The Safety of High Dose Minocycline in the Patient Population Undergoing Carotid Revascularization. A Phase I Study
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Drug Safety/Tolerability (Number of patients that require discontinuation of drug because of side effects)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of high-dose minocycline in the patient population undergoing carotid revascularization procedures, namely carotid endarterectomy (CEA) and carotid artery stenting (CAS). Establishment of safety will facilitate proceeding to a phase II trial.
During this trial, patients undergoing carotid revascularization procedures will receive high doses of minocycline with the following schedule (based on previous trials):
- Day prior to procedure: 800mg orally (p.o), 700mg p.o.
- Day of procedure: 600mg intravenously( i.v.), 500mg p.o.
- Day after procedure: 400mg p.o., 400mg p.o.
The levels of the drug in the plasma, standard blood tests (complete blood count, creatinine, liver function tests) as well as markers of neuronal injury (Neuron specific enolase, protein- S100b) and inflammation (C-reactive protein) will also be monitored. The patients will be monitored closely for the development of side effects from minocycline.
MRI imaging will be used to follow the development of small strokes as a result of the revascularization procedures and their resolution. The patients of this study, all receiving peri-operative minocycline, will be compared with historical controls with regards to development of small strokes and persistent of these strokes on subsequent MRI imaging.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a clinical indication for carotid revascularization (CRV) as decided by the treating physicians (the clinical indications for CRV as well as the choice of the type of CRV, either CEA or CAS, will be entirely up to the treating physicians)
- •Patients who can perform the neurocognitive tests in English
- •Women of childbearing age who are non-lactating and have a negative pregnancy test
- •Patients in the age range of 18 years - 90 years
- •Patients able to undergo MRI imaging.
- •Patients that are dependable and able to return for follow-up studies and exams.
- •Patients that will be in the hospital (inpatients) the day prior to the procedure for clinical purposes (for evaluation of side effects from the first dose and for overnight infusion of minocycline before the procedure)
排除标准
- •Known hypersensitivity to tetracyclines
- •Significant neurological deficit including but not limited to dense aphasia, hemi- or mono-paresis (motor strength equal or less than 3/5) or neglect.
- •Baseline abnormalities on the MRI of the brain which would preclude the detection of new DWI or FLAIR changes. (e.g large areas of acute stroke, large areas of previous encephalomalacia, existing hardware such as aneurysm clips or coil masses etc.)
- •Patients who are pregnant, breast-feeding, or lactating.
- •Patients with a contraindication to undergo MRI, including those with pacemakers, metal implants and metal fragments within their bodies.
- •Patients with abnormal liver function tests at baseline defined as a 2-fold elevation in alanine-aminotransferase.
- •Patients with significantly affected renal function at baseline (Creatinine equal or above 2mg/dL).
- •Patients on high dose isotretinoin, vitamin A, or methotrexate
- •Patients undergoing emergency carotid revascularization procedures.
- •Any clinically important known medical, surgical, psychiatric or psychological disease, which would preclude completion of the protocol (such as advanced cardiac, renal or pulmonary disease).We will screen for physical and mental capacity to undergo study procedures and will obtain proxy consent for subjects who appear decisionally impaired. The screening process will be performed by the physician co-investigator obtaining the informed consent.
- •Patients with a Mini-Mental Status Exam score (MMSE) of less than 21 (as determined by one of the co-investigators). Patients with MMSE score of 21 will be included.
- •Patients undergoing carotid revascularization in less than 36 hours from identification, or patients who are undecided about participation less than 36 hours prior to the procedure will not be eligible for the study.
- •Patients with any other factor that would make follow-up studies difficult (e.g patient is from another country, or patient is a prisoner)
研究组 & 干预措施
Administration of minocycline
All patients in the study will receive minocycline periprocedurally with the following schedule:
- Day prior to procedure: 800mg p.o., 700mg p.o.
- Day of procedure: 600mg i.v., 500mg p.o.
- Day after procedure: 400mg p.o., 400mg p.o.
干预措施: Administration of minocycline (Drug)
结局指标
主要结局
Drug Safety/Tolerability (Number of patients that require discontinuation of drug because of side effects)
时间窗: One day prior to procedure to 1 days after procedure
The primary aim of this phase I study is to establish the safety and tolerability of this drug in patient population undergoing carotid revascularization procedures by monitoring complete blood counts, liver enzymes, renal function tests, and clinical side effects During the above time frame (one day prior to procedure until 1 day after the procedure) the number of patients that develop any side effects requiring discontinuation of the drug will be noted. Side effects that will lead to discontinuation of the drug are the following: * The patient reports a clinical side effect as intolerable (nausea /vomiting, dysphagia, rash, vertigo or other side effects attributable to the administration of minocycline) * Change in liver function tests ( 2 times elevation of alanine-aminotransferase above the normal range) * Change in renal function tests (creatinine more than 1.5 points from baseline)
次要结局
- Progression of procedural stroke on MRI imaging(10 days before procedure, 1 day after procedure, 1 month after procedure)
- Neuropsychological test performance(10 days prior to procedure, 1 day after procedure, 1 month after procedure)
- Myocardial Infarction(Days 1, 2(procedure day), 3)
- Markers of neuronal injury(1 day prior to procedure, 1 day after the procedure, 1 month after the procedure)
研究者
Georgios Zenonos
Neurosurgery Resident, University of Pittsburgh Medical Center
University of Pittsburgh