Influence of Antipruritics on the Dermal Blood Flow Response to Histamine, Cinnamaldehyde and Capsaicin.

NCT04399148 | Completed

• 1 other identifier: CCP18-3305-HIS-Part IIIA
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

In order to validate the accuracy and reliability of the histamine skin prick model for histaminergic itch and vasodilation, the dermal blood flow response induced by a histamine skin prick will be evaluated after the administration of certain antipruritics. Besides, the influence of these antipruritics on the dermal blood flow response induced by the topical application of cinnamaldehyde and capsaicin will be evaluated. Changes in dermal blood flow will be measured with laser speckle contrast imaging.

Conditions

Pruritus

Outcome Measures

Primary Outcomes (1)

• Change in dermal blood flow induced by histamine skin pricks, compared to baseline and placebo following the administration of different antipruritic drugs

  The dermal blood flow will be assessed before (baseline) and every 10 minutes during the hour following the skin pricks

Secondary Outcomes (1)

• Change in dermal blood flow induced by topical application of cinnamaldehyde and capsaicin, compared to baseline and placebo following the administration of different antipruritic drugs

  The dermal blood flow will be assessed before (baseline) and every 10 minutes during the hour following application

Study Arms (3)

Sequence 1

EXPERIMENTAL

Desloratadine - Aprepitant - Ketotifen

Drug: Desloratadine 5 mg; Drug: Aprepitant 125 mg; Drug: Ketotifen 1 MG

Sequence 2

EXPERIMENTAL

Aprepitant - Ketotifen - Desloratadine

Drug: Desloratadine 5 mg; Drug: Aprepitant 125 mg; Drug: Ketotifen 1 MG

Sequence 3

EXPERIMENTAL

Ketotifen - Desloratadine - Aprepitant

Drug: Desloratadine 5 mg; Drug: Aprepitant 125 mg; Drug: Ketotifen 1 MG

Interventions

Desloratadine 5 mg DRUG

Desloratadine (H1-antihistamine): oral tablet (1 x 5 mg), taken with 240 ml water, 4 hours prior to the histamine skin prick

Sequence 1; Sequence 2; Sequence 3

Aprepitant 125 mg DRUG

Aprepitant (NK1-antagonist): hard capsule (1 x 125 mg), taken with 240 ml water, 4 hours prior to the histamine skin prick

Sequence 1; Sequence 2; Sequence 3

Ketotifen 1 MG DRUG

Ketotifen (H1-antihistamine and mast cell stabilizer): capsule (1 x 1 mg), taken with 240 ml water, 4 hours prior to the histamine skin prick

Sequence 1; Sequence 2; Sequence 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is a white male ≥ 18 and ≤ 45 years of age at the time of screening
• Subject is a nonsmoker for at least 6 months prior to the study start
• Subject has a body mass index ≥ 18 and ≤ 30 kg/m2
• Subject has a clear increase in histamine-induced dermal blood flow; Subject has an increase in capsaicin- and cinnamaldehyde-induced dermal blood flow of at least 100% as determined during the screening visit
• Subject is judged to be in good health on the basis of medical history, physical examination and vital signs
• Subject understands the procedures and agrees to comply with them for the entire length of the study by giving written informed consent.

You may not qualify if:

• Subject has excessive hair growth on the volar surface of the forearm
• Subject has a past or present history of diffuse dermatological conditions including eczema, scleroderma, psoriasis, urticaria, dermatographism and dermatitis
• Subject has any abnormality on the skin of the forearm, possibly interfering with the study assessments including tattoos, keloids, tumors, ulcers, burns, flaps and grafts;
• Subject cannot avoid excessive tanning (any exposure to sunlight or a tanning bed which would cause a sunburn reaction) throughout the study and cannot cover the forearms 24 hours before and after each study visit
• Subject currently uses lotions, oils, depilatory preparations, makeup or other topical treatments on the arms and on a regular basis which cannot be discontinued for the duration of the study; subject has used any topical treatments within 7 days of the start of the study
• Subject has a past or present history of (symptomatic) asthma
• Subject has a history of severe allergic reactions to food or drugs or adverse experiences of a serious nature related to the administration of either a marketed or investigational drug, including histamine, cinnamaldehyde, capsaicin, desloratadine, ketotifen or aprepitant
• Subject currently uses any prescription or nonprescription drugs on a regular basis which cannot be discontinued for the duration of the study; subject has used any prescription or nonprescription medication within 14 days of the start of the study
• Subject is a habitual and heavy consumer of coffee or caffeinated beverages (more than approximately 4 cups of tea, coffee or cola per day) at the time of the study. Subjects who have reduced their consumption to ≤ 4 cups per day at least 1 week prior to enrollment may participate; Subjects who cannot refrain from caffeinated beverages 24 hours before the study visit
• Subject is unable to refrain from drinking alcohol 24 hours prior to histamine application, is currently a regular user (including "recreational use") of any illicit drugs, or has a history of drug (including alcohol) abuse. A drug screen will include amphetamines/ methamphetamines, methylenedioxymethamphetamine, benzodiazepines, barbiturates, cocaine, cannabis, tricyclic antidepressants, methadone and opiates
• Subject cannot refrain from being around second hand smoke 24 hours prior to histamine application or uses nicotine-containing products. Ex-smokers should have ceased smoking at least 6 months prior to screening
• Subject has any of the following vital sign measurements at screening: heart rate ≤ 40 or ≥ 100 beats/min, diastolic blood pressure ≤ 50 or ≥ 89 mmHg and/or systolic Blood Pressure ≤ 90 or ≥ 139 mmHg
• Subject has been involved in testing an investigational drug in another clinical study within the last 4 weeks or 5 half-lives
• Subject has evidence of a clinically significant active infection, fever of 38°C or above at the time of the study visits
• Subject has a history or current cardiovascular, respiratory, hepatic, renal, gastrointestinal or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

Center for Clinical Pharmacology

Leuven, 3000, Belgium

Location

MeSH Terms

Conditions

Pruritus

Interventions

desloratadine; Aprepitant; Ketotifen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiophenes; Sulfur Compounds; Organic Chemicals; Piperidines

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, cross-over study

Study Record Dates

• First Submitted: May 18, 2020
• First Posted: May 22, 2020
• Study Start: June 11, 2019
• Primary Completion: September 23, 2019
• Study Completion: September 23, 2019
• Last Updated: May 27, 2020

Record last verified: 2020-05

Locations

BE (1)