
End of study (5-year) MRI scan
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.
End of study (5-year) MRI scan

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

yuanli Zhao

Collaborators

Peking University International Hospital

Investigators

  • Principal Investigator: Li Ma, MD, PhD, Beijing Tiantan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 3, 2019

Primary Completion (Anticipated)

December 31, 2026

Study Completion (Anticipated)

December 31, 2026

Study Registration Dates

First Submitted

August 29, 2019

First Submitted That Met QC Criteria

August 30, 2019

First Posted (Actual)

September 3, 2019

Study Record Updates

Last Update Posted (Actual)

September 4, 2019

Last Update Submitted That Met QC Criteria

September 3, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KYSQ 2018-020-01
  • H0906 81801140 (Other Grant/Funding Number: National Nature Science Foundation)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Study Protocol to be published in peer-reviewed journal

IPD Sharing Time Frame

Since the publication of study protocol

IPD Sharing Access Criteria

Available from the principle investigator upon reasonable request

IPD Sharing Supporting Information Type

  • Study Protocol

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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