PapainNCT04515056
Characterization of New Human Models of Non-histaminergic Itch
A study testing Papain 10 µg, Papain 50 µg and Papain 100 µg in people with Papain and Itch, run by Aalborg University at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Papain, Itch, Skin Prick Test (SPT)
- What is being tested?
- Papain 10 µg, Papain 50 µg and Papain 100 µg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Sep 2020to 1 Jun 2021
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy men and women
- 18-60 years
- Speak and understand English
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Characterization of New Human Models of Non-histaminergic Itch and Their Interaction With the TRPM8 Receptor
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.
Read the detailed 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.
- Conditions
- Papain, Itch, Skin Prick Test (SPT)
- Being tested
- Papain 10 µg, Papain 50 µg, Papain 100 µg, Vehicle, Papain 1 SPT
- Medical subject headings
- Pruritus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Papain 10 µgDrug
The area will be exposed to 10 µg of papain.
Papain 50 µgDrug
The area will be exposed to 50 µg of papain.
Papain 100 µgDrug
The area will be exposed to 100 µg of papain.
VehicleOther
The area will be exposed to vehicle
Papain 1 SPTDrug
Papain will be applied by 1 SPT prick thought the skin
Papain 5 SPTDrug
Papain will be applied by 5 SPT pricks thought the skin
Papain 25 SPTDrug
Papain will be applied by 25 SPT pricks thought the skin
CowhageOther
The last area will be exposed to cowage spicules (made chemically inert by autoclaving) soaked in 5 mg/ml papain solution.
| Study group | Role | What they receive |
|---|---|---|
| Papain dosage | Experimental | In the 1st session, each of the middle forearms of the subject will be divided into two squared areas (4x4 cm). The two areas will be located 4 cm apart. Three areas will be exposed to 10, 50 or 100 µg of papain, while the last area will be used as control (exposed to a vehicle). Receives: Drug: Papain 10 µg; Drug: Papain 50 µg; Drug: Papain 100 µg; Other: Vehicle |
| Papain SPT | Experimental | Each forearm of the subject will be divided into two squared areas (4x4 cm). The provocations of three areas will be performed with 100 µg of papain by SPT lancets. To assess the potential importance of repeated pricks, papain will be applied by 1, 5 or 25 SPT pricks thought the skin. The last area will be exposed to cowage spicules (made chemically inert by autoclaving) soaked in 5 mg/ml papain solution. Receives: Drug: Papain 1 SPT; Drug: Papain 5 SPT; Drug: Papain 25 SPT; Other: Cowhage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Superficial blood perfusion
Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).
Measured: 15 minutes
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.
Measured: 15 minutes
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".
Measured: 15 minutes
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.
Measured: 15 minutes
Secondary outcomes (8)
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.
Measured: 15 minutes
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.
Measured: 15 minutes
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.
Measured: 15 minutes
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.
Measured: 15 minutes
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).
Measured: 15 minutes
Measurement of Mechanical Pain Thresholds (MPT)
This test is conducted using a pin-prick set (Aalborg University, Aalborg).
Measured: 15 minutes
Measurement of Mechanical Pain Sensitivity (MPS)
This test is conducted using a pin-prick set (Aalborg University, Aalborg).
Measured: 15 minutes
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.
Measured: 15 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2020
- Study start1 Sep 2020
- Primary completion1 Jun 2021
- Study completion1 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PapainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aalborg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Silvia Lo Vecchio, Aalborg University
- Investigators
- Silvia Lo Vecchio, Principal investigator, Aallborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04515056
- Sponsor's protocol ID
- N-20200005
- Status last verified
- Jul 2021
- First submitted
- 13 Aug 2020
- Last updated
- 9 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of New Human Models of Non-histaminergic Itch and Their Interaction With the TRPM8 Receptor
- ClinicalTrials.gov ID
- NCT04515056
- Acronym / sponsor ID
- N-20200005
- Conditions
- Papain, Itch, Skin Prick Test (SPT)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Aalborg UniversityUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Jun 2021 (actual)
- First posted
- 17 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Papain dosage | Experimental | Drug: Papain 10 µg, Drug: Papain 50 µg, Drug: Papain 100 µg, Other: VehicleIn the 1st session, each of the middle forearms of the subject will be divided into two squared areas (4x4 cm). The two areas will be located 4 cm apart. Three areas will be exposed to 10, 50 or 100 µg of papain, while the last area will be used as control (exposed to a vehicle). |
| Papain SPT | Experimental | Drug: Papain 1 SPT, Drug: Papain 5 SPT, Drug: Papain 25 SPT, Other: CowhageEach forearm of the subject will be divided into two squared areas (4x4 cm). The provocations of three areas will be performed with 100 µg of papain by SPT lancets. To assess the potential importance of repeated pricks, papain will be applied by 1, 5 or 25 SPT pricks thought the skin. The last area will be exposed to cowage spicules (made chemically inert by autoclaving) soaked in 5 mg/ml papain solution. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy men and women
- 18-60 years
- Speak and understand English
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Papain 10 µgThe area will be exposed to 10 µg of papain. | Drug | Papain dosage |
| Papain 50 µgThe area will be exposed to 50 µg of papain. | Drug | Papain dosage |
| Papain 100 µgThe area will be exposed to 100 µg of papain. | Drug | Papain dosage |
| VehicleThe area will be exposed to vehicle | Other | Papain dosage |
| Papain 1 SPTPapain will be applied by 1 SPT prick thought the skin | Drug | Papain SPT |
| Papain 5 SPTPapain will be applied by 5 SPT pricks thought the skin | Drug | Papain SPT |
| Papain 25 SPTPapain will be applied by 25 SPT pricks thought the skin | Drug | Papain SPT |
| CowhageThe last area will be exposed to cowage spicules (made chemically inert by autoclaving) soaked in 5 mg/ml papain solution. | Other | Papain SPT |
Primary outcome
Superficial blood perfusion
Time frame: 15 minutes
Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).
Measuring itch intensity by computerized Visual Analog Scale Scoring
Time frame: 15 minutes
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.
Measuring pain intensity by computerized Visual Analog Scale Scoring
Time frame: 15 minutes
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".
Measuring Alloknesis
Time frame: 15 minutes
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.
8 secondary outcomes
Measurement of Cold Detection Thresholds (CDT)
Time frame: 15 minutes
Measurement of Cold Pain Thresholds (CPT)
Time frame: 15 minutes
Measurement of Warm Detection Thresholds (WDT)
Time frame: 15 minutes
Measurement of Heat Pain Thresholds (HPT)
Time frame: 15 minutes
Measurement of Pain to Supra-threshold Heat Stimuli
Time frame: 15 minutes
Measurement of Mechanical Pain Thresholds (MPT)
Time frame: 15 minutes
Measurement of Mechanical Pain Sensitivity (MPS)
Time frame: 15 minutes
Touch Pleasantness (TP)
Time frame: 15 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2021.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Silvia Lo Vecchio principal investigator
Aallborg University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Papain 10 µg, Papain 50 µg and Papain 100 µg in people with Papain and Itch, run by Aalborg University at 1 site in Denmark.
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 3 inclusion and 11 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 9 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
Superficial blood perfusion (time frame: 15 minutes). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jul 2021.