Role of Interleukin-13 Pathways on Pain and Itch Sensitivity ( IL-13 )

N/AActive Not RecruitingNCT07017231

Aalborg University26 enrolled

Overview

Atopic dermatitis (AD) is as chronic, inflammatory skin disorder affecting 20% of the world's population. Intense itch and skin pain are the main symptoms. Research has shown that the proteins interleukins are involved in inflammation and itch in atopic dermatitis. The medicinal product called Lebrikizumab, used for treatment of AD, has shown to block the interleukin called IL-13. The purpose of this experiment is to evaluate the role of IL-13 in itch in people with atopic dermatitis.

Atopic dermatitis (AD) is as chronic, inflammatory skin disorder affecting 20% of the world's population. Intense itch and skin pain are the main symptoms. Research has shown that the interleukin-13 is involved in inflammation and itch in atopic dermatitis by increasing the neuronal sensitivity to pruritogens. However, the physiological mechanisms by which IL-13 increases the itch sensitivity are unclear. The aim of this project is to use, for the first time in humans, the monoclonal antibody Lebrikizumab that inhibits IL-13 with high affinity as a novel experimental tool to modulate the IL-13 pathway and evaluate its role in the transmission and processing of itch and pain.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Itching

Interventions

histamine dihydrochlorideOTHER

A small drop of histamine dihydrochloride (1%, in saline) will be applied to two previously determined areas followed by a prick through the drop.

CowhageOTHER

Approximately 30-35 cowhage spicules will be manually inserted into the subject's skin.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 18-60 years • The patients should have an AD according to diagnosis by a board-certified dermatologist, with an Eczema Area and Severity Index (EASI), a validated scoring tool that grades the physical signs of AD of at least 7. The project team will be specifically trained and evaluated in the EASI assessment to ensure interindividual consistency. Exclusion Criteria: * Pregnancy or lactation * Drug addiction defined as any use of cannabis, opioids, or other drugs Moles, wounds, scars, or tattoos in the area to be treated or tested * Treatment within two weeks before start of the experiment with topical corticosteroids or calcineurin inhibitors. * Treatment within two weeks before start of the experiment with topical treatments (excluding emollients) on the skin areas selected for testing (eight weeks if treated with systemic treatments for AD such as methotrexate or azathioprine) * Treatment with antihistamines 72 hours before start of the experiment * Previous or current history of neurological, musculoskeletal, cardiac disorder, or psychiatric diagnoses that may affect the results (e.g., neuropathy, muscular pain in the upper extremities, anxiety, depression, schizophrenia, etc.) * Current use of medications that may affect the trial such as antihistamines and painkillers (use of antihistamines must be discontinued 72 hours before the experiment and all topical agents and emollients must be discontinued 24 hours before the experiment). * Use of systemic corticosteroids * Consumption of alcohol or painkillers 24 hours before the study days and between these * Participation in other trials within one week of study entry (four weeks in the case of pharmaceutical trials) * Lack of ability to cooperate

Locations (1)

Center for Neuroplasticity and Pain Faculty of Medicine, Aalborg University Selma Lagerløfs Vej 249 9260 Gistrup, Denmark

Gistrup, Denmark

Outcomes

Primary Outcomes

Measuring itch by computerized Visual Analog Scale Scoring

The subjects will be asked to 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".

Time frame: Day 1

Superficial blood perfusion

Superficial blood perfusion (SBP) is measured by a Speckle contrast imager

Time frame: Day 1

Wheal reaction

Wheal reaction measurement will be conducted immediately after the removal of pruritogens by measuring the longest diameter with a ruler.

Time frame: Day 1

Average pruritis and pain numerical rating scale (NRS)

The subject will be asked to retrospectively rate the average and worst itch/pain on an 11-point scale ranging from 0 to 10 (0 = no pain and 10 = worst imaginable pain)experience they had during the last 7 days.

Time frame: Day 1

Skin peak pain numerical rating scale (SPP-NRS)

According to the SPP-NRS, the subject will be asked about "worst skin pain" they felt in the past 24 hours on an 11- point scale ranging from 0 to 10 (0 = no pain and 10 = worst imaginable pain)

Time frame: Day 1

Peak pruritus numerical rating scale (PP-NRS)

The subject will be asked about the "worst itch" they felt in the past 24 hours on an 11-point scale ranging from 0 to 10 (0 = no itch and 10 = worst imaginable itch)

Time frame: Day 1

Eczema Area and Severity Index (EASI)

This scale is used for patients with AD to assess severity and extent of the disease. The investigator/physician will assign scores based on redness, scratching, thickness, lichenification and percentage of affected body regions

Data from ClinicalTrials.gov

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Dermatology Life Quality Index (DLQI)

This questionnaire is a simple 10-question validated questionnaire that measures the impact of the skin disease on several aspects of the patient's life over the past week. The DLQI sum score is calculated by summing up the score of each item. Questions are scored on a four-point Likert scale: 0, not at all/not relevant; 1, a little; 2, a lot; and 3, very much.

Time frame: Day 1

Itch Severity Scale (ISS)

This is a seven items questionnaire: itch description, frequency, effect on sleep, effect on mood, effect on sexual desire/function, itch intensity using Likert scale and body surface area involved

Time frame: Day 1

Patient Oriented Eczema Measure (POEM)

POEM is a questionnaire used for patients' self-monitoring of AD severity. It asks about the frequency of seven symptoms (itch, sleep disturbance, dryness, flaking, weeping, or oozing, bleeding, and cracking) in the past seven days, and the patient has to choose between these answers: No days, 1-2 days, 3-4 days, 5-6 days, Every day

Time frame: Day 1

Mechanically evoked itch (MEI)

MEI is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).

Time frame: Day 1

Mechanically evoked itch (MEI)

MEI is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).

Time frame: Day 3

Measuring pain by computerized Visual Analog Scale Scoring

The subjects will be asked to 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".

Time frame: Day 3

Measuring pain by computerized Visual Analog Scale Scoring

The subjects will be asked to 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".

Time frame: Day 4

Superficial blood perfusion

Superficial blood perfusion (SBP) is measured by a Speckle contrast imager

Time frame: Day 3

Superficial blood perfusion

Superficial blood perfusion (SBP) is measured by a Speckle contrast imager

Time frame: Day 4

Wheal reaction

Wheal reaction measurement will be conducted immediately after the removal of pruritogens by measuring the longest diameter with a ruler.

Time frame: Day 3

Wheal reaction

Wheal reaction measurement will be conducted immediately after the removal of pruritogens by measuring the longest diameter with a ruler.

Time frame: Day 4

Average pruritis and pain numerical rating scale (NRS)

Time frame: Day 3

Average pruritis and pain numerical rating scale (NRS)

Time frame: Day 4

Skin peak pain numerical rating scale (SPP-NRS)

According to the SPP-NRS, the subject will be asked about "worst skin pain" they felt in the past 24 hours on an 11- point scale ranging from 0 to 10 (0 = no pain and 10 = worst imaginable pain)

Time frame: Day 3

Skin peak pain numerical rating scale (SPP-NRS)

According to the SPP-NRS, the subject will be asked about "worst skin pain" they felt in the past 24 hours on an 11- point scale ranging from 0 to 10 (0 = no pain and 10 = worst imaginable pain)

Time frame: Day 4

Peak pruritus numerical rating scale (PP-NRS)

The subject will be asked about the "worst itch" they felt in the past 24 hours on an 11-point scale ranging from 0 to 10 (0 = no itch and 10 = worst imaginable itch)

Time frame: Day 3

Peak pruritus numerical rating scale (PP-NRS)

The subject will be asked about the "worst itch" they felt in the past 24 hours on an 11-point scale ranging from 0 to 10 (0 = no itch and 10 = worst imaginable itch)

Time frame: Day 4

Eczema Area and Severity Index (EASI)

Time frame: Day 3

Eczema Area and Severity Index (EASI)

Time frame: Day 4

Dermatology Life Quality Index (DLQI)

Time frame: Day 3

Dermatology Life Quality Index (DLQI)

Time frame: Day 4

Itch Severity Scale (ISS)

This is a seven items questionnaire: itch description, frequency, effect on sleep, effect on mood, effect on sexual desire/function, itch intensity using Likert scale and body surface area involved

Time frame: Day 3

Itch Severity Scale (ISS)

This is a seven items questionnaire: itch description, frequency, effect on sleep, effect on mood, effect on sexual desire/function, itch intensity using Likert scale and body surface area involved

Time frame: Day 4

Patient Oriented Eczema Measure (POEM)

Time frame: Day 3

Patient Oriented Eczema Measure (POEM)

Time frame: Day 4

Mechanically evoked itch (MEI)

MEI is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).

Time frame: Day 4

Secondary Outcomes

Mechanical Pain Thresholds (MPT)

This test is conducted using a pinprick set. The set consists of 7 needles each with a diameter of 0.6 mm and different force applications: 8, 16, 32, 64, 128, 256, and 512 mN.

Time frame: Day 1

Mechanical Pain Sensitivity (MPS)

This test is conducted with the same pinprick set used to test the MPT.

Time frame: Day 1

Pressure Pain Thresholds (PPT)

Pressure will be applied by a handheld electronic pressure algometer (Somedic AB, Stockholm, Sweden) on to the supinator muscle on the left forearm.

Time frame: Day 1

Cold Detection Thresholds (CDT)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 1

Warm Detection Thresholds (WDT)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 1

Cold Pain Thresholds (CPT)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 1

Pain to Supra-threshold Heat Stimuli (STHS)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 1

Mechanical Pain Thresholds (MPT)

This test is conducted using a pinprick set. The set consists of 7 needles each with a diameter of 0.6 mm and different force applications: 8, 16, 32, 64, 128, 256, and 512 mN.

Time frame: Day 3

Mechanical Pain Thresholds (MPT)

This test is conducted using a pinprick set. The set consists of 7 needles each with a diameter of 0.6 mm and different force applications: 8, 16, 32, 64, 128, 256, and 512 mN.

Time frame: Day 4

Mechanical Pain Sensitivity (MPS)

This test is conducted with the same pinprick set used to test the MPT.

Time frame: Day 3

Mechanical Pain Sensitivity (MPS)

This test is conducted with the same pinprick set used to test the MPT.

Time frame: Day 4

Pressure Pain Thresholds (PPT)

Pressure will be applied by a handheld electronic pressure algometer (Somedic AB, Stockholm, Sweden) on to the supinator muscle on the left forearm.

Time frame: Day 3

Pressure Pain Thresholds (PPT)

Pressure will be applied by a handheld electronic pressure algometer (Somedic AB, Stockholm, Sweden) on to the supinator muscle on the left forearm.

Time frame: Day 4

Cold Detection Thresholds (CDT)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 3

Heat Pain Thrteshold

Time frame: Day 1

Cold Detection Thresholds (CDT)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 4

Warm Detection Thresholds (WDT)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 3

Warm Detection Thresholds (WDT)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 4

Heat Pain Thrteshold

Time frame: Day 3

Heat Pain Thrteshold

Time frame: Day 4

Pain to Supra-threshold Heat Stimuli (STHS)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 4

Cold Pain Thresholds (CPT)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 3

Cold Pain Thresholds (CPT)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 4

Pain to Supra-threshold Heat Stimuli (STHS)

The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device

Time frame: Day 3