Peripheral KV7 Activation for Pain Relief

NCT06971250 | Completed Early Phase 1

• 1 other identifier: EK1385/2024
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pain

Keywords

KV7 potassium channels; Flupirtine; Pain modulation; Peripheral analgesia; Experimental pain model; Capsaicin; Microdosing; non-opioid pain treatment; heat pain

Outcome Measures

Primary Outcomes (1)

• Pain intensity over time (area under the curve, AUC) after intradermal capsaicin or heat stimulus ± Flupirtine

  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.

  Immediately post-injection, up to 3 minutes on Day 1

Study Arms (12)

Capsaicin Sequence A

EXPERIMENTAL

Participants receive six intradermal injections in the following order: 1. Capsaicin 7.6 ng 2. Capsaicin + Flupirtine 0.5 µg 3. Capsaicin + Flupirtine 1.2 µg 4. Capsaicin + Flupirtine 3.0 µg 5. Capsaicin + Flupirtine 7.6 µg 6. Placebo (SIF only) Pain is rated every 5 seconds. Each injection is blinded and separated by ≥3 cm.

Drug: Capsaicin only (7.6 ng); Drug: Capsaicin + Flupirtine 0.5 µg; Drug: Capsaicin + Flupirtine 1.2 µg; Drug: Capsaicin + Flupirtine 3.0 µg; Drug: Capsaicin + Flupirtine 7.6 µg; Drug: Placebo (SIF only, no capsaicin or Flupirtine)

Capsaicin Sequence B

EXPERIMENTAL

Same interventions as Sequence A but in a different order according to Williams design.

Drug: Capsaicin only (7.6 ng); Drug: Capsaicin + Flupirtine 0.5 µg; Drug: Capsaicin + Flupirtine 1.2 µg; Drug: Capsaicin + Flupirtine 3.0 µg; Drug: Capsaicin + Flupirtine 7.6 µg; Drug: Placebo (SIF only, no capsaicin or Flupirtine)

Capsaicin Sequence C

EXPERIMENTAL

Same interventions as Sequence A but in a different order according to Williams design.

Drug: Capsaicin only (7.6 ng); Drug: Capsaicin + Flupirtine 0.5 µg; Drug: Capsaicin + Flupirtine 1.2 µg; Drug: Capsaicin + Flupirtine 3.0 µg; Drug: Capsaicin + Flupirtine 7.6 µg; Drug: Placebo (SIF only, no capsaicin or Flupirtine)

Capsaicin Sequence D

EXPERIMENTAL

Same interventions as Sequence A but in a different randomized order according to Williams design.

Drug: Capsaicin only (7.6 ng); Drug: Capsaicin + Flupirtine 0.5 µg; Drug: Capsaicin + Flupirtine 1.2 µg; Drug: Capsaicin + Flupirtine 3.0 µg; Drug: Capsaicin + Flupirtine 7.6 µg; Drug: Placebo (SIF only, no capsaicin or Flupirtine)

Capsaicin Sequence E

EXPERIMENTAL

Same interventions as Sequence A but in a different order according to Williams design

Drug: Capsaicin only (7.6 ng); Drug: Capsaicin + Flupirtine 0.5 µg; Drug: Capsaicin + Flupirtine 1.2 µg; Drug: Capsaicin + Flupirtine 3.0 µg; Drug: Capsaicin + Flupirtine 7.6 µg; Drug: Placebo (SIF only, no capsaicin or Flupirtine)

Capsaicin Sequence F

EXPERIMENTAL

Same interventions as Sequence A but in a different order according to Williams design.

Drug: Capsaicin only (7.6 ng); Drug: Capsaicin + Flupirtine 0.5 µg; Drug: Capsaicin + Flupirtine 1.2 µg; Drug: Capsaicin + Flupirtine 3.0 µg; Drug: Capsaicin + Flupirtine 7.6 µg; Drug: Placebo (SIF only, no capsaicin or Flupirtine)

Heat Sequence A

EXPERIMENTAL

Participants receive three slow increasingly warm intradermal injections in the following order: 1. Room temperature SIF (control) 2. Heated SIF (placebo) 3. Heated SIF + Flupirtine 124 µg Injections are randomized using a Williams design. Pain is rated every 5 seconds until 6 consecutive zeros.

Drug: Room Temperature Injection (Control); Drug: Heated injection without Flupirtine; Drug: Heated Injection with Flupirtine 124 µg

Heat Sequence B

EXPERIMENTAL

Same injections as Heat Sequence A, administered in a different order according to Williams design.

Drug: Room Temperature Injection (Control); Drug: Heated injection without Flupirtine; Drug: Heated Injection with Flupirtine 124 µg

Heat Sequence C

EXPERIMENTAL

Same injections as Heat Sequence A, administered in a different order according to Williams design.

Drug: Room Temperature Injection (Control); Drug: Heated injection without Flupirtine; Drug: Heated Injection with Flupirtine 124 µg

Heat Sequence D

EXPERIMENTAL

Same injections as Heat Sequence A, administered in a different order according to Williams design.

Drug: Room Temperature Injection (Control); Drug: Heated injection without Flupirtine; Drug: Heated Injection with Flupirtine 124 µg

Heat Sequence E

EXPERIMENTAL

Same injections as Heat Sequence A, administered in a different order according to Williams design.

Drug: Room Temperature Injection (Control); Drug: Heated injection without Flupirtine; Drug: Heated Injection with Flupirtine 124 µg

Heat Sequence F

EXPERIMENTAL

Same injections as Heat Sequence A, administered in a different order according to Williams design.

Drug: Room Temperature Injection (Control); Drug: Heated injection without Flupirtine; Drug: Heated Injection with Flupirtine 124 µg

Interventions

Capsaicin only (7.6 ng) DRUG

Intradermal injection of 7.6 ng capsaicin (0.5 µM, 50 µL) in synthetic interstitial fluid (SIF) without Flupirtine. Used to induce experimental burning pain in the skin.

Capsaicin Sequence A; Capsaicin Sequence B; Capsaicin Sequence C; Capsaicin Sequence D; Capsaicin Sequence E; Capsaicin Sequence F

Capsaicin + Flupirtine 0.5 µg DRUG

Intradermal co-injection of 7.6 ng capsaicin (0.5 µM) and 0.5 µg Flupirtine in 50 µL SIF. Used to assess local analgesic effect of very low-dose Flupirtine on chemically induced pain.

Capsaicin Sequence A; Capsaicin Sequence B; Capsaicin Sequence C; Capsaicin Sequence D; Capsaicin Sequence E; Capsaicin Sequence F

Capsaicin + Flupirtine 1.2 µg DRUG

Intradermal co-injection of 7.6 ng capsaicin and 1.2 µg Flupirtine in 50 µL SIF. Part of dose-response evaluation for peripheral pain inhibition.

Capsaicin Sequence A; Capsaicin Sequence B; Capsaicin Sequence C; Capsaicin Sequence D; Capsaicin Sequence E; Capsaicin Sequence F

Capsaicin + Flupirtine 3.0 µg DRUG

Intradermal co-injection of 7.6 ng capsaicin and 3.0 µg Flupirtine in 50 µL SIF. Intermediate dose in microdose titration series.

Capsaicin Sequence A; Capsaicin Sequence B; Capsaicin Sequence C; Capsaicin Sequence D; Capsaicin Sequence E; Capsaicin Sequence F

Capsaicin + Flupirtine 7.6 µg DRUG

Intradermal co-injection of 7.6 ng capsaicin and 7.6 µg Flupirtine in 50 µL SIF. This is the highest Flupirtine microdose used in the capsaicin model.

Capsaicin Sequence A; Capsaicin Sequence B; Capsaicin Sequence C; Capsaicin Sequence D; Capsaicin Sequence E; Capsaicin Sequence F

Placebo (SIF only, no capsaicin or Flupirtine) DRUG

Intradermal injection of 50 µL synthetic interstitial fluid without capsaicin or Flupirtine. Used as negative control for capsaicin-Flupirtine co-injection conditions.

Capsaicin Sequence A; Capsaicin Sequence B; Capsaicin Sequence C; Capsaicin Sequence D; Capsaicin Sequence E; Capsaicin Sequence F

Room Temperature Injection (Control) DRUG

Intradermal slow infusion of SIF at \~23°C using a programmable pump. No capsaicin or Flupirtine included. Used as baseline control in heat model.

Heat Sequence A; Heat Sequence B; Heat Sequence C; Heat Sequence D; Heat Sequence E; Heat Sequence F

Heated injection without Flupirtine DRUG

Intradermal slow infusion of synthetic interstitial fluid preheated up to \~52°C. No Flupirtine included. Used to induce thermal pain in human skin.

Heat Sequence A; Heat Sequence B; Heat Sequence C; Heat Sequence D; Heat Sequence E; Heat Sequence F

Heated Injection with Flupirtine 124 µg DRUG

Intradermal slow infusion of synthetic interstitial fluid up to \~52°C containing 124 µg Flupirtine. Used to test local analgesic effect of high-dose Flupirtine in heat pain model.

Heat Sequence A; Heat Sequence B; Heat Sequence C; Heat Sequence D; Heat Sequence E; Heat Sequence F

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Stefan Heber: lead

Study Sites (1)

Medical University of Vienna

Vienna, Austria, 1090, Austria

Location

Related Publications (3)

• Heber S, Resch F, Ciotu CI, Gleiss A, Heber UM, Macher-Beer A, Bhuiyan S, Gold-Binder M, Kain R, Sator S, Fischer MJM. Human heat sensation: A randomized crossover trial. Sci Adv. 2024 Sep 6;10(36):eado3498. doi: 10.1126/sciadv.ado3498. Epub 2024 Sep 4.

  PMID: 39231217 BACKGROUND

• Heber S, Gold-Binder M, Ciotu CI, Witek M, Ninidze N, Kress HG, Fischer MJM. A Human TRPA1-Specific Pain Model. J Neurosci. 2019 May 15;39(20):3845-3855. doi: 10.1523/JNEUROSCI.3048-18.2019. Epub 2019 Mar 12.

  PMID: 30862667 BACKGROUND

• Heber S, Ciotu CI, Hartner G, Gold-Binder M, Ninidze N, Gleiss A, Kress HG, Fischer MJM. TRPV1 antagonist BCTC inhibits pH 6.0-induced pain in human skin. Pain. 2020 Jul;161(7):1532-1541. doi: 10.1097/j.pain.0000000000001848.

  PMID: 32107360 BACKGROUND

MeSH Terms

Conditions

Pain

Interventions

Capsaicin; flupirtine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Polyunsaturated Alkamides; Amides; Organic Chemicals; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Model Details: This study uses a randomized, placebo-controlled, single-visit crossover design in healthy volunteers. Each participant receives multiple intradermal injections in a predefined sequence, with each injection acting as its own control. A balanced Williams design ensures equal distribution of intervention order. The interventions include capsaicin with or without Flupirtine (multiple doses) and heated fluid injections with or without Flupirtine. Pain intensity is measured every 5 seconds using numeric rating scales. The model is optimized for within-subject comparisons of localized, short-duration nociceptive responses and permits precise analysis of peripheral analgesic effects without systemic drug exposure.

Study Record Dates

• First Submitted: May 3, 2025
• First Posted: May 14, 2025
• Study Start: May 8, 2025
• Primary Completion: May 28, 2025
• Study Completion: May 28, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: IPD will be made available at the time of publication of the primary results article, as a supplementary file.
• Access Criteria: All individuals who have access to the published article will be able to access the individual participant data (IPD) and supporting information as supplementary material. No special request or data use agreement is required.

Locations

AU (1)