The Role of NaV1.8 in Human Pain Models - a Randomized, Placebo-controlled Crossover Microdosing Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Area Under the Curve (AUC): Capsaicin injection
研究概览
简要总结
This study aims to understand how NaV1.8, a specific type of sodium channel found in peripheral nerves, contributes to different types of pain in humans. To address this, suzetrigine, a highly selective blocker of the NaV1.8 channel, is used. While current pain medications often have side effects that limit their use, NaV1.8 is a promising target for new, non-opioid pain treatments because it is primarily located in the nerves that send pain signals to the brain.
This study is a randomised, placebo-controlled double-blind crossover microdosing trial. This means that very small, safe amounts of the drug are injected directly into the skin of healthy volunteers to observe its effects locally. This approach ensures the drug works only at the injection site with negligible exposure to the rest of the body.
Healthy volunteers will undergo six different types of brief, controlled pain tests to see which ones are reduced by blocking NaV1.8.
These tests are as follows:
- Electrical stimulation: Brief electrical pulses delivered onto the skin.
- Mechanical stimulation: A standardised "pin-prick" stimulation of the skin.
- Chemical stimulation: An injection of fluid containing capsaicin (the active component of chilli peppers) superficially into the skin.
- Heat stimulation: An injection of hot fluid superficially into the skin.
- Cold stimulation: An injection of cold fluid superficially into the skin.
- Acid stimulation: An injection of acidic fluid superficially into the skin.
By comparing the effects of suzetrigine against a placebo and a standard local anaesthetic (lidocaine), the study will help determine which specific pain modalities critically depend on NaV1.8.
详细描述
Study Objective:
The primary objective of this trial is to evaluate the analgesic efficacy of selective NaV1.8 inhibition across multiple established experimental human pain models. While selective NaV1.8 inhibitors like suzetrigine have demonstrated success in clinical trials for acute post-surgical pain, it remains unknown whether their efficacy is modality-specific in humans. This study seeks to bridge that gap by testing mechanical, electrical, chemical, and thermal pain induction.
Study Design:
This is a randomised, placebo-controlled double-blind crossover microdosing trial involving healthy volunteers. To isolate the role of NaV1.8 without systemic side effects, the study utilises an intracutaneous microdosing approach. Suzetrigine (1 µM) is administered via local injection, providing an effective local concentration while resulting in a total dose (~1.53 µg) that is approximately 32,000-fold lower than therapeutic oral doses.
Methodology and Pain Modalities:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 70 years
- •Full legal capacity
排除标准
- •Participant of another study, ongoing or within the last 4 weeks
- •Medication intake (except contraception) or drug abuse
- •Female subjects: Positive pregnancy test or breastfeeding
- •Verified body temperature above 38°C
- •Known allergic diseases, in particular asthmatic disorders
- •Limited accessibility of forearms (e.g. orthopedic cast)
- •Sensory deficit, skin disease or hematoma at the forarms
研究组 & 干预措施
Control solution
Participants receive intracutaneous injections of control solution (negative control) before or during experimental pain induction across six different modalities (electrical, mechanical, capsaicin, heat, and cold).
干预措施: Control Solution (Drug)
Lidocaine
Participants receive intracutaneous injections of lidocaine (positive control) at a concentration of 2 mM before or during experimental pain induction across three out of six different modalities (electrical, mechanical, capsaicin).
干预措施: Lidocaine (drug) (Drug)
Suzetrigine
Participants receive intracutaneous injections of suzetrigine at a concentration of 1 µM before or during experimental pain induction across six different modalities (electrical, mechanical, capsaicin, acid, heat, and cold).
干预措施: Suzetrigine (Drug)
结局指标
主要结局
Area Under the Curve (AUC): Capsaicin injection
时间窗: From injection until 0 pain for 30s.
Metric: Numerical Rating Scale (0-100). Calculation: The AUC of pain ratings provided every 5 seconds, starting from the time of injection until a consecutive rating of 0 is maintained for 30 seconds.
Pain Intensity: Electrical stimulation
时间窗: 1.5 minutes post-injection.
Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The average of all provided pain ratings divided by the number of delivered stimuli (maximum of 23 stimuli). If a subject stops the test upon reaching a rating of 30, the average is calculated based on the actual number of stimuli delivered.
Geometric Mean Pain Intensity: Mechanical stimulation
时间窗: 1.5 minutes post-injection.
Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The geometric mean of the pain ratings recorded from three standardized mechanical stimuli (3.6N force).
Area Under the Curve (AUC): Acid injection
时间窗: 110 seconds
Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The AUC of pain ratings provided every 5 seconds during the pH decrease from 7.2 to 5.4.
Area Under the Curve (AUC): Heat injection
时间窗: 150 seconds
Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The AUC of pain ratings provided every 5 seconds during the temperature increase from 23°C to 52°C.
Area Under the Curve (AUC): Cold injection
时间窗: 150 seconds
Metric: Numerical Rating Scale (0-100; 0=No pain, 100=Worst imaginable pain). Calculation: The AUC of pain ratings provided every 5 seconds during the temperature decrease from 23°C to 4°C.
次要结局
未报告次要终点
研究者
Stefan Heber
Principal Investigator
Medical University of Vienna