L-menthol as a Topical Counter-irritant to TRPA1-induced Neurogenic Inflammation and Pain

January 11, 2016 updated by: Parisa Gazerani, Aalborg University

High-concentration L-menthol as a Counter-irritant to TRPA1-induced Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde

The aim of this study is to quantitatively characterize the effects of L-menthol as a topical counter-irritant on cutaneous pain and hyperalgesia provoked by topical application of the TRPA1-agonist trans-cinnamaldehyde (CA) in healthy human volunteers.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is designed as an experimental model in healthy humans.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 18 healthy men and women aged 18-50 years willing to abstain from alcohol, nicotine, caffeine and pain medication 24 hours before experimental sessions

Exclusion Criteria:

  • Pregnancy
  • Skin disorders (e.g. contact eczema)
  • Chronic pain conditions
  • Drug addiction defined as the use of cannabis, opioids or other drugs
  • Previous neurologic, musculoskeletal or mental illnesses
  • Lack of ability to cooperate

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Vehicle, topical ethanol 96%
Exposure: 10 % topical trans-cinnamaldehyde [CAS Number: 14371-10-9] Vehicle: 96% ethanol
Other: Vehicle, topical ethanol 96%
Organic solvent CAS Number: 64-17-5
Experimental: Topical L-menthol 40%
Exposure: 10 % trans-cinnamaldehyde [CAS Number: 14371-10-9] Intervention: 40% l-menthol [CAS Number: 2216-51-5] Vehicle: 96% ethanol
Other: Topical L-menthol 40%
Naturally occurring local anaesthetic, counterirritant and TPRM8-agonist. CAS Number: 2216-51-5
Other Names:
  • Menthol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Spontaneous pain intensity [self-reported on a visual analog scale]
Time Frame: 0-20 minutes with a sampling frequency of 1/1 min
Rating of the overall pain intensity on a visual analog scale (VAS ranging from "No pain" = 0, to "worst imaginable pain" =10) once every minute
0-20 minutes with a sampling frequency of 1/1 min

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Neurogenic inflammation [Measured by Laser speckle flowmetry in a 3x3 cm area]
Time Frame: 20-25 minutes post induction
Speckle contrast flowmetry (MoorFLPI, Moor Instruments, Devon, UK). The assessment is conducted with a 30-cm distance between the head of the laser and the application area with an exposure time of 8.3ms. Single frame images are analyzed on appertaining software (MoorFLPI Review V 4.0, Moor Instruments), upon which the arithmetic mean flux (arbitrary units) is calculated. The longitudinal analysis of the spatial dispersion of neurogenic inflammation is performed using the line histogram tool. A 7-cm line centered in the area of application was placed longitudinally along the volar forearm and the perfusion intensity is recorded every 2.5 mm.
20-25 minutes post induction
Heat hyperalgesia
Time Frame: 25-27.5 minutes post induction
Heat pain threshold assessments is performed with a Medoc Pathway (Medoc Ltd, Ramat Yishay, Israel) equipped with a 3 × 3 cm advanced thermal stimulator probe where the baseline temperature was set to 32 °C. Ramp stimuli of 1 °C/s are delivered and the subjects are asked to identify the heat pain threshold upon which the temperature is returned to the baseline at a rate of 5 °C/s. The test result is calculated as the arithmetic mean of the outcome from three repeated stimuli. Heat hyperalgesia is considered to be a significant drop in heat pain threshold
25-27.5 minutes post induction
Mechanical hyperalgesia
Time Frame: 27.5-30 minutes post induction
To evaluate the mechanical pain threshold (MPT) an electronic von Frey transducer and an electronic coVAS connected to a SENSE-Box setup is used (both items: Somedic, Hörby, Sweden). Five ramp stimuli from 0-110 g at a rate of 5g/1 sec with the default stimulus probe is conducted at different locations within the application area. The subjects are instructed to continuously rate the perceived pain on the coVAS ranging from "No pain" (0) to "worst imaginable pain" (10). The arithmetic mean of the VAS scores yields three MPTs (fixed to VAS = 0.5, 1 and 2) and an area-under-the-curve (AUC).
27.5-30 minutes post induction

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Aalborg University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 8, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 12, 2016

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 12, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • N-20130005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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