University of Alabama at Birmingham (UAB) Adult CBD Program
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Number of Participants With Severe Adverse Events (SAEs) (Increase in Seizure Frequency by More Than 100% Leading to Emergency Room Visit or Hospitalization).
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of Epidiolex at various doses between 5 mg/kg/day and 50 mg/kg/day as an additional (add-on) drug for treating debilitating, drug-resistant epilepsy.
详细描述
The specific goals of this phase 1 dose finding study, conducted in consecutively enrolled patients 18 years of age and older, are to prospectively and longitudinally assess the safety and tolerability, including cognitive effects, of Cannabidiol (CBD) at various doses between 5 mg/kg/day and 25 mg/kg/day, with additional titration in some cases up to 50 mg/kg/day. In order to participate in the study, participants will need to fulfill the inclusion and exclusion criteria.
The goal of the study is to fulfill the mandate of "Carly's Law" and to provide patients with debilitating epileptic conditions with access to CBD as an add-on treatment. Other care including routine neurological care unrelated to participation in the CBD study will need to be provided by patients' primary/current treating neurologist.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any patient with disabling epilepsy with diagnosis confirmed by video/EEG monitoring, and
- •Patient should have history of a trial of at least four anti-epileptic drugs (AEDs) including one trial of a combination of two concomitant AEDs, without successful seizure control. Vagus nerve stimulation (VNS), Responsive Neurostimulation (RNS) deep brain stimulation, or the ketogenic diet can be considered an equivalent to a drug trial,
- •Between 1-4 baseline anti-epileptic drugs at stable doses for a minimum of 4 weeks prior to submitting records for review by the CBD Treatment Approval Committee.
- •VNS or RNS must be on stable settings for a minimum of 3 months,
- •If on ketogenic diet, must be on stable ratio for a minimum of 3 months.
- •The referring provider needs to make available for review all of the following:
- •Most recent Brain MRI report,
- •Most recent ECG report,
- •Video/EEG monitoring report confirming the diagnosis of epilepsy,
- •Evidence that the patient has failed 4 AEDs as indicated above,
- •Current Medication List
- •Patient must have at least 4 clinically countable seizures per month.
- •Seizure history to include a documented history of generalized seizures (drop attacks, atonic, tonic-clonic and/or myoclonic), focal seizures without loss of consciousness with a motor component, focal seizures with loss of consciousness, or focal seizures with secondary generalization,
- •Results of routine testing including blood work (Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), Liver Function Tests (LFTs), renal panel, Urinary Analysis (UA), and levels of all AEDs) and digital copy of a routine EEG along with the formal written report performed within 3 months prior to submitting records for CBD Treatment Approval review. If any AED dose was adjusted within 3 months prior to submitting records for CBD Treatment Approval Committee review, level on the new dose will need to be provided. If applicable, results of any metabolic or genetic testing performed should be included in submitted records for review:
- •If applicable, documentation (including date of surgery) of prior VNS, RNS, Corpus Callosotomy, or other epilepsy surgery the patient has received.
- •Age 15 years and older,
- •Patients are able to keep and provide seizure calendar for at least 3 months prior to submitting records for CBD Treatment Approval Committee review. The patient will need to provide an updated calendar at the time of enrollment,
- •Acceptable method of contraception (or abstinence) for women of childbearing potential and for male patients with partners of childbearing potential; female patients must have a negative urine pregnancy test on the day of initiating CBD,
- •For patients who agree to participate in the optional neuroimaging sub-study, an MRI screen will be obtained to show that the patient does not have contraindication to receiving MRI/function MRI (fMRI) at 3 Tesla (e.g., metallic artifact).
- •Approval for inclusion by the CBD Treatment Approval Committee.
- •Current State of Alabama Resident
- •Acceptable documentation of Alabama residency includes the following:
- •a state issued identification (ID), such as a driver's license, from patient or patient's parent/legally authorized representative (LAR).
- •documents showing the patient or patient's parent/LAR rents/owns property in the state,
- •state voter registration from patient or patient's parent/LAR, or
- •a recent state tax return from patient or patient's parent/LAR.
排除标准
- •Active Psychogenic Non-Epileptic Seizures (PNES); Patients with more than 1 year freedom from PNES will not be excluded,
- •Patients who are pregnant, breastfeeding, or not using acceptable methods of contraception during the course of the study and for three months thereafter,
- •Male patient's partner is of child bearing potential; unless willing to ensure that they (male patients) or their partner(s) are using acceptable methods of contraception during the course of the study and for three months thereafter,
- •History of substance abuse/addiction,
- •Use of medical marijuana or CBD based product in the past 30 days,
- •Initiation of felbamate within last 12 months,
- •Allergy to CBD or any marijuana-type products,
- •Alanine Aminotransferase (ALT) >5 x Upper Limit of Normal (ULN) or Aspartate Aminotransferase (AST) >5 x ULN, as seen in participant's laboratory results submitted to the CBD Treatment Approval Committee for review.
- •Hemoglobin <10 or Hematocrit <30 or White Blood Count (WBC) < 2000, as seen in participant's laboratory results submitted to the CBD Treatment Approval Committee for review.
- •In investigator's judgment, active medical condition/treatment that impacts study activities.
- •Unable to provide consent (and no LAR),
- •Unable/Failure to comply with study visits/requirements and/or instructions,
- •Confirmed diagnosis for Dravet Syndrome or Lennox Gastaut Syndrome that qualifies the patient for a Greenwich (GW) Dravet Syndrome or Lennox Gastaut Syndrome randomized controlled clinical trial for which the patient is eligible pursuant to the GW clinical trial enrollment criteria unless
- •(a) there is no study that is either actively open for enrollment of patients at the University of Alabama at Birmingham (UAB) or that is expected to actively begin enrolling patients at UAB within two (2) months of the date on which the patient is screened for the UAB Pediatric CBD Program or UAB Adult CBD Program,
- •Subjects with contraindications to MRI/fMRI at 3 Tesla (e.g., metallic artifact) will not be offered participation in the optional substudy.
- •Primary residence in a State different than Alabama.
研究组 & 干预措施
Epidiolex 100 milligram/milliliter (mg/mL) oral solution
Participants will receive a CBD starting dose of 5 mg/kg/day in twice daily dosing and titrate by 5 mg/kg/2 weeks up to 25 mg/kg/day. Additional increases in dosing, by 5 mg/kg/day up to a maximum of 50 mg/kg/day, may be instituted at the discretion of the treating Principle Investigator (PI).
If a subject experiences a "clinically significant" or "dose limiting" adverse event (AE) or severe adverse event (SAE) attributable to CBD, the investigator will determine if a dose reduction or taper is necessary (decreases will occur in 5 mg/kg/2 week increments or at a rate felt appropriate by the treating PI).
干预措施: Epidiolex (Drug)
结局指标
主要结局
Number of Participants With Severe Adverse Events (SAEs) (Increase in Seizure Frequency by More Than 100% Leading to Emergency Room Visit or Hospitalization).
时间窗: For 1 Year following Enrollment
Severe adverse events (SAEs) were defined as increase in seizure frequency by more than 100% leading to emergency room visit or hospitalization. During study clinic and phone visits, adverse and severe adverse event monitoring and reporting were assessed among all participants. Data was recorded and stored in the UAB RedCap System.
Number of Participants With Change in Resting Blood Pressure or Heart Rate by 25% if Considered Significant by Managing Neurologist.
时间窗: For 1 Year following Enrollment
During study clinic visits, participant vital signs, including blood pressure and heart rate, were collected. Data was recorded and stored in the UAB RedCap System. Clinically significant was determined by using the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. Adverse events categorized as a grade 3 or above were considered clinically significant. Adverse events grade 4 or above were considered severe adverse events.
Number of Participants With Change in Laboratory Tests Considered by Managing Neurologists as Clinically Significant.
时间窗: For 1 Year following Enrollment
During study clinic visits, participants received laboratory testing to assess for side effects and toxicity. Data was recorded and stored in the UAB RedCap System. Laboratory testing included Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP; included Liver Function Tests (LFTs) mainly looking at alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), Urine Analysis (UA), and Antiepileptic Drug (AED) levels. Clinically significant was determined by using the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03. Adverse events categorized as a grade 3 or above were considered clinically significant. Adverse events grade 4 or above were considered severe adverse events.
次要结局
- Change in Seizure Severity Measured by the Chalfont Seizure Severity Scale (Duncan & Sander, 1991, JNNP).(For 1 Year following Enrollment)
- Change in Seizure Frequency as Measured in Total Number of Seizures Per Month.(For 1 Year following Enrollment)
研究者
Jerzy P Szaflarski
Professor
University of Alabama at Birmingham