Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- description of the safety profile of mangafodipir administration in patients with epilepsy
研究概览
简要总结
Background:
- The blood-brain barrier separates the brain from the rest of the body. Epilepsy is a neurological disease that causes seizures. It can affect this barrier. Researchers think a contrast agent called mangafodipir might be better able to show areas of the brain that epilepsy affects.
Objective:
- To see if mangafodipir is well tolerated and safe. To see if magnetic resonance imaging (MRI) using either mangafodipir or gadolinium can show areas of blood-brain barrier breakdown in people with epilepsy.
Eligibility:
- People ages 18-60 who:
- Have epilepsy not controlled by drugs
- Prior or concurrent enrollment in 18-N-0066 is required
Design:
- Participants will be screened with:
- Medical history
- Physical exam
- Blood and urine tests
- Participants will have up to 6 visits in 1-3 months. One visit is an inpatient stay lasting 2-10 days. Visits may include:
- Video-EEG monitoring for participants with epilepsy
- An IV catheter put in place: a needle guides a thin plastic tube into an arm vein.
- Getting mangafodipir through the IV.
- Getting gadolinium through the IV.
- Up to 6 MRI scans over a 10-day period: a magnetic field and radio waves take pictures of the brain. Participants lie on a table that slides into a metal cylinder. They are in the cylinder for 45-90 minutes, lying still for up to 10 minutes at a time. The scanner makes loud knocking sounds. Participants will get earplugs.
- A final MRI at least 2 weeks after receiving mangafodipir....
详细描述
Objective:
The primary goals of this pilot study are to (1) describe the safety profile of administration of mangafodipir in patients with epilepsy and (2) investigate the prevalence of blood-brain barrier disruption (BBBD) in patients with drug-resistant focal epilepsy using peri-ictal manganese enhanced magnetic resonance imaging (MEMRI) and interictal gadolinium dynamic contrast-enhanced MRI (DCE-MRI) and determine if these methods will allow for visualization of seizure foci. Secondary objectives are further exploration of MEMRI and DCE-MRI properties in patients with epilepsy.
Study population:
40 patients with drug-resistant epilepsy.
Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •Able to give written informed consent directly.
- •Drug resistant epilepsy participants will be defined as having clinically documented seizures with consistent EEG evidence as defined by the 1981 International Classification of Epileptic Seizures, refractory to standard anti-seizure treatment for at least one year prior to enrolling in this study and with an average of at least one seizure per month. This criterion will be established by preliminary screening NINDS Epilepsy Service under protocol 18-N-
- •Seizure focus localization will be determined by standard clinical, neurophysiologic, and imaging studies. Prior or concurrent enrollment in 18-N-0066 is required.
排除标准
- •General exclusions:
- •Patients with epilepsy who are not surgical candidates
- •Significant structural brain abnormality such as a brain tumor, stroke, brain damage from head trauma or blood vessel abnormalities, on the baseline MRI scan.
- •Positive test for HIV
- •Pregnancy or breast-feeding
- •Claustrophobia to a degree that the subject would feel uncomfortable in the MRI machine.
- •Cannot lie on their back for at least two hours.
- •Risk for MRI scan, (e.g., any non-organic implant or other device such as a cardiac pacemaker or infusion pump or other metallic implants, objects or body piercings that cannot be removed, or history of being a welder or metal worker due to small metal fragments in the eye)
- •Unwilling to allow sharing and/or use in future studies of coded data that are collected for this study
- •MEMRI component specific exclusions (applicable only to patients participating in this arm of the study):
- •History of post-ictal psychosis or post-ictal aggression
- •Planning to get pregnant in the next 2 months
- •History of clinically significant liver or kidney disease that could potentially increase the risk of CNS damage due to manganese exposure
- •A history of drug or alcohol abuse/dependence (subjects scoring 8 or higher on the AUDIT scale)
- •Screening lab abnormalities demonstrating values more than 2 times the upper limit of normal for AST, ALT, bilirubin, alkaline phosphatase, BUN, creatinine
- •Previous presumed occupational exposure to manganese (i.e., having worked in a mine, foundry, smelter, dry cell battery manufacturing facility, or agriculture)
- •Allergy to manganese
- •On-going treatment with calcium-channel blocker
- •Iron-deficiency anemia
- •Personal history of Parkinson s Disease or Parkinsonism or presence of this disease in a 1st degree relative
- •Gadolinium enhanced MRI component specific exclusions (applicable only to patients participating in this arm of the study):
- •Estimated GFR <60, tested within 1 week of scan
- •Allergy to gadolinium
- •Of note, patients who are ineligible for one arm of the study may still be eligible for and participate in the other arm of the study.
研究组 & 干预措施
2
Patients will be given gadolinium contrast before 7T MRI.
干预措施: Gadolinium (Drug)
1
Patients will be given the manganese contrast before 3T MRI.
干预措施: Mangafodipir (Drug)
结局指标
主要结局
description of the safety profile of mangafodipir administration in patients with epilepsy
时间窗: after mangafodipir adminstration
safety profile
evaluation of the utility of MEMRI and/or DCE-MRI in identifying focal BBBD in the seizure onset zone identified by standard clinical, EEG, and imaging studies, and the homologous contralateral region.
时间窗: after mangafodipir and/or gadolinium administration
evaluation of the utility of MEMRI and/or DCE-MRI in identifying focal BBBD in the seizure onset zone identified by standard clinical, EEG, and imaging studies, and the homologous contralateral region.
次要结局
未报告次要终点