Characterization of New Human Models of Non-histaminergic Itch

Itch Clinical Trial

Official title:

Characterization of New Human Models of Non-histaminergic Itch and Their Interaction With the TRPM8 Receptor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04515056
• Other study ID #: N-20200005
• Status: Completed
• Phase: N/A
• Start date: September 1, 2020
• Est. completion date: June 1, 2021

Study information

• Verified date: July 2021
• Source: Aalborg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this experiment the investigators would like to test a new new human itch model based on papain, and to characterize the sensory quality and temporary aspects of papain skin prick test (SPT) in comparison to the inactivated-cowhage delivery system.

Description:

The most used model of non-histaminergic itch is cowhage but this models presents several problems, such us the impossibility of standardizing the amount of the spicules inserted in the skin and the difficulty of obtaining the substance. These aspects bring us the necessity to find a new and more standardized model of non-histaminergic itch.

Papain is a cysteine protease extracted from papaya plant that is known to cause itch if applied to the skin. For these reasons the investigators would like to test a new new human itch model based on papain, and to characterize the sensory quality and temporary aspects of papain skin prick test (SPT) in comparison to the inactivated-cowhage delivery system.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy men and women

• 18-60 years

• Speak and understand English

Exclusion Criteria:

• Pregnancy or lactation

• Drug addiction defined as any use of cannabis, opioids or other addictive drugs

• Previous or current history of neurological, dermatological, immunological musculoskeletal, cardiac disorder or mental illnesses that may affect the results (e.g. neuropathy, muscular pain in the upper extremities, etc.).

• Lack of ability to cooperate

• Current use of medications that may affect the trial such as antihistamines, antipsychotics and pain killers, as well as systemic or topical steroids.

• Skin diseases

• Moles, scars or tattoos in the area to be treated or tested.

• Hypersensitivity to papaya and mango fruit, cashew nuts, rubber latex

• Consumption of alcohol or painkillers 24 hours before the study days and between these

• Acute or chronic pain

• Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical trials)

Related Conditions & MeSH terms

• Itch
• Papain
• Skin Prick Test (SPT)

Intervention

Drug:
• Papain 10 µg
The area will be exposed to 10 µg of papain.
• Papain 50 µg
The area will be exposed to 50 µg of papain.
• Papain 100 µg
The area will be exposed to 100 µg of papain.

Other:
• Vehicle
The area will be exposed to vehicle

Drug:
• Papain 1 SPT
Papain will be applied by 1 SPT prick thought the skin
• Papain 5 SPT
Papain will be applied by 5 SPT pricks thought the skin
• Papain 25 SPT
Papain will be applied by 25 SPT pricks thought the skin

Other:
• Cowhage
The last area will be exposed to cowage spicules (made chemically inert by autoclaving) soaked in 5 mg/ml papain solution.

Locations

Country	Name	City	State
Denmark	Aalborg University	Aalborg	Nordjylland

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Superficial blood perfusion	Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).	15 minutes
Primary	Measuring itch intensity by computerized Visual Analog Scale Scoring	The subjects will rate the sensation of itch on a 100 mm VAS scale ranging from 0 to 100 where 0 indicates "no itch" and 100 indicates "worst itch imaginable" and similarly for sensations of stinging/pricking and burning, both of which are frequently associated with the sensation of itch.	15 minutes
Primary	Measuring pain intensity by computerized Visual Analog Scale Scoring	The subjects will rate the sensation of pain on a 100 mm VAS scale ranging from 0 to 100 where 0 indicates "no pain" and 100 indicates "worst pain imaginable".	15 minutes
Primary	Measuring Alloknesis	Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 milliNewton of force). This stimulator is applied 0.5 cm outside the area of itch provocation.	15 minutes
Secondary	Measurement of Cold Detection Thresholds (CDT)	The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (cold sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	15 minutes
Secondary	Measurement of Cold Pain Thresholds (CPT)	The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (cold sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	15 minutes
Secondary	Measurement of Warm Detection Thresholds (WDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	15 minutes
Secondary	Measurement of Heat Pain Thresholds (HPT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	15 minutes
Secondary	Measurement of Pain to Supra-threshold Heat Stimuli	The tests will be conducted by using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. The subjects will have to rate the pain to two suprathreshold heat pain stimuli (starting and ending at 32°C with an increase and decrease of 5°C and 3 s plateau at 50°C).	15 minutes
Secondary	Measurement of Mechanical Pain Thresholds (MPT)	This test is conducted using a pin-prick set (Aalborg University, Aalborg).	15 minutes
Secondary	Measurement of Mechanical Pain Sensitivity (MPS)	This test is conducted using a pin-prick set (Aalborg University, Aalborg).	15 minutes
Secondary	Touch Pleasantness (TP)	Pleasant touch sensation measured using a standardized sensory brush (SENSELab Brush-05, Somedic AB, Hörby, Sweden) exerting a force of 200 to 400 mN.	15 minutes