Mechanisms of Human Heat Perception - Involvement of TRPA1, TRPV1 and TRPM3

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-13

Study Completion Date

2022-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Mechanism of Human Cold Pain Perception - Involvement of TRPA1, TRPM8, Nav1.7 and Nav1.8

NCT05935280

Pain

COMPLETED EARLY_PHASE1

Hyperthermia in Patients With Chronic Primary Pain - Effects on Thermoregulation, Somatosensory System and Movement Evoked Pain

NCT07101978

Hyperthermia Chronic Primary Pain Widespread Pain +10 more

NOT_YET_RECRUITING NA

Pain Sensitivity During Puberty

NCT05145595

Pain

COMPLETED NA

Neural and Psychological Mechanisms of Pain Perception

NCT02446262

Pain Normal Physiology Healthy Volunteers

RECRUITING NA

Intra- and Inter-individual Differences of Pain

NCT05616091

Experimental Pain in Healthy Human Subjects

COMPLETED NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Pain

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

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

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Hot injection without TRP-channel inhibition

Pain induced by an increasingly hot intradermal injection up to 52°C over 2 minutes.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

No pharmacological intervention

Hot injection with TRPA1-inhibition

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.

Group Type EXPERIMENTAL

TRPA1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPV1-inhibition

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.

Group Type EXPERIMENTAL

TRPV1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPM3-inhibition

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.

Group Type EXPERIMENTAL

TRPM3-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPA1- and TRPV1-inhibition

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.

Group Type EXPERIMENTAL

TRPA1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid

TRPV1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPA1- and TRPM3-inhibition

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.

Group Type EXPERIMENTAL

TRPA1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid

TRPM3-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPM3- and TRPV1-inhibition

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.

Group Type EXPERIMENTAL

TRPV1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid

TRPM3-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPA1-, TRPV1 and TRPM3-inhibition

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.

Group Type EXPERIMENTAL

TRPA1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid

TRPV1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid

TRPM3-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPA1-, TRPM3- and chloride channel inhibition

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.

Group Type EXPERIMENTAL

TRPA1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid

TRPM3-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid

Chloride-channel inhibitor

Intervention Type DRUG

Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPV1-, TRPM3- and chloride channel inhibition

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.

Group Type EXPERIMENTAL

TRPV1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid

TRPM3-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid

Chloride-channel inhibitor

Intervention Type DRUG

Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPA1- and chloride channel inhibition

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.

Group Type EXPERIMENTAL

TRPA1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid

Chloride-channel inhibitor

Intervention Type DRUG

Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPV1- and chloride channel inhibition

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.

Group Type EXPERIMENTAL

TRPV1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid

Chloride-channel inhibitor

Intervention Type DRUG

Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPV1-, TRPA1, TRPM3- and chloride channel inhibition

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.

Group Type EXPERIMENTAL

TRPA1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid

TRPV1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid

TRPM3-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid

Chloride-channel inhibitor

Intervention Type DRUG

Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPM3- and chloride channel inhibition

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.

Group Type EXPERIMENTAL

TRPM3-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid

Chloride-channel inhibitor

Intervention Type DRUG

Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Hot injection with TRPV1-, TRPA1, and chloride channel inhibition

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.

Group Type EXPERIMENTAL

TRPA1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid

TRPV1-inhibitor

Intervention Type DRUG

Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid

Chloride-channel inhibitor

Intervention Type DRUG

Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Hot injection with chloride channel inhibition

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.

Group Type EXPERIMENTAL

Chloride-channel inhibitor

Intervention Type DRUG

Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

TRPA1-inhibitor

Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid

Intervention Type DRUG

TRPV1-inhibitor

Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid

Intervention Type DRUG

TRPM3-inhibitor

Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid

Intervention Type DRUG

Placebo

No pharmacological intervention

Intervention Type DRUG

Chloride-channel inhibitor

Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Specific antagonist of the TRPA1 channel Specific antagonist of the TRPV1 channel Specific antagonist of the TRPM3 channel No antagonist Specific inhibitor of a chloride channel

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.

Exclusion Criteria

* 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)

Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes