A Double-blind, Randomized, Cross-over, Feasibility Trial of Pregabalin for the Treatment of Recessive Dystrophic Epidermolysis Bullosa-associated Neuropathic Pain and Itch
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Difference in the mean pain scores between pregabalin and placebo group: VAS
研究概览
简要总结
Recessive dystrophic epidermolysis bullosa (RDEB) patients' quality of life is severely affected by neuropathic pain and itch, which have recently been demonstrated to be secondary to skin small fiber neuropathy. To date, there is no evidence on what the best agent is to control these symptoms. Based on the anecdotal data and safety profile, the investigators believe that pregabalin is a therapeutic agent that will be effective and safe in this population. The investigators propose to conduct a blinded study, using pregabalin versus placebo in which each patient serves as its own control (cross-over design). This is a feasibility study that will provide preliminary data on efficacy and safety of pregabalin in RDEB patients with neuropathic pain and itch and gather much needed data (dosage, titration schedule, outcome measures, etc) to inform the design of a larger cohort, controlled, multicenter trial.
详细描述
Neuropathic pain and itch are significant symptoms that affect RDEB patients' quality of life. To date, there is no evidence on what the best agent is to control these symptoms.
Based on the anecdotal data and the safety profile, the investigator believes that pregabalin is a therapeutic agent that will be effective and safe in this population.
This is a pilot, randomized, double-blinded, cross-over trial of pregabalin vs placebo for the treatment of RDEB associated neuropathic pain and itch. The study will run for 24 weeks and will have 4 separate phases with 6 overall visits: 1. Observation/wash out period (2 weeks); 2. ARM-1, ½ of the patients will receive pregabalin(A) and ½ the placebo (B) (10 weeks); 3. Wash out period (2 weeks) and 4. ARM-2 (patients who received placebo will receive pregabalin and pregabalin will receive placebo (10 weeks).
Patients will be recruited during the regular clinic visits or invited to participate via a letter followed by 2 phone calls.
- Screening/Wash out period #1 (Visit 0)to assess eligibility criteria and the background pain and itch level (2 weeks), as well as the effectiveness of patients' "standard pain/itch interventions". Throughout this phase and the rest of the study, patients will receive pain and itch medications, except those that interfere with the pregabalin (see exclusion criteria).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All investigators, assessors and participants will be blinded to the intervention. The randomization will be done by the research pharmacist. Unblinding before the study completion is allowed only in case of serious adverse events.
入排标准
- 年龄范围
- 8 Years 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: > 8 - 40 years (we selected this range due to lack of data in younger population and the difficulty in getting patient reported outcomes in younger patients)
- •Diagnosis of RDEB (by a dermatologist and/or EB specialist and/or genetic confirmation)
- •Evidence of neuropathy defined by: thermal sensory loss (determined by a thermal roller, ROLLTEMP2, Sometic, Sweden) 14 and > 4/10 score using a screening tool for neuropathic pain, the DN4 questionnaire 15
- •Pain intensity of > 4/10 on a 0-10 VAS scale measured daily (reduced frequency is also acceptable) at night over 2 weeks
- •Itch intensity of > 4/10 on a 0-10 VAS scale measures daily (reduced frequency is also acceptable) at night over 2 weeks
- •Consent to follow with study procedures
排除标准
- •Intolerance and/or allergy to Pregabalin or gabapentin
- •Lactose intolerance (placebo capsules contain lactose)
- •Pregabalin use within 2 weeks before study enrolment
- •Ongoing treatment with gabapentin, amitriptyline, duloxetine, nortriptyline, other tricyclics or SNRIs
- •Medical conditions that would be considered as contraindications for pregabalin treatment (ischemic heart disease, cardiac dysrhythmia, glaucoma, history of urinary retention)
- •Pregnancy
- •History of use of restrictive substances or alcohol abuse
- •Allergy to gelatin
研究组 & 干预措施
Pregabalin followed by placebo
The study has a crossover design. Participants in this arm will receive pregabalin during the first study treatment period for ten weeks and placebo during their second ten-week treatment period . The dose will depend on the participant's weight and phase of treatment period. Each treatment period consists of 4 weeks of escalating dose until the desired maximum , 4 weeks of active treatment and 2 weeks of titrating down.
干预措施: Pregabalin (Drug)
Placebo followed by Pregabalin
Participants will receive placebo during the first treatment period of the study(10 weeks) followed by 10 weeks of pregabalin treatment . The dose will depend on the participant's weight and phase of the treatment period . Each treatment period consists of 3 phases: 4 weeks of escalating dose until the desired maximum, 4 weeks of active treatment and 2 weeks of titrating down.
干预措施: Pregabalin (Drug)
结局指标
主要结局
Difference in the mean pain scores between pregabalin and placebo group: VAS
时间窗: 12 weeks
It will be measured as difference in the mean pain values pre- and post-intervention for each group using the Visual Analog Scale (VAS).It is a 10 cm line with anchor statements on the left (no pain) and on the right (worst pain ever). The patient is asked to mark their pain level on the line.The pain is scored using the VAS by measuring the distance in centimeters (0-10) from the "no pain" anchoring point.
次要结局
- Proportion of patients on pregabalin achieving a ≥50% reduction in their mean pain intensity score across last 7 days of treatment compared to baseline/wash-out(12 weeks)
- Proportion of patients on pregabalin achieving a ≥75% reduction in their mean pain intensity score across last 7 days of treatment compared to baseline/wash-out(12 weeks)
- Difference in the average pain score assessed using VAS between first and second treatment periods (period effect)(24 weeks)
- Proportion of patients on pregabalin achieving a ≥75% reduction in their mean itch intensity score across last 7 days of treatment compared to baseline/wash-out(24 weeks)
- Proportion of patients on pregabalin achieving a ≥50% reduction in their mean itch intensity score across last 7 days of treatment compared to baseline/wash-out(12 weerks)
- Difference in the average itch score as assessed using VAS between the first and the second treatment periods (period effect).(24 weeks)
- Changes in the Quality of Life in Epidermolysis Bullosa Questionnaire score(QOLEB) for patients >18yrs in the intervention versus placebo(24 weeks)
- Changes in iscorEB (instrument for scoring clinical outcomes for research of EB), patient portion score in the intervention versus placebo(24 weeks)
研究者
Elena Pope
Dermatology section head
The Hospital for Sick Children