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InflammationNCT02653703

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

A study testing Topical L-menthol 40% in people with Inflammation and Pruritus, run by Aalborg University.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Inflammation, Pruritus, Hyperalgesia
What is being tested?
Topical L-menthol 40%
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
14 participants
Where
No sites listed yet
Study dates
Oct 2014to Dec 2014
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • Healthy volunteers accepted
  • Adult

Who may be able to join

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

Who cannot join

  • 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

About this study

Official title: 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.

Read the detailed description

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

Being tested
Topical L-menthol 40%, Vehicle, topical ethanol 96%
Medical subject headings
Inflammation, Pruritus, Hyperalgesia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Topical L-menthol 40%Other

    Also called Menthol

    Naturally occurring local anaesthetic, counterirritant and TPRM8-agonist. CAS Number: 2216-51-5

  • Vehicle, topical ethanol 96%Other

    Organic solvent CAS Number: 64-17-5

Study groups in NCT02653703
Study groupRoleWhat they receive
Vehicle, topical ethanol 96%Placebo comparatorExposure: 10 % topical trans-cinnamaldehyde [CAS Number: 14371-10-9] Vehicle: 96% ethanol
Receives: Other: Vehicle, topical ethanol 96%
Topical L-menthol 40%ExperimentalExposure: 10 % trans-cinnamaldehyde [CAS Number: 14371-10-9] Intervention: 40% l-menthol [CAS Number: 2216-51-5] Vehicle: 96% ethanol
Receives: Other: Topical L-menthol 40%

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Spontaneous pain intensity [self-reported on a visual analog scale]

    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

    Measured: 0-20 minutes with a sampling frequency of 1/1 min

Secondary outcomes (3)

  1. Neurogenic inflammation [Measured by Laser speckle flowmetry in a 3x3 cm area]

    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.

    Measured: 20-25 minutes post induction

  2. Heat hyperalgesia

    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

    Measured: 25-27.5 minutes post induction

  3. Mechanical hyperalgesia

    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).

    Measured: 27.5-30 minutes post induction

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2016 (estimated)
  2. Study startOct 2014
  3. Primary completionDec 2014
  4. Study completionDec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02653703
Sponsor's protocol ID
N-20130005
Status last verified
Jan 2016
First submitted
8 Jan 2016
Last updated
12 Jan 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • Olsen RV, Andersen HH, Moller HG, Eskelund PW, Arendt-Nielsen L. Somatosensory and vasomotor manifestations of individual and combined stimulation of TRPM8 and TRPA1 using topical L-menthol and trans-cinnamaldehyde in healthy volunteers. Eur J Pain. 2014 Oct;18(9):1333-42. doi: 10.1002/j.1532-2149.2014.494.x. Epub 2014 Mar 25.

    PubMed 24664788

  • Hojland CR, Andersen HH, Poulsen JN, Arendt-Nielsen L, Gazerani P. A human surrogate model of itch utilizing the TRPA1 agonist trans-cinnamaldehyde. Acta Derm Venereol. 2015 Sep;95(7):798-803. doi: 10.2340/00015555-2103.

    PubMed 25792226

  • Namer B, Seifert F, Handwerker HO, Maihofner C. TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol. Neuroreport. 2005 Jun 21;16(9):955-9. doi: 10.1097/00001756-200506210-00015.

    PubMed 15931068

  • Namer B, Kleggetveit IP, Handwerker H, Schmelz M, Jorum E. Role of TRPM8 and TRPA1 for cold allodynia in patients with cold injury. Pain. 2008 Sep 30;139(1):63-72. doi: 10.1016/j.pain.2008.03.007. Epub 2008 Apr 25.

    PubMed 18440147

  • Andersen HH, Olsen RV, Moller HG, Eskelund PW, Gazerani P, Arendt-Nielsen L. A review of topical high-concentration L-menthol as a translational model of cold allodynia and hyperalgesia. Eur J Pain. 2014 Mar;18(3):315-25. doi: 10.1002/j.1532-2149.2013.00380.x. Epub 2013 Aug 20.

    PubMed 23963768

  • Leslie TA, Greaves MW, Yosipovitch G. Current topical and systemic therapies for itch. Handb Exp Pharmacol. 2015;226:337-56. doi: 10.1007/978-3-662-44605-8_18.

    PubMed 25861788

  • Heyneman CA. Topical nonsteroidal antiinflammatory drugs for acute soft tissue injuries. Ann Pharmacother. 1995 Jul-Aug;29(7-8):780-2. doi: 10.1177/106002809502907-822.

    PubMed 8520097

  • Andersen HH, Gazerani P, Arendt-Nielsen L. High-Concentration L-Menthol Exhibits Counter-Irritancy to Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde. J Pain. 2016 Aug;17(8):919-29. doi: 10.1016/j.jpain.2016.05.004. Epub 2016 May 31.

    PubMed 27260636

Questions about this trial

What is this clinical trial studying?

A study testing Topical L-menthol 40% in people with Inflammation and Pruritus, run by Aalborg University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Spontaneous pain intensity [self-reported on a visual analog scale] (time frame: 0-20 minutes with a sampling frequency of 1/1 min). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02653703, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2016.

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