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

Pain Clinical Trial

Official title:

Human Cold Pain - a Single-group, Randomized, Placebo-controlled, Adaptive, Factorial Crossover Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05935280
• Other study ID #: EK Nr: 1164/2023
• Status: Completed
• Phase: Early Phase 1
• Start date: July 7, 2023
• Est. completion date: September 1, 2023

Study information

• Verified date: March 2024
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Animal studies suggest that the transient receptor potential ion channels TRPM8 and TRPA1 are cold sensors and that sodium channels Nav1.8 and Nav1.7 are essential for detecting pain induced by cold temperatures. This study aims to validate these findings in humans.

Description:

It is essential for human survival to be able to perceive potentially harmful cold. The perception of slight cooling in animals depends on the ion channel TRPM8, but this may represent a largely separate mechanism from painful cold. In mice, TRPM8 and TRPA1 appear to be involved, but also the sodium channels Nav1.7 and Nav1.8, through their temperature-dependent function. These receptors might be redundant, so that failure of individual receptors only leads to no or only a partial reduction in the detection of cold.

Since results obtained in animals do not always translate to humans, the investigators want to clarify whether TRPM8, TRPA1, Nav1.7 and Nav1.8 are involved in the perception of cold pain in humans.

In order to induce cold pain experimentally, an increasingly cooled solution (down to 3°C) is injected into the skin, and the inhibitors for the mentioned targets are added individually and in combination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: September 1, 2023
• Est. primary completion date: September 1, 2023
• 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

• Sensory deficit, skin disease or hematoma of unknown origin in physical examination of the test site

Related Conditions & MeSH terms

• Pain

Intervention

Other:
• Room temperature
Room temperature injection
• Cold temperature
Cold temperature injection

Drug:
• Lidocain
Unspecific sodium channel blocker
• PF-05105679
Specific antagonist of the TRPM8 ion channel
• A967079
Specific antagonist of the TRPA1 ion channel
• PF-05089771
Specific antagonist of the Nav1.7 sodium channel
• PF-06305591
Specific antagonist of the Nav1.8 sodium channel

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	AUC Pain3°C	The primary outcome variable is the area under the curve (AUC) of pain ratings over a limited duration of the infusion period, i.e. from 120-150 seconds (last 30 seconds of the cold stimulus).	Through study completion, on average 90 minutes.
Secondary	AUC Pain	The secondary outcome variable is the area under the curve (AUC) of pain ratings over the full duration of the infusion period (full 150 seconds of the cold stimulus).	Through study completion, on average 90 minutes.