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Completed

NCT Number: NCT05275751

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

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.

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Key information

Conditions

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

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Medical University of Vienna

Vienna, 1090, Austria

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

TRPA1-inhibitor

Drug

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

Other names: Specific antagonist of the TRPA1 channel

TRPV1-inhibitor

Drug

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

Other names: Specific antagonist of the TRPV1 channel

TRPM3-inhibitor

Drug

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

Other names: Specific antagonist of the TRPM3 channel

Placebo

Drug

No pharmacological intervention

Other names: No antagonist

Chloride-channel inhibitor

Drug

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

Other names: Specific inhibitor of a chloride channel

Primary outcomes

  1. 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)

Secondary outcomes

  1. HPI - Heat pain inhibition

    Time frame: Through study completion, on average 4 days.

    '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)

Sponsors and collaborators

Lead sponsor

Medical University of Vienna

Other

Registry information

Official study title

Human Heat Sensation - a Single-group, Randomized, Placebo-controlled, Adaptive, Full-factorial Crossover Trial

Important dates

Study start
2022
Primary completion
2022
Study completion
2022
First posted
Mar 11, 2022
Registry last updated
Mar 17, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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