ItchNCT03943407
Characterization of the Toll-like Receptor 7-agonist Imiquimod 3.75% As a New Surrogate Model of Itch
A study testing Zyclara 3.75 % Topical Cream, Prudoxin and Histamine in people with Itch, run by Aalborg University at 1 site in Denmark.
Trial summary
The aim of this research project is to design a new model of human itch by application of Zyclara cream. Further, the aim is to characterize the model and to verify if the mechanism of action of imiquimod follows the histaminergic or non-histaminergic pathway by using the anti-histamine drug doxepin. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Itch
- What is being tested?
- Zyclara 3.75 % Topical Cream, Prudoxin and Histamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Nov 2019to Jun 2022
- 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 drugs
- Previous or current neurologic, musculoskeletal or mental illnesses
- Lack of ability to cooperate
- Current use of medications that may affect the trial
- Skin diseases
Show all 9Show fewer
- 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
The aim of this research project is to design a new model of human itch by application of Zyclara cream. Further, the aim is to characterize the model and to verify if the mechanism of action of imiquimod follows the histaminergic or non-histaminergic pathway by using the anti-histamine drug doxepin. The last goal is to evaluate the interaction between the activation of TLR7 receptor and the activation of TRPA1 and TRPM8 receptors, which are two of the most important receptors involved in the transduction of noxious stimuli, and to evaluate to which extent these three channel populations functionally overlap.
- Conditions
- Itch
- Being tested
- Zyclara 3.75 % Topical Cream, Prudoxin, Histamine, Cowhage, L-menthol
- Keywords
- Imiquimod, Doxepin, Trans-cinnamaldehyde (CA), L-menthol, Histamine, Cowhage
- Medical subject headings
- Pruritus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zyclara 3.75 % Topical CreamDrug
The cream will be applied on 4x4 cm squared areas on the volar forearm. The cream will be left in place for 2h, 1 h or 30 min (sub-study 1) after which it will be removed. The technical and security procedures will be conducted in accordance with the manufacturer's instructions.
PrudoxinDrug
The anti-histamine cream Prudoxin, containing 5% doxepin hydrochloride (1 g contains 50 mg of doxepin) (Healthpoint, San Antonio, TX) will be applied on the volar forearm. Two adhesive patches 4×4 cm (1mm thick, 3M foam adhesive tape, 3M, St. Paul, MN) each with a 3.5×3.5 cm center cut out (to deposit 1.2 grams of cream) will be each placed 3 cm distal and 3 cm proximal to the center of the volar aspect of each arm. Each patch will be covered with Tegaderm I.V., an occlusive, adhesive dressing (3M), for at least 1 h and 30 minutes.
HistamineOther
To deliver histamine, standard allergy skin prick test (SPT) lancets are applied. The lancets have a 1 mm shouldered tip adapt to introduce a small amount of test substance extremely locally and approximately at the dermo-epidermal junction. . A small drop of histamine dihydrochloride (1%, in saline) will be applied to a previously determined area on the volar forearm followed by a prick through the drop.
CowhageOther
Cowhage spicules are 1-2 mm in length and have diameter of 1-3 um at their tip. The active substance delivered (mucunain) has been calculated to be in the nanogram range. The insertion of cowhage spicule(s) rapidly and consistently produces itch with no or very little flare reaction. This insertion is conducted by forceps using a stereo-microscope, and 30-35 spicules are gently rubbed into a 1 cm diameter skin area.
L-mentholOther
L-menthol (≥99.9%, TRPM8 agonist; (Sigma Aldrich, Broendby, Denmark) is dissolved in 96% ethanol at concentrations of 40%(w/v) L-menthol. A 1 mL aliquot is dispensed onto a 3 × 3 cm cotton pad and placed on a 6 × 6 cm sheet of medical tape. In between the cotton pad and the medical tape, a layer of parafilm will be added to avoid evaporation. This configuration was subsequently applied for 1 h.
Trans-cinnamaldehyde (CA)Other
CA will be obtained from Sigma Aldrich (Brøndby, Denmark) and dissolved in 90% ethanol at a concentration of 10% (vol/vol) CA. One ml aliquot of CA is dispensed onto a 3x3 cm cotton pad and placed on a 5x5 cm sheet of medical tape. Between the cotton pad and the tape, a layer of plastic film will be added to inhibit the evaporation of the solutions. This configuration will be applied for 1 h.
| Study group | Role | What they receive |
|---|---|---|
| Zyclara/vehicle | Experimental | All subjects will be treated with Zyclara cream (Imiquimod 3.75%) and vehicle. Receives: Drug: Zyclara 3.75 % Topical Cream |
| Zyclara/Doxepin | Experimental | All subjects will be treated with the topical antihistamine cream (Prudoxin, containing 5% doxepin hydrochloride, Healthpoint, San Antonio, TX) or a placebo cream. After removal, subjects will be treated with Zyclara cream Receives: Drug: Zyclara 3.75 % Topical Cream; Drug: Prudoxin |
| Zyclara/Histamine/Cowage | Experimental | All subjects will be treated with Zyclara cream, vehicle cream, histamine and cowhage Receives: Drug: Zyclara 3.75 % Topical Cream; Other: Histamine; Other: Cowhage |
| Zyclara/L-menthol/trans-cinnamaldehyde | Experimental | All subjects will be treated with Zyclara cream (Imiquimod 3.75%) and vehicle. After removal, subjects will be treated with L/menthol and trans-cinnamaldehyde Receives: Drug: Zyclara 3.75 % Topical Cream; Other: L-menthol; Other: Trans-cinnamaldehyde (CA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Superficial blood perfusion by by a Speckle contrast imager (FLPI, Moor Instruments, England).
Two pictures will be taken: one with the sensor placed approximately 35 cm above the induction area and one with the sensor placed approximately 20 cm above the induction area.
Measured: Change from baseline, to maximum 19 days after intervention
Trans-epidermal Water Loss (TEWL)
a 2x2 cm hollow probe with two small humidity gauges and two thermometers is placed lightly on the skin for 10-25 seconds. These establish a precise humidity gradient in a 2 cm vicinity of the skin, representative for the point-loss of water though the epidermis.
Measured: Change from baseline, to maximum 19 days after intervention
Neurogenic Inflammatory Response and Pigmentation
treatment will be measured with a spectrometer designed for cutaneous use (ColorMeter, DSM II; Cortex Technology, Hadsund, Denmark).
Measured: Change from baseline, to maximum 19 days after intervention
Measuring Alloknesis
Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).
Measured: Change from baseline, to maximum 19 days after intervention
Thermal measurements (cold and warm detection thresholds, cold and heat pain thresholds)
The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Measured: Change from baseline, to maximum 19 days after intervention
Measurement of Pain to Supra-threshold Heat Stimuli
The test will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Measured: Change from baseline, to maximum 19 days after intervention
Measurement of Mechanical Detection Thresholds, Mechanical Pain Threshold and sensitivity
These tests are conducted using a set of 20 different von Frey hairs (North Coast Medical, Gilroy, CA) with exerted forces ranging from .008g to 300g.
Measured: Change from baseline, to maximum 19 days after intervention
Secondary outcomes (2)
Measurement of Itch rating by Computerized Visual Analog Scale Scoring
We will ask the subjects to rate the sensation of itch on a VAS scale ranging from 0 to 10 where 0 indicates "no itch" and 10 indicates "worst itch imaginable"to 10 where 0 indicates "no itch" and 10 indicates "worst itch imaginable" and similarly for sensations of stinging/pricking and burning, both of which are frequently associated with the sensation of itch or pain.
Measured: Change from baseline, to maximum 19 days after intervention
Measurement of pain rating by Computerized Visual Analog Scale Scoring
the subjects will be asked to rate the sensation of pain on a VAS scale ranging from 0 to 10 where "0" is no pain and "10" is the worst pain.
Measured: Change from baseline, to maximum 19 days after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2019
- Study start1 Nov 2019
- Primary completionJun 2021 (estimated)
- Study completionJun 2022 (estimated)
Why it stopped: The Imiquimod 3.75% was ineffective
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ItchStudies 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aalborg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Silvia Lo Vecchio, Aalborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03943407
- Sponsor's protocol ID
- N-20190029
- Status last verified
- Jan 2021
- First submitted
- 7 May 2019
- Last updated
- 22 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of the Toll-like Receptor 7-agonist Imiquimod 3.75% As a New Surrogate Model of Itch
- ClinicalTrials.gov ID
- NCT03943407
- Acronym / sponsor ID
- N-20190029
- Conditions
- Itch
- Keywords
- Imiquimod, Doxepin, Trans-cinnamaldehyde (CA), L-menthol, Histamine, Cowhage
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The Imiquimod 3.75% was ineffective
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Aalborg UniversityUniversity, hospital or other
- Study start
- 1 Nov 2019 (actual)
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 9 May 2019 (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.
The aim of this research project is to design a new model of human itch by application of Zyclara cream. Further, the aim is to characterize the model and to verify if the mechanism of action of imiquimod follows the histaminergic or non-histaminergic pathway by using the anti-histamine drug doxepin. The last goal is to evaluate the interaction between the activation of TLR7 receptor and the activation of TRPA1 and TRPM8 receptors, which are two of the most important receptors involved in the transduction of noxious stimuli, and to evaluate to which extent these three channel populations functionally overlap.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Zyclara/vehicle | Experimental | Drug: Zyclara 3.75 % Topical CreamAll subjects will be treated with Zyclara cream (Imiquimod 3.75%) and vehicle. |
| Zyclara/Doxepin | Experimental | Drug: Zyclara 3.75 % Topical Cream, Drug: PrudoxinAll subjects will be treated with the topical antihistamine cream (Prudoxin, containing 5% doxepin hydrochloride, Healthpoint, San Antonio, TX) or a placebo cream. After removal, subjects will be treated with Zyclara cream |
| Zyclara/Histamine/Cowage | Experimental | Drug: Zyclara 3.75 % Topical Cream, Other: Histamine, Other: CowhageAll subjects will be treated with Zyclara cream, vehicle cream, histamine and cowhage |
| Zyclara/L-menthol/trans-cinnamaldehyde | Experimental | Drug: Zyclara 3.75 % Topical Cream, Other: L-menthol, Other: Trans-cinnamaldehyde (CA)All subjects will be treated with Zyclara cream (Imiquimod 3.75%) and vehicle. After removal, subjects will be treated with L/menthol and trans-cinnamaldehyde |
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 (9 listed)
- Pregnancy or lactation
- Drug addiction defined as any use of cannabis, opioids or other drugs
- Previous or current neurologic, musculoskeletal or mental illnesses
- Lack of ability to cooperate
- Current use of medications that may affect the trial
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 |
|---|---|---|
| Zyclara 3.75 % Topical CreamThe cream will be applied on 4x4 cm squared areas on the volar forearm. The cream will be left in place for 2h, 1 h or 30 min (sub-study 1) after which it will be removed. The technical and security procedures will be conducted in accordance with the manufacturer's instructions. | Drug | Zyclara/Doxepin, Zyclara/Histamine/Cowage, Zyclara/L-menthol/trans-cinnamaldehyde, Zyclara/vehicle |
| PrudoxinThe anti-histamine cream Prudoxin, containing 5% doxepin hydrochloride (1 g contains 50 mg of doxepin) (Healthpoint, San Antonio, TX) will be applied on the volar forearm. Two adhesive patches 4×4 cm (1mm thick, 3M foam adhesive tape, 3M, St. Paul, MN) each with a 3.5×3.5 cm center cut out (to deposit 1.2 grams of cream) will be each placed 3 cm distal and 3 cm proximal to the center of the volar aspect of each arm. Each patch will be covered with Tegaderm I.V., an occlusive, adhesive dressing (3M), for at least 1 h and 30 minutes. | Drug | Zyclara/Doxepin |
| HistamineTo deliver histamine, standard allergy skin prick test (SPT) lancets are applied. The lancets have a 1 mm shouldered tip adapt to introduce a small amount of test substance extremely locally and approximately at the dermo-epidermal junction. . A small drop of histamine dihydrochloride (1%, in saline) will be applied to a previously determined area on the volar forearm followed by a prick through the drop. | Other | Zyclara/Histamine/Cowage |
| CowhageCowhage spicules are 1-2 mm in length and have diameter of 1-3 um at their tip. The active substance delivered (mucunain) has been calculated to be in the nanogram range. The insertion of cowhage spicule(s) rapidly and consistently produces itch with no or very little flare reaction. This insertion is conducted by forceps using a stereo-microscope, and 30-35 spicules are gently rubbed into a 1 cm diameter skin area. | Other | Zyclara/Histamine/Cowage |
| L-mentholL-menthol (≥99.9%, TRPM8 agonist; (Sigma Aldrich, Broendby, Denmark) is dissolved in 96% ethanol at concentrations of 40%(w/v) L-menthol. A 1 mL aliquot is dispensed onto a 3 × 3 cm cotton pad and placed on a 6 × 6 cm sheet of medical tape. In between the cotton pad and the medical tape, a layer of parafilm will be added to avoid evaporation. This configuration was subsequently applied for 1 h. | Other | Zyclara/L-menthol/trans-cinnamaldehyde |
| Trans-cinnamaldehyde (CA)CA will be obtained from Sigma Aldrich (Brøndby, Denmark) and dissolved in 90% ethanol at a concentration of 10% (vol/vol) CA. One ml aliquot of CA is dispensed onto a 3x3 cm cotton pad and placed on a 5x5 cm sheet of medical tape. Between the cotton pad and the tape, a layer of plastic film will be added to inhibit the evaporation of the solutions. This configuration will be applied for 1 h. | Other | Zyclara/L-menthol/trans-cinnamaldehyde |
Primary outcome
Superficial blood perfusion by by a Speckle contrast imager (FLPI, Moor Instruments, England).
Time frame: Change from baseline, to maximum 19 days after intervention
Two pictures will be taken: one with the sensor placed approximately 35 cm above the induction area and one with the sensor placed approximately 20 cm above the induction area.
Trans-epidermal Water Loss (TEWL)
Time frame: Change from baseline, to maximum 19 days after intervention
a 2x2 cm hollow probe with two small humidity gauges and two thermometers is placed lightly on the skin for 10-25 seconds. These establish a precise humidity gradient in a 2 cm vicinity of the skin, representative for the point-loss of water though the epidermis.
Neurogenic Inflammatory Response and Pigmentation
Time frame: Change from baseline, to maximum 19 days after intervention
treatment will be measured with a spectrometer designed for cutaneous use (ColorMeter, DSM II; Cortex Technology, Hadsund, Denmark).
Measuring Alloknesis
Time frame: Change from baseline, to maximum 19 days after intervention
Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).
Thermal measurements (cold and warm detection thresholds, cold and heat pain thresholds)
Time frame: Change from baseline, to maximum 19 days after intervention
The tests for thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Measurement of Pain to Supra-threshold Heat Stimuli
Time frame: Change from baseline, to maximum 19 days after intervention
The test will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Measurement of Mechanical Detection Thresholds, Mechanical Pain Threshold and sensitivity
Time frame: Change from baseline, to maximum 19 days after intervention
These tests are conducted using a set of 20 different von Frey hairs (North Coast Medical, Gilroy, CA) with exerted forces ranging from .008g to 300g.
2 secondary outcomes
Measurement of Itch rating by Computerized Visual Analog Scale Scoring
Time frame: Change from baseline, to maximum 19 days after intervention
Measurement of pain rating by Computerized Visual Analog Scale Scoring
Time frame: Change from baseline, to maximum 19 days after intervention
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Zyclara 3.75 % Topical Cream, Prudoxin and Histamine in people with 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 9 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: withdrawn, as of the sponsor's last update on 22 Nov 2024. 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 was withdrawn before enrolling participants, so there are no results.
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 by by a Speckle contrast imager (FLPI, Moor Instruments, England). (time frame: Change from baseline, to maximum 19 days after intervention). The study lists 7 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 22 Nov 2024.