Efficacy of Gabapentin in Treating Pain in Children With Severe Neurological Impairment
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Mean pain and irritability score
研究概览
简要总结
Children born with severe brain-based developmental disabilities frequently experience persistent unexplained periods of pain and irritability, often compounded by a limited capacity to communicate their distress. The investigators call this entity Pain and Irritability of Unknown Origin (PIUO). The rationale of this trial is to identify the clinical effect size of gabapentin in reducing and resolving pain in children with developmental brain disorders, specifically those with severe neurological impairment (SNI).
详细描述
Background
Children with SNI may experience nociceptive-inflammatory pain as a result of their specific medical condition or procedures. Often, however, it is not clear what underlies the pain behavior as there is no clear inciting noxious event. The investigators define this entity of pain without an obvious source as Pain and Irritability of Unknown Origin (PIUO).
The investigators' work to date has developed an efficient, focused clinical pathway to evaluate children with SNI for all potential sources of nociceptive-inflammatory pain. Using this approach the "unknown" element of pain in these children is reduced and a source of PIUO may be found in individual cases, increasing the potential for treatment. Nevertheless there are children, who at the end of a thorough evaluation guided by a clinical pathway, will still have PIUO. These children may benefit from adjuvant analgesics such as gabapentin.
The evidence base supporting the use of gabapentin for pain and irritability in infants and children with neurological impairment rests on case series publications describing a limited number of retrospective cases. The lack of prospective, randomized studies, even for this commonly used medication, underpins the rationale for this trial.
Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Both active drug and placebo will be masked in a liquid formulation, and administered via the same route (oral, direct gastric route, or direct jejunal route) depending on the subject's usual feeding approach. The label applied to the bottle will be blinded and identical flavouring will be added to the drug and placebo for additional masking.
入排标准
- 年龄范围
- 6 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged 6 months to 18 years with SNI (from any cause) with unexplained pain and irritability and whose cognitive or communication impairments prevent determination of pain location, cause, and type will be eligible to participate.
- •Eligible children will have cognitive impairment or be non-verbal and have severe levels of disability equivalent to Gross Motor Functional Classification System (GMFCS) scores of 3, 4 or 5 as well as Communication Function Classification System (CFCS) level 4 or
- •Eligible children will score >3 on two scales administered via an Eligibility Screening that measures persistence and distress level the child is experiencing as well as identifies the type of pain and irritability as PIUO - with no obvious cause or explanation. The score of >3 on the scale measuring pain persistence and distress level confirms that the child is experiencing pain and irritability more than "a little" on "some days".
- •The will be evidence of a comprehensive evaluation of PIUO in the child's medical history, showing no evidence for treatable sources (nociceptive-inflammatory) of pain and/or irritability symptoms.
排除标准
- •Children not within the specified age range
- •Children with communication capabilities and cognitive development to localize their pain.
- •Participants whose pain and or irritability is diagnosed through completion of the PIUO Pathway during the enrollment phase of the trial.
- •Patients with a known hypersensitivity/allergy to the study medication
- •Patients who are actively participating in another experimental therapy study for pain and/or irritability.
- •Patients who are a poor medical risk because of other systemic diseases or active uncontrolled infections.
- •Patients who score A or B on the Pain Survey
- •Patients who have an active source of nociceptive-inflammatory pain at the time of enrolment (e.g., post-operative pain)
- •Patients with active renal disease, known renal impairment or glomerular filtration rate < 60 mL/min/1.73 m2 (if known).
- •Patients with known significant hepatic impairment at the discretion of the investigator.
- •Patients with clinically relevant abnormal ECG (if available) at the discretion of the investigator.
- •Patients with diagnosis of sickle cell disease.
- •Parents who do not speak one of Canada's two official languages (English or French)
研究组 & 干预措施
Medication
Gabapentin is clinically started at a low dose and titrated to clinical effect or maximum target dose, whichever is lower.
The starting dose of gabapentin will be 5 mg/kg administered as oral liquid or via gastric or jejunal routes. On Day 1 of the study, the gabapentin will be administered once at bedtime and then increased according to a preset schedule. The dose will be increased every 3rd - 4th day in a step wise fashion of 13% - 50%, starting with the evening dose in order to accommodate sedation. The maximum dose for subjects will be as follows: < 15 kg to 60 mg/kg day and ≥15 kg to 45 mg/kg/day.
干预措施: Gabapentin (Drug)
Placebo
Participants on this arm receive placebo, masked and dispensed according to the same preset schedule as the Medication arm.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean pain and irritability score
时间窗: Days 11-19
The mean pain and irritability score on the Non-Communicating Children's Pain Checklist Revised (NCCPC-R) on active drug compared to placebo.
次要结局
- Identification of lowest effective dose(Days 11-19 on active drug)
- Maximal effect dosage(Days 11-19 on active drug)
- Identification of latency time(Days 0-19)
- Adverse Events collection(Through Sequence 1 and 2, total of 55 days)
研究者
Harold Siden
Principal Investigator
University of British Columbia