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

Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05275751
• Other study ID #: EK Nr: 1152/2020
• Status: Completed
• Phase: Early Phase 1
• Start date: June 13, 2022
• Est. completion date: November 30, 2022

Study information

• Verified date: March 2023
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: November 30, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• TRPA1-inhibitor
Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid
• TRPV1-inhibitor
Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid
• TRPM3-inhibitor
Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid
• Placebo
No pharmacological intervention
• Chloride-channel inhibitor
Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Through study completion, on average 4 days.
Secondary	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)	Through study completion, on average 4 days.