Ignite Creation Date:
2025-12-24 @ 7:47 PM
Ignite Modification Date:
2026-02-01 @ 4:54 PM
Study NCT ID:
NCT02653703
Status:
COMPLETED
Last Update Posted:
2016-01-12
First Post:
2016-01-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
L-menthol as a Topical Counter-irritant to TRPA1-induced Neurogenic Inflammation and Pain
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D011537', 'term': 'Pruritus'}, {'id': 'D006930', 'term': 'Hyperalgesia'}], 'ancestors': [{'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D012877', 'term': 'Skin Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D020886', 'term': 'Somatosensory Disorders'}, {'id': 'D012678', 'term': 'Sensation Disorders'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008610', 'term': 'Menthol'}], 'ancestors': [{'id': 'D003511', 'term': 'Cyclohexanols'}, {'id': 'D000441', 'term': 'Hexanols'}, {'id': 'D005233', 'term': 'Fatty Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000081005', 'term': 'Cyclohexane Monoterpenes'}, {'id': 'D003510', 'term': 'Cyclohexanes'}, {'id': 'D003516', 'term': 'Cycloparaffins'}, {'id': 'D006840', 'term': 'Hydrocarbons, Alicyclic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D039821', 'term': 'Monoterpenes'}, {'id': 'D013729', 'term': 'Terpenes'}, {'id': 'D008055', 'term': 'Lipids'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 14}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-01', 'completionDateStruct': {'date': '2014-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-01-11', 'studyFirstSubmitDate': '2016-01-08', 'studyFirstSubmitQcDate': '2016-01-11', 'lastUpdatePostDateStruct': {'date': '2016-01-12', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2016-01-12', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Spontaneous pain intensity [self-reported on a visual analog scale]', 'timeFrame': '0-20 minutes with a sampling frequency of 1/1 min', 'description': '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'}], 'secondaryOutcomes': [{'measure': 'Neurogenic inflammation [Measured by Laser speckle flowmetry in a 3x3 cm area]', 'timeFrame': '20-25 minutes post induction', 'description': '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.'}, {'measure': 'Heat hyperalgesia', 'timeFrame': '25-27.5 minutes post induction', 'description': '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'}, {'measure': 'Mechanical hyperalgesia', 'timeFrame': '27.5-30 minutes post induction', 'description': '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).'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Inflammation', 'Pruritus', 'Hyperalgesia']}, 'referencesModule': {'references': [{'pmid': '24664788', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '25792226', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '15931068', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '18440147', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '23963768', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '25861788', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '8520097', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '27260636', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': 'This study is designed as an experimental model in healthy humans.'}, 'eligibilityModule': {'stdAges': ['ADULT'], 'maximumAge': '50 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 18 healthy men and women aged 18-50 years willing to abstain from alcohol, nicotine, caffeine and pain medication 24 hours before experimental sessions\n\nExclusion Criteria:\n\n* Pregnancy\n* Skin disorders (e.g. contact eczema)\n* Chronic pain conditions\n* Drug addiction defined as the use of cannabis, opioids or other drugs\n* Previous neurologic, musculoskeletal or mental illnesses\n* Lack of ability to cooperate'}, 'identificationModule': {'nctId': 'NCT02653703', 'briefTitle': 'L-menthol as a Topical Counter-irritant to TRPA1-induced Neurogenic Inflammation and Pain', 'organization': {'class': 'OTHER', 'fullName': 'Aalborg University'}, 'officialTitle': 'High-concentration L-menthol as a Counter-irritant to TRPA1-induced Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde', 'orgStudyIdInfo': {'id': 'N-20130005'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Vehicle, topical ethanol 96%', 'description': 'Exposure: 10 % topical trans-cinnamaldehyde \\[CAS Number: 14371-10-9\\] Vehicle: 96% ethanol', 'interventionNames': ['Other: Vehicle, topical ethanol 96%']}, {'type': 'EXPERIMENTAL', 'label': 'Topical L-menthol 40%', 'description': 'Exposure: 10 % trans-cinnamaldehyde \\[CAS Number: 14371-10-9\\] Intervention: 40% l-menthol \\[CAS Number: 2216-51-5\\] Vehicle: 96% ethanol', 'interventionNames': ['Other: Topical L-menthol 40%']}], 'interventions': [{'name': 'Topical L-menthol 40%', 'type': 'OTHER', 'otherNames': ['Menthol'], 'description': 'Naturally occurring local anaesthetic, counterirritant and TPRM8-agonist. CAS Number: 2216-51-5', 'armGroupLabels': ['Topical L-menthol 40%']}, {'name': 'Vehicle, topical ethanol 96%', 'type': 'OTHER', 'description': 'Organic solvent CAS Number: 64-17-5', 'armGroupLabels': ['Vehicle, topical ethanol 96%']}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Aalborg University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor, PharmD, Ph.D.', 'investigatorFullName': 'Parisa Gazerani', 'investigatorAffiliation': 'Aalborg University'}}}}