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

NCT04554888 | Completed DMC

• 1 other identifier: N-20200005 2nd project
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In this experiment the investigators would like to assess if papain induces an itch sensation comparable to the itch sensation induced by cowhage and to confirm that the mechanism of action of papain follows the non-histaminergic pathway.

Conditions

Itch

Outcome Measures

Primary Outcomes (4)

• Superficial blood perfusion

  Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).

  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.

  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".

  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.

  15 minutes

Secondary Outcomes (8)

• Measurement of Cold Detection Thresholds (CDT)

  15 minutes

• Measurement of Cold PainThresholds (CPT)

  15 minutes

• Measurement of Heat Pain Thresholds (HPT)

  15 minutes

• Measurement of Warm Detection Thresholds (WDT)

  15 minutes

• Measurement of Pain to Supra-threshold Heat Stimuli

  15 minutes

Study Arms (2)

Doxepin Application

EXPERIMENTAL

During the session each forearm of the subject will be divided into four squared areas (2.5x2.5 cm), see Figure 4. Four of the areas will be treated with doxepin for 1 hour and 30 minutes (with a patch to deposit 1.2 grams of cream). Each patch will be covered with Tegaderm I.V., an occlusive, adhesive dressing (3M), for at least 1½ hours 48. At the end of the pre-treatment period, the patches will be removed and the skin will be cleaned with alcohol.

Drug: Doxepin Topical

Itch Induction

EXPERIMENTAL

After Doxepin removal, Then tests with papain, cowhage, histamine or vehicle will be conducted. Each substance will be randomly applied in two areas, one pretreated with doxepin and one with no pre-treatment.

Drug: Papain; Drug: Histamine; Other: Cowhage

Interventions

Doxepin Topical DRUG

Four of the areas will be treated with doxepin for 1 hour and 30 minutes (with a patch to deposit 1.2 grams of cream). Each patch will be covered with Tegaderm I.V., an occlusive, adhesive dressing (3M), for at least 1½ hours

Doxepin Application

Papain DRUG

Papain will be applied by 1 SPT prick thought the skin

Itch Induction

Histamine DRUG

Histamine will be applied by 1 SPT prick thought the skin

Itch Induction

Cowhage OTHER

Cowhage spicules are 1-2 mm in length and have diameter of 1-3 µm at their tip. 30-35 spicules are gently rubbed into a 1 cm diameter skin area.

Itch Induction

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy men and women
• years
• Speak and understand English

You may not qualify if:

• 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)

Sponsors & Collaborators

• Aalborg University: lead

Study Sites (1)

Aalborg University

Aalborg, North Denmark, 9000, Denmark

Location

MeSH Terms

Conditions

Pruritus

Interventions

Doxepin; Papain; Histamine

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Oxepins; Ethers, Cyclic; Ethers; Organic Chemicals; Dibenzoxepins; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cysteine Endopeptidases; Cysteine Proteases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Endopeptidases; Biogenic Monoamines; Biogenic Amines; Amines; Ethylamines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Autacoids; Inflammation Mediators; Biological Factors

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Assistant Professor

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: September 18, 2020
• Study Start: March 1, 2022
• Primary Completion: May 31, 2022
• Study Completion: June 30, 2022
• Last Updated: July 20, 2022

Record last verified: 2022-07

Locations

DK (1)