PainEarly Phase 1NCT05275751
Mechanisms of Human Heat Perception - Involvement of TRPA1, TRPV1 and TRPM3
A Early Phase 1 study testing TRPA1-inhibitor, TRPV1-inhibitor and TRPM3-inhibitor in people with Pain, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Animal studies suggest that the ion channels TRPV1, TRPA1 and TRPM3 are the relevant heat sensors. This study aims to validate these findings in humans. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain
- What is being tested?
- TRPA1-inhibitor, TRPV1-inhibitor and TRPM3-inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 1 siteAustria
- Study dates
- 13 Jun 2022to 30 Nov 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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, known allergic reactions to citrus fruits (but excluding food intolerances).
- Sensory deficit, skin disease or hematoma of unknown origin in physical examination of the test site
- Symptoms of a respiratory tract infection (Covid-19 related criterion)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Human Heat Sensation - a Single-group, Randomized, Placebo-controlled, Adaptive, Full-factorial Crossover Trial
Animal studies suggest that the ion channels TRPV1, TRPA1 and TRPM3 are the relevant heat sensors. This study aims to validate these findings in humans.
Read the detailed description
Surprisingly, it is still not fully understood how humans perceive heat pain. There are several heat-sensitive ion channels whose manipulation in animals resulted in a more or less pronounced phenotype. However, complete blockade of heat sensation in animals has only recently been achieved. In triple knockout mice lacking TRPA1, TRPV1 and TRPM3, it was recently shown that only in the absence of all three receptors heat perception is largely abolished. Although the authors were unable to elucidate the underlying mechanism of this redundancy, the redundancy appears to have evolutionary value for protection against burns. In addition, recent evidence suggests that TRPV1 plays a role as a first-line defense against heat injury, i.e., that it encodes noninjurious heat injury in humans.
The goal of this study is to test whether the redundant functions of TRPV1, TRPA1 and TRPM3 observed in mice with respect to heat perception also apply to humans. More broadly, we want to understand which receptors enable humans to perceive heat pain. The study also aims to test if a chloride channel is involved in heat perception.
Design: Cross-over study with a Williams design group, 16 treatments incl. a placebo control.
- Conditions
- Pain
- Being tested
- TRPA1-inhibitor, TRPV1-inhibitor, TRPM3-inhibitor, Placebo, Chloride-channel inhibitor
- Keywords
- Psychophysics, Human physiology, Sensory neuron, TRP channels, Heat perception
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TRPA1-inhibitorDrug
Also called Specific antagonist of the TRPA1 channel
Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid
TRPV1-inhibitorDrug
Also called Specific antagonist of the TRPV1 channel
Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid
TRPM3-inhibitorDrug
Also called Specific antagonist of the TRPM3 channel
Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid
PlaceboDrug
Also called No antagonist
No pharmacological intervention
Chloride-channel inhibitorDrug
Also called Specific inhibitor of a chloride channel
Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid
| Study group | Role | What they receive |
|---|---|---|
| Hot injection without TRP-channel inhibition | Placebo comparator | Pain induced by an increasingly hot intradermal injection up to 52°C over 2 minutes. Receives: Drug: Placebo |
| Hot injection with TRPA1-inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1 is blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPA1-inhibitor |
| Hot injection with TRPV1-inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPV1 is blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPV1-inhibitor |
| Hot injection with TRPM3-inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPM3 is blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPM3-inhibitor |
| Hot injection with TRPA1- and TRPV1-inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1 and TRPV1 are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPA1-inhibitor; Drug: TRPV1-inhibitor |
| Hot injection with TRPA1- and TRPM3-inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1 and TRPM3 are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPA1-inhibitor; Drug: TRPM3-inhibitor |
| Hot injection with TRPM3- and TRPV1-inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPM3 and TRPV1 are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPV1-inhibitor; Drug: TRPM3-inhibitor |
| Hot injection with TRPA1-, TRPV1 and TRPM3-inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1, TRPV1 and TRPM3 are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPA1-inhibitor; Drug: TRPV1-inhibitor; Drug: TRPM3-inhibitor |
| Hot injection with TRPA1-, TRPM3- and chloride channel inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1, TRPM3 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPA1-inhibitor; Drug: TRPM3-inhibitor; Drug: Chloride-channel inhibitor |
| Hot injection with TRPV1-, TRPM3- and chloride channel inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPV1, TRPM3 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPV1-inhibitor; Drug: TRPM3-inhibitor; Drug: Chloride-channel inhibitor |
| Hot injection with TRPA1- and chloride channel inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPA1-inhibitor; Drug: Chloride-channel inhibitor |
| Hot injection with TRPV1- and chloride channel inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPV1 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPV1-inhibitor; Drug: Chloride-channel inhibitor |
| Hot injection with TRPV1-, TRPA1, TRPM3- and chloride channel inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPV1, TRPA1, TRPM3 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPA1-inhibitor; Drug: TRPV1-inhibitor; Drug: TRPM3-inhibitor; Drug: Chloride-channel inhibitor |
| Hot injection with TRPM3- and chloride channel inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPM3 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPM3-inhibitor; Drug: Chloride-channel inhibitor |
| Hot injection with TRPV1-, TRPA1, and chloride channel inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPV1, TRPA1, and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: TRPA1-inhibitor; Drug: TRPV1-inhibitor; Drug: Chloride-channel inhibitor |
| Hot injection with chloride channel inhibition | Experimental | Pain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while a chloride channel is blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. Receives: Drug: Chloride-channel inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
HPI(50-52) - Heat pain inhibition in the range between 50°C and 52°C
'Heat pain inhibition between 50 and 52 °C', abbreviated HPI(50-52). A value of 0% would indicate that for a given injection there was no inhibition between 50 and 52 °C, i.e. that the injection was equal to a heated control injection without substance. In contrast, a value of 100% would indicate that there was complete inhibition and the injection was as indistinguishable from the injection at room temperature.
Of note, pain is rated during the application of the test substances. There are 2 experimental days with injections, separated by a few days, resulting in a time frame of 4 days on average.
The principle of AUC calculations from pain ratings during injections is described in Heber et al. 2020 (PMID: 32107360 DOI: 0.1097/j.pain.0000000000001848)
Measured: Through study completion, on average 4 days.
Secondary outcomes (1)
HPI - Heat pain inhibition
'Heat pain inhibition between room temperature and 52 °C', abbreviated HPI. A value of 0% would indicate that for a given injection there was no inhibition, i.e. that the injection was equal to a heated control injection without substance. In contrast, a value of 100% would indicate that there was complete inhibition and the injection was as indistinguishable from the injection at room temperature.
Of note, pain is rated during the application of the test substances. There are 2 experimental days with injections, separated by a few days, resulting in a time frame of 4 days on average.
The principle of AUC calculations from pain ratings during injections is described in Heber et al. 2020 (PMID: 32107360 DOI: 0.1097/j.pain.0000000000001848)
Measured: Through study completion, on average 4 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2022
- Study start13 Jun 2022
- Primary completion30 Nov 2022
- Study completion30 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- Factorial: There are 4 treatments (TRPV1-, TRPA1-, TRPM3- and chloride channel inhibition). These will be applied in all possible combinations (16). Each healthy volunteer will receive 8 of these 16 combinations in a sequence defined by a Williams square (Hinkelmann, K., and Kempthorne, O. (2005). Design and Analysis of Experiments Vol. 2 - Advanced Experimental Design (Wiley)) Randomized: Volunteers will be randomly assigned to a pre-specified sequence. Placebo-controlled: One of the 16 combinations includes none of the three treatments, i.e., can be regarded as placebo control. Adaptive: Due to the complex study design, a priori assumptions about the distribution and correlation of data could not be made reliably. Therefore, after 16 volunteers, the responsible bio-statistician will simulate how much more patients are necessary to detect the a priori defined effect size with the until then observed data
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stefan Heber, Medical University of Vienna
- Investigators
- Michael JM Fischer, Professor MD, Study chair, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05275751
- Sponsor's protocol ID
- EK Nr: 1152/2020
- Status last verified
- Mar 2023
- First submitted
- 22 Feb 2022
- Last updated
- 17 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All raw data will be shared with other researches upon reasonable request
Publications
Chubanov V, Grimm C, Hill K, Schaefer M, Kottgen M, Storch U, Mederos Y Schnitzler M, Kudrina V, Erbacher A, Gudermann T. Physiological functions and pharmacological targeting of transient receptor potential channels. Pharmacol Rev. 2025 Nov;77(6):100089. doi: 10.1016/j.pharmr.2025.100089. Epub 2025 Sep 13.
PubMed 41118703
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Heat Sensation - a Single-group, Randomized, Placebo-controlled, Adaptive, Full-factorial Crossover Trial
- ClinicalTrials.gov ID
- NCT05275751
- Acronym / sponsor ID
- EK Nr: 1152/2020
- Conditions
- Pain
- Keywords
- Psychophysics, Human physiology, Sensory neuron, TRP channels, Heat perception
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- 13 Jun 2022 (actual)
- Primary completion
- 30 Nov 2022 (actual)
- Study completion
- 30 Nov 2022 (actual)
- First posted
- 11 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Animal studies suggest that the ion channels TRPV1, TRPA1 and TRPM3 are the relevant heat sensors. This study aims to validate these findings in humans.
Detailed description
Surprisingly, it is still not fully understood how humans perceive heat pain. There are several heat-sensitive ion channels whose manipulation in animals resulted in a more or less pronounced phenotype. However, complete blockade of heat sensation in animals has only recently been achieved. In triple knockout mice lacking TRPA1, TRPV1 and TRPM3, it was recently shown that only in the absence of all three receptors heat perception is largely abolished. Although the authors were unable to elucidate the underlying mechanism of this redundancy, the redundancy appears to have evolutionary value for protection against burns. In addition, recent evidence suggests that TRPV1 plays a role as a first-line defense against heat injury, i.e., that it encodes noninjurious heat injury in humans.
The goal of this study is to test whether the redundant functions of TRPV1, TRPA1 and TRPM3 observed in mice with respect to heat perception also apply to humans. More broadly, we want to understand which receptors enable humans to perceive heat pain. The study also aims to test if a chloride channel is involved in heat perception.
Design: Cross-over study with a Williams design group, 16 treatments incl. a placebo control.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 16
- Model description
- Factorial: There are 4 treatments (TRPV1-, TRPA1-, TRPM3- and chloride channel inhibition). These will be applied in all possible combinations (16). Each healthy volunteer will receive 8 of these 16 combinations in a sequence defined by a Williams square (Hinkelmann, K., and Kempthorne, O. (2005). Design and Analysis of Experiments Vol. 2 - Advanced Experimental Design (Wiley)) Randomized: Volunteers will be randomly assigned to a pre-specified sequence. Placebo-controlled: One of the 16 combinations includes none of the three treatments, i.e., can be regarded as placebo control. Adaptive: Due to the complex study design, a priori assumptions about the distribution and correlation of data could not be made reliably. Therefore, after 16 volunteers, the responsible bio-statistician will simulate how much more patients are necessary to detect the a priori defined effect size with the until then observed data
| Arm | Type | Receives |
|---|---|---|
| Hot injection without TRP-channel inhibition | Placebo comparator | Drug: PlaceboPain induced by an increasingly hot intradermal injection up to 52°C over 2 minutes. |
| Hot injection with TRPA1-inhibition | Experimental | Drug: TRPA1-inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1 is blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPV1-inhibition | Experimental | Drug: TRPV1-inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPV1 is blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPM3-inhibition | Experimental | Drug: TRPM3-inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPM3 is blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPA1- and TRPV1-inhibition | Experimental | Drug: TRPA1-inhibitor, Drug: TRPV1-inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1 and TRPV1 are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPA1- and TRPM3-inhibition | Experimental | Drug: TRPA1-inhibitor, Drug: TRPM3-inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1 and TRPM3 are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPM3- and TRPV1-inhibition | Experimental | Drug: TRPV1-inhibitor, Drug: TRPM3-inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPM3 and TRPV1 are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPA1-, TRPV1 and TRPM3-inhibition | Experimental | Drug: TRPA1-inhibitor, Drug: TRPV1-inhibitor, Drug: TRPM3-inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1, TRPV1 and TRPM3 are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPA1-, TRPM3- and chloride channel inhibition | Experimental | Drug: TRPA1-inhibitor, Drug: TRPM3-inhibitor, Drug: Chloride-channel inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1, TRPM3 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPV1-, TRPM3- and chloride channel inhibition | Experimental | Drug: TRPV1-inhibitor, Drug: TRPM3-inhibitor, Drug: Chloride-channel inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPV1, TRPM3 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPA1- and chloride channel inhibition | Experimental | Drug: TRPA1-inhibitor, Drug: Chloride-channel inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPA1 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPV1- and chloride channel inhibition | Experimental | Drug: TRPV1-inhibitor, Drug: Chloride-channel inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPV1 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPV1-, TRPA1, TRPM3- and chloride channel inhibition | Experimental | Drug: TRPA1-inhibitor, Drug: TRPV1-inhibitor, Drug: TRPM3-inhibitor, Drug: Chloride-channel inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPV1, TRPA1, TRPM3 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPM3- and chloride channel inhibition | Experimental | Drug: TRPM3-inhibitor, Drug: Chloride-channel inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPM3 and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with TRPV1-, TRPA1, and chloride channel inhibition | Experimental | Drug: TRPA1-inhibitor, Drug: TRPV1-inhibitor, Drug: Chloride-channel inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while TRPV1, TRPA1, and a chloride channel are blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
| Hot injection with chloride channel inhibition | Experimental | Drug: Chloride-channel inhibitorPain is induced by an increasingly hot intradermal injection up to 52°C over 2 minutes, while a chloride channel is blocked pharmacologically by an antagonist dissolved in the hot fluid (synthetic interstitial fluid). The antagonist(s) have sufficient concentration to reliably block the channel. The total dose is in the range of a microdose trial. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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, known allergic reactions to citrus fruits (but excluding food intolerances).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TRPA1-inhibitorAlso: Specific antagonist of the TRPA1 channelPharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid | Drug | Hot injection with TRPA1- and TRPM3-inhibition, Hot injection with TRPA1- and TRPV1-inhibition, Hot injection with TRPA1- and chloride channel inhibition, Hot injection with TRPA1-, TRPM3- and chloride channel inhibition, Hot injection with TRPA1-, TRPV1 and TRPM3-inhibition, Hot injection with TRPA1-inhibition, Hot injection with TRPV1-, TRPA1, TRPM3- and chloride channel inhibition, Hot injection with TRPV1-, TRPA1, and chloride channel inhibition |
| TRPV1-inhibitorAlso: Specific antagonist of the TRPV1 channelPharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid | Drug | Hot injection with TRPA1- and TRPV1-inhibition, Hot injection with TRPA1-, TRPV1 and TRPM3-inhibition, Hot injection with TRPM3- and TRPV1-inhibition, Hot injection with TRPV1- and chloride channel inhibition, Hot injection with TRPV1-, TRPA1, TRPM3- and chloride channel inhibition, Hot injection with TRPV1-, TRPA1, and chloride channel inhibition, Hot injection with TRPV1-, TRPM3- and chloride channel inhibition, Hot injection with TRPV1-inhibition |
| TRPM3-inhibitorAlso: Specific antagonist of the TRPM3 channelPharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid | Drug | Hot injection with TRPA1- and TRPM3-inhibition, Hot injection with TRPA1-, TRPM3- and chloride channel inhibition, Hot injection with TRPA1-, TRPV1 and TRPM3-inhibition, Hot injection with TRPM3- and TRPV1-inhibition, Hot injection with TRPM3- and chloride channel inhibition, Hot injection with TRPM3-inhibition, Hot injection with TRPV1-, TRPA1, TRPM3- and chloride channel inhibition, Hot injection with TRPV1-, TRPM3- and chloride channel inhibition |
| PlaceboAlso: No antagonistNo pharmacological intervention | Drug | Hot injection without TRP-channel inhibition |
| Chloride-channel inhibitorAlso: Specific inhibitor of a chloride channelPharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid | Drug | Hot injection with TRPA1- and chloride channel inhibition, Hot injection with TRPA1-, TRPM3- and chloride channel inhibition, Hot injection with TRPM3- and chloride channel inhibition, Hot injection with TRPV1- and chloride channel inhibition, Hot injection with TRPV1-, TRPA1, TRPM3- and chloride channel inhibition, Hot injection with TRPV1-, TRPA1, and chloride channel inhibition, Hot injection with TRPV1-, TRPM3- and chloride channel inhibition, Hot injection with chloride channel inhibition |
Primary outcome
HPI(50-52) - Heat pain inhibition in the range between 50°C and 52°C
Time frame: Through study completion, on average 4 days.
'Heat pain inhibition between 50 and 52 °C', abbreviated HPI(50-52). A value of 0% would indicate that for a given injection there was no inhibition between 50 and 52 °C, i.e. that the injection was equal to a heated control injection without substance. In contrast, a value of 100% would indicate that there was complete inhibition and the injection was as indistinguishable from the injection at room temperature. Of note, pain is rated during the application of the test substances. There are 2 experimental days with injections, separated by a few days, resulting in a time frame of 4 days on average. The principle of AUC calculations from pain ratings during injections is described in Heber et al. 2020 (PMID: 32107360 DOI: 0.1097/j.pain.0000000000001848)
1 secondary outcome
HPI - Heat pain inhibition
Time frame: Through study completion, on average 4 days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2023.
- Derived from this study: PubMed 41118703Chubanov V, Grimm C, Hill K, Schaefer M, Kottgen M, Storch U, Mederos Y Schnitzler M, Kudrina V, Erbacher A, Gudermann T. Physiological functions and pharmacological targeting of transient receptor potential channels. Pharmacol Rev. 2025 Nov;77(6):100089. doi: 10.1016/j.pharmr.2025.100089. Epub 2025 Sep 13.
- Individual participant dataSharing planned: Yes. All raw data will be shared with other researches upon reasonable request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael JM Fischer, Professor MD study chair
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing TRPA1-inhibitor, TRPV1-inhibitor and TRPM3-inhibitor in people with Pain, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HPI(50-52) - Heat pain inhibition in the range between 50°C and 52°C (time frame: Through study completion, on average 4 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05275751, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2023.