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

The Role of the Interleukin-13 Pathways on Pain and Itch Sensitivity in Patients With Atopic Dermatitis and Healthy Volunteers

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 both healthy subjects and people with atopic dermatitis.

Study Overview

• Status: Recruiting
• Conditions: Itch
• Intervention / Treatment: Other: Histamine; Other: Cowhage; Other: bovine adrenal medulla (BAM8-22)

Detailed Description

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
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Silvia Lo Vecchio; Phone Number: 21397785; Email: slv@hst.aau.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9260
    • Not yet recruiting
    • Aalborg University
    • Contact: Silvia Lo Vecchio
  • Aalborg
    • Gistrup, Aalborg, Denmark, 9260
      • Recruiting
      • Aalborg University
      • Contact: Silvia Lo Vecchio, PhD; Phone Number: 21397785; Email: slv@hst.aau.dk
      • Contact: Botilla Markussen; Phone Number: 20567502; Email: bam@hst.aau.dk
      • Principal Investigator: Silvia Lo Vecchio, PhD
      • Sub-Investigator: Botilla Markussen
    • Gistrup, Aalborg, Denmark, 9260
      • Active, not recruiting
      • CNAP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy men and women
• 18-60 years

Exclusion Criteria:

• Pregnancy or lactation
• Drug addiction defined as any use of cannabis, opioids, or other drugs
• Previous or current history of neurological, dermatological (e.g., AD, psoriasis, etc.), immunological, musculoskeletal, cardiac disorder, or psychiatric diagnoses that may affect the results (e.g., neuropathy, muscular pain in the upper extremities, anxiety, depression, schizophrenia, etc.)
• Moles, wounds, scars, or tattoos in the area to be treated or tested
• Current use of medications that may affect the trial such as antihistamines and pain killers (use of antihistamines should be discontinued 72 hours before the experiment and all topical agents and emollients should be discontinued 24 hours before the experiment).
• Use of systemic and topical corticosteroids
• Consumption of alcohol or painkillers 24 hours before the study days and between these
• Acute or chronic pain
• Participation in other trials within one week of study entry (four weeks in the case of pharmaceutical trials)
• Lack of ability to cooperate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lebrikizumab; The initial doses will be subcutaneous Lebrikizumab 500 mg (two 250 mg injections) at both week 0 (baseline) and week 2, followed by 250 mg administered subcutaneously at week 4.

Other: Histamine; 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: Cowhage; Approximately 30-35 cowhage spicules will be manually inserted into the subject's skin.; Other: bovine adrenal medulla (BAM8-22); A small drop of BAM8-22 solution will be applied to a previously determined area on the volar forearm followed by a prick through the drop.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Superficial blood perfusion	Superficial blood perfusion (SBP) is measured by a Speckle contrast imager	Baseline
Superficial blood perfusion	Superficial blood perfusion (SBP) is measured by a Speckle contrast imager	10 minute after every itch induction
Wheal reaction	Wheal reaction measurement will be conducted immediately after the removal of pruritogens by measuring the longest diameter with a ruler.	10 minute after every itch induction
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.	Baseline
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)	Baseline
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).	Baseline
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).	10 minutes after every itch induction
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".	1 minute after every itch induction
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".	1 minute after every itch induction
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)	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline
Mechanical Pain Sensitivity (MPS)	This test is conducted with the same pinprick set used to test the MPT.	Baseline
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.	Baseline
Cold Detection Thresholds (CDT)	The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device	Baseliene
Warm Detection Thresholds (WDT)	The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testingdevice	Baseline
Cold Pain Thresholds (CPT)	The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device	Baseline
Heat Pain Thresholds (HPT)	The tests of thermal sensation will all be conducted using a TSA2 (Medoc Ltd, Israel) thermal sensory testing device	Baseline
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	Baseline

Collaborators and Investigators

• Sponsor: Aalborg University

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 10, 2024
• First Submitted That Met QC Criteria: July 10, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: May 30, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Histamine Agents; Neurotransmitter Agents; Histamine Agonists; Histamine
• Other Study ID Numbers: N-20240029

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No