Peripheral KV7 Activation for Pain Relief - A Randomized, Placebo-Controlled Crossover Microdosing Trial Using Flupirtine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Pain intensity over time (area under the curve, AUC) after intradermal capsaicin or heat stimulus ± Flupirtine
研究概览
简要总结
The goal of this clinical trial is to learn if the drug Flupirtine can safely lower pain when used in tiny amounts directly in the skin. The study will test whether Flupirtine works by activating specific nerve channels in the skin called KV7 potassium channels. These channels help control how pain signals travel to the brain.
The main questions the study aims to answer are:
- Does Flupirtine lower pain caused by capsaicin, the active ingredient in chili peppers?
- Does Flupirtine lower pain caused by heat?
Researchers will compare Flupirtine to a placebo (a look-alike injection that does not contain any drug) to see if Flupirtine lowers pain better than the placebo.
Participants will:
- Receive tiny skin injections that contain either Flupirtine, capsaicin, heat, or placebo
- Rate their pain on a scale from 0 (no pain) to 100 (worst pain imaginable)
- Complete all study procedures during one visit that lasts about 1 hour
Only a small amount of Flupirtine will be used in this study-less than 1/800 of the usual dose. The drug is injected into the skin, not taken by mouth. Because of this, the risk of side effects is extremely low.
This study includes healthy adults between the ages of 18 and 70. It does not include people who are pregnant, taking medications, or who have skin or nerve problems.
The goal is to find out if Flupirtine can be used in the future to treat pain in a new way-by working directly in the skin and not in the brain. This could help avoid side effects like tiredness or dizziness.
The study is sponsored by the Medical University of Vienna and follows all safety and ethical rules.
详细描述
This randomized, placebo-controlled crossover clinical trial investigates whether a very small (microdose) amount of the drug Flupirtine, when injected directly into the skin, can reduce pain caused by chemical and heat-based stimuli. The research is based on the hypothesis that activating KV7 potassium channels in peripheral sensory nerves can lower pain without involving the central nervous system (brain and spinal cord), potentially offering a new class of non-opioid analgesics with fewer side effects.
Background and Rationale
Pain is the leading reason why people seek medical care. While several types of pain medications exist-such as non-opioid and opioid analgesics, antidepressants, anticonvulsants, and local anesthetics-many have limitations due to side effects, addiction risks, or limited effectiveness in certain pain types. New strategies for safe, targeted pain relief are urgently needed.
Recent research highlights KV7 channels, a group of voltage-gated potassium channels, as promising targets for pain modulation. These channels are expressed in peripheral sensory neurons, including nociceptors in the skin. When activated, they make it less likely for the neuron to send pain signals to the brain. Preclinical studies in animals have shown that activating these channels-particularly the KV7.2/7.3 subtypes-can reduce pain.
Flupirtine, a previously approved non-opioid analgesic, is known to activate KV7 channels. Although it was withdrawn from the market due to rare cases of liver toxicity after long-term, high-dose systemic use, its mechanism of action remains of high scientific interest. Importantly, prior studies suggest that Flupirtine's pain-relieving effects may occur, at least in part, through peripheral activation of KV7 channels.
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)
盲法说明
To ensure double-blind conditions, all syringes are prepared and numbered by an independent laboratory technician who is not involved in the experiment. Both the participants and the experimenter are blinded to the injected substance (e.g., Flupirtine, placebo, or capsaicin combinations). Due to technical limitations, blinding of the experimenter to the temperature of injected fluid is not possible; therefore, the room-temperature injection in the heat condition is single-blind. Familiarization injections are administered unblinded for safety and tolerability assessment. Blinding is maintained until the end of each subject's participation. Randomization sequences are generated and stored separately and are only accessible to unblinded personnel in case of emergency.
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 To ensure an equal number of each sex in the study population, only volunteers of one sex will be included as soon as the number of subjects with the other sex has reached half of the calculated sample size.
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
- •Body temperature above 38°C, diagnostically verified
- •Known allergic diseases, in particular asthmatic disorders and skin diseases
- •Sensory deficit, skin disease or hematoma of unknown origin in examination of the test site
研究组 & 干预措施
Capsaicin Sequence A
Participants receive six intradermal injections in the following order:
- Capsaicin 7.6 ng
- Capsaicin + Flupirtine 0.5 µg
- Capsaicin + Flupirtine 1.2 µg
- Capsaicin + Flupirtine 3.0 µg
- Capsaicin + Flupirtine 7.6 µg
- Placebo (SIF only) Pain is rated every 5 seconds. Each injection is blinded and separated by ≥3 cm.
干预措施: Capsaicin only (7.6 ng) (Drug)
Capsaicin Sequence A
Participants receive six intradermal injections in the following order:
- Capsaicin 7.6 ng
- Capsaicin + Flupirtine 0.5 µg
- Capsaicin + Flupirtine 1.2 µg
- Capsaicin + Flupirtine 3.0 µg
- Capsaicin + Flupirtine 7.6 µg
- Placebo (SIF only) Pain is rated every 5 seconds. Each injection is blinded and separated by ≥3 cm.
干预措施: Capsaicin + Flupirtine 0.5 µg (Drug)
Capsaicin Sequence A
Participants receive six intradermal injections in the following order:
- Capsaicin 7.6 ng
- Capsaicin + Flupirtine 0.5 µg
- Capsaicin + Flupirtine 1.2 µg
- Capsaicin + Flupirtine 3.0 µg
- Capsaicin + Flupirtine 7.6 µg
- Placebo (SIF only) Pain is rated every 5 seconds. Each injection is blinded and separated by ≥3 cm.
干预措施: Capsaicin + Flupirtine 1.2 µg (Drug)
Capsaicin Sequence A
Participants receive six intradermal injections in the following order:
- Capsaicin 7.6 ng
- Capsaicin + Flupirtine 0.5 µg
- Capsaicin + Flupirtine 1.2 µg
- Capsaicin + Flupirtine 3.0 µg
- Capsaicin + Flupirtine 7.6 µg
- Placebo (SIF only) Pain is rated every 5 seconds. Each injection is blinded and separated by ≥3 cm.
干预措施: Capsaicin + Flupirtine 3.0 µg (Drug)
Capsaicin Sequence A
Participants receive six intradermal injections in the following order:
- Capsaicin 7.6 ng
- Capsaicin + Flupirtine 0.5 µg
- Capsaicin + Flupirtine 1.2 µg
- Capsaicin + Flupirtine 3.0 µg
- Capsaicin + Flupirtine 7.6 µg
- Placebo (SIF only) Pain is rated every 5 seconds. Each injection is blinded and separated by ≥3 cm.
干预措施: Capsaicin + Flupirtine 7.6 µg (Drug)
Capsaicin Sequence A
Participants receive six intradermal injections in the following order:
- Capsaicin 7.6 ng
- Capsaicin + Flupirtine 0.5 µg
- Capsaicin + Flupirtine 1.2 µg
- Capsaicin + Flupirtine 3.0 µg
- Capsaicin + Flupirtine 7.6 µg
- Placebo (SIF only) Pain is rated every 5 seconds. Each injection is blinded and separated by ≥3 cm.
干预措施: Placebo (SIF only, no capsaicin or Flupirtine) (Drug)
Capsaicin Sequence B
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin only (7.6 ng) (Drug)
Capsaicin Sequence B
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 0.5 µg (Drug)
Capsaicin Sequence B
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 1.2 µg (Drug)
Capsaicin Sequence B
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 3.0 µg (Drug)
Capsaicin Sequence B
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 7.6 µg (Drug)
Capsaicin Sequence B
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Placebo (SIF only, no capsaicin or Flupirtine) (Drug)
Capsaicin Sequence C
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin only (7.6 ng) (Drug)
Capsaicin Sequence C
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 0.5 µg (Drug)
Capsaicin Sequence C
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 1.2 µg (Drug)
Capsaicin Sequence C
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 3.0 µg (Drug)
Capsaicin Sequence C
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 7.6 µg (Drug)
Capsaicin Sequence C
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Placebo (SIF only, no capsaicin or Flupirtine) (Drug)
Capsaicin Sequence D
Same interventions as Sequence A but in a different randomized order according to Williams design.
干预措施: Capsaicin only (7.6 ng) (Drug)
Capsaicin Sequence D
Same interventions as Sequence A but in a different randomized order according to Williams design.
干预措施: Capsaicin + Flupirtine 0.5 µg (Drug)
Capsaicin Sequence D
Same interventions as Sequence A but in a different randomized order according to Williams design.
干预措施: Capsaicin + Flupirtine 1.2 µg (Drug)
Capsaicin Sequence D
Same interventions as Sequence A but in a different randomized order according to Williams design.
干预措施: Capsaicin + Flupirtine 3.0 µg (Drug)
Capsaicin Sequence D
Same interventions as Sequence A but in a different randomized order according to Williams design.
干预措施: Capsaicin + Flupirtine 7.6 µg (Drug)
Capsaicin Sequence D
Same interventions as Sequence A but in a different randomized order according to Williams design.
干预措施: Placebo (SIF only, no capsaicin or Flupirtine) (Drug)
Capsaicin Sequence E
Same interventions as Sequence A but in a different order according to Williams design
干预措施: Capsaicin only (7.6 ng) (Drug)
Capsaicin Sequence E
Same interventions as Sequence A but in a different order according to Williams design
干预措施: Capsaicin + Flupirtine 0.5 µg (Drug)
Capsaicin Sequence E
Same interventions as Sequence A but in a different order according to Williams design
干预措施: Capsaicin + Flupirtine 1.2 µg (Drug)
Capsaicin Sequence E
Same interventions as Sequence A but in a different order according to Williams design
干预措施: Capsaicin + Flupirtine 3.0 µg (Drug)
Capsaicin Sequence E
Same interventions as Sequence A but in a different order according to Williams design
干预措施: Capsaicin + Flupirtine 7.6 µg (Drug)
Capsaicin Sequence E
Same interventions as Sequence A but in a different order according to Williams design
干预措施: Placebo (SIF only, no capsaicin or Flupirtine) (Drug)
Capsaicin Sequence F
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin only (7.6 ng) (Drug)
Capsaicin Sequence F
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 0.5 µg (Drug)
Capsaicin Sequence F
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 1.2 µg (Drug)
Capsaicin Sequence F
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 3.0 µg (Drug)
Capsaicin Sequence F
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Capsaicin + Flupirtine 7.6 µg (Drug)
Capsaicin Sequence F
Same interventions as Sequence A but in a different order according to Williams design.
干预措施: Placebo (SIF only, no capsaicin or Flupirtine) (Drug)
Heat Sequence A
Participants receive three slow increasingly warm intradermal injections in the following order:
- Room temperature SIF (control)
- Heated SIF (placebo)
- Heated SIF + Flupirtine 124 µg Injections are randomized using a Williams design. Pain is rated every 5 seconds until 6 consecutive zeros.
干预措施: Room Temperature Injection (Control) (Drug)
Heat Sequence A
Participants receive three slow increasingly warm intradermal injections in the following order:
- Room temperature SIF (control)
- Heated SIF (placebo)
- Heated SIF + Flupirtine 124 µg Injections are randomized using a Williams design. Pain is rated every 5 seconds until 6 consecutive zeros.
干预措施: Heated injection without Flupirtine (Drug)
Heat Sequence A
Participants receive three slow increasingly warm intradermal injections in the following order:
- Room temperature SIF (control)
- Heated SIF (placebo)
- Heated SIF + Flupirtine 124 µg Injections are randomized using a Williams design. Pain is rated every 5 seconds until 6 consecutive zeros.
干预措施: Heated Injection with Flupirtine 124 µg (Drug)
Heat Sequence B
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Room Temperature Injection (Control) (Drug)
Heat Sequence B
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Heated injection without Flupirtine (Drug)
Heat Sequence B
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Heated Injection with Flupirtine 124 µg (Drug)
Heat Sequence C
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Room Temperature Injection (Control) (Drug)
Heat Sequence C
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Heated injection without Flupirtine (Drug)
Heat Sequence C
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Heated Injection with Flupirtine 124 µg (Drug)
Heat Sequence D
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Room Temperature Injection (Control) (Drug)
Heat Sequence D
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Heated injection without Flupirtine (Drug)
Heat Sequence D
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Heated Injection with Flupirtine 124 µg (Drug)
Heat Sequence E
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Room Temperature Injection (Control) (Drug)
Heat Sequence E
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Heated injection without Flupirtine (Drug)
Heat Sequence E
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Heated Injection with Flupirtine 124 µg (Drug)
Heat Sequence F
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Room Temperature Injection (Control) (Drug)
Heat Sequence F
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Heated injection without Flupirtine (Drug)
Heat Sequence F
Same injections as Heat Sequence A, administered in a different order according to Williams design.
干预措施: Heated Injection with Flupirtine 124 µg (Drug)
结局指标
主要结局
Pain intensity over time (area under the curve, AUC) after intradermal capsaicin or heat stimulus ± Flupirtine
时间窗: Immediately post-injection, up to 3 minutes on Day 1
Pain is rated every 5 seconds using a numerical rating scale from 0 (no pain) to 100 (worst imaginable pain). Ratings continue until the participant reports zero pain for 30 consecutive seconds. For each injection, the area under the curve (AUC) of pain intensity over time is calculated. The primary outcome is the difference in pain AUC between Flupirtine-treated and placebo-treated conditions in both the capsaicin and heat models.
次要结局
未报告次要终点
研究者
Stefan Heber
Principal investigator
Medical University of Vienna