Characterization of BAM8-22 as a New Surrogate Model of Non-histaminergic Itch

• ClinicalTrials.gov Identifier: NCT04588532
• Recruitment Status: Completed
• First Posted: October 19, 2020
• Last Update Posted: July 21, 2021
• Sponsor: Aalborg University
• Information provided by (Responsible Party): Giulia Erica Aliotta, Aalborg University

Study Description

Brief Summary:

With this experiment, the experimenter wish to asses if substance BAM8-22 (Bovine Adrenal Medulla) induce non-histaminergic itch.

Condition or disease	Intervention/treatment	Phase
Itch	Drug: BAM8-22; Drug: Histamine; Drug: Cowhage (Mucuna Pruriens); Drug: Doxepin	Not Applicable

Detailed Description:

With this experiment, the experimenter wish to establish if the substance BAM8-22 (Bovine Adrenal Medulla) induce a non-histaminergic itch by using the antihistamine Doxepin.

The experimenter will also compare itch and the response to antihistamine of BAM8-22, histamine and cowhage.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Characterization of Bovine Adrenal Medulla (BAM8-22) as a New Surrogate Model of Non-histaminergic Itch
• Actual Study Start Date: October 1, 2020
• Actual Primary Completion Date: May 1, 2021
• Actual Study Completion Date: June 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: doxepin; Drug: Doxepin + BAM8-22 Doxepin will be applied for 1.5 hrs followed by the application of BAM8-22. 20 µl of BAM8-22 will be applied to a previously determined area on the volar forearm followed by a prick through the drop Drug: Doxepin + Histamine Doxepin will be applied for 1.5 hrs followed by the application of Histamine. 20 µl of histamine will be applied to a previously determined area on the volar forearm followed by a prick through the drop Drug: Doxepin + Cowhage Doxepin will be applied for 1.5 hrs followed by the application of cowhage. 25/35 spicules of cowhage will be inserted in the skin through a gentle rubbing on a previously determined area on the volar forearm followed by a prick through the drop Drug: Doxepin + Placebo Doxepin will be applied for 1.5 hrs followed by the application of placebo. 20 µl of placebo will be applied to a previously determined area on the volar forearm followed by a prick through the drop	Drug: BAM8-22; Bovine Adrenal Medulla will be applied to 2 previously determined area on the volar forearm (one alone and one in combination with doxepin); Drug: Histamine; histamine will be applied to 2 previously determined area on the volar forearm (one alone and one in combination with doxepin); Drug: Cowhage (Mucuna Pruriens); cowhage spicules will be applied to 2 previously determined area on the volar forearm (one alone and one in combination with doxepin); Drug: Doxepin; Doxepin cream (antihistamine) will be applied in 4 areas on the volar forearm
Experimental: itch; Drug: BAM8-22 20 µl of BAM8-22 will be applied to a previously determined area on the volar forearm followed by a prick through the drop Drug: Histamine 20 µl of histamine will be applied to a previously determined area on the volar forearm followed by a prick through the drop Drug: Cowhage 25/35 spicules of cowhage will be inserted in the skin through a gentle rubbing on a previously determined area on the volar forearm followed by a prick through the drop Drug: Placebo 20 µl of placebo will be applied to a previously determined area on the volar forearm followed by a prick through the drop	Drug: BAM8-22; Bovine Adrenal Medulla will be applied to 2 previously determined area on the volar forearm (one alone and one in combination with doxepin); Drug: Histamine; histamine will be applied to 2 previously determined area on the volar forearm (one alone and one in combination with doxepin); Drug: Cowhage (Mucuna Pruriens); cowhage spicules will be applied to 2 previously determined area on the volar forearm (one alone and one in combination with doxepin)

Outcome Measures

Primary Outcome Measures :

1. superficial blood perfusion [ Time Frame: change from baseline, up to 10 minutes after the first session ]
   is measured by a speckle contrast imager (FLPI, Moor Instruments, England)
2. Warm Detection Threshold, and Heat Pain threshold [ Time Frame: change from baseline, up to 10 minutes after the first session ]
   the tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
3. Cold Detection Threshold and Cold Pain threshold [ Time Frame: change from baseline, up to 10 minutes after the first session ]
   the tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
4. Pain supra-threshold heat Stimuli [ Time Frame: change from baseline, up to 10 minutes after the first session ]
   the tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
5. hyperknesis (abnormal pruriceptive state) [ Time Frame: change from baseline, up to 10 minutes after the first session ]
   is measured by using a mildly pruritic, non-painful von Frey filaments of a predetermined intensity (generally 5-30 milliNewton of force)
6. mechanical pain threshold and sensitivity [ Time Frame: change from baseline, up to 10 minutes after the first session ]
   is performed using a pin-prick set (Aalborg University). The set consists of 8 needles each having a diameter of 0,6 mm and different force applications
7. itch rating [ Time Frame: change from baseline, up to 10 minutes after the first session ]
   the subject will rate the itch for 10 minutes by using a visual analog scale (VAS) on a tablet. this scale goes from 0 to 100. 0 indicates "no itch" and 100 indicates "worst imaginable itch"

Secondary Outcome Measures :

1. pain rating [ Time Frame: change from baseline, up to 10 minutes after the first session ]
   the subject will rate the pain for 10 minutes by using a visual analog scale (VAS) on a tablet. this scale goes from 0 to 100. 0 indicates "no pain" and 100 indicates "worst imaginable pain"

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy men and women
• 18-60 years
• Speak and understand English

Exclusion Criteria:

• Pregnancy or lactation
• Drug addiction defined as any use of cannabis, opioids or other 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.)
• Moles, wounds, scars or tattoos in the area to be treated or tested
• Lack of ability to cooperate •
• Current use of medications that may affect the trial such as antihistamines and pain killers.
• Skin diseases
• 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)

Contacts and Locations

Locations

Denmark

Aalborg University

Aalborg, Denmark, 9000

Sponsors and Collaborators

Aalborg University

More Information

• Responsible Party: Giulia Erica Aliotta, Principal investigator, PhD fellow, Aalborg University
• ClinicalTrials.gov Identifier: NCT04588532
• Other Study ID Numbers: N-20190062 2nd project
• First Posted: October 19, 2020
• Last Update Posted: July 21, 2021
• Last Verified: July 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Doxepin; Histamine; Histamine Agonists; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Sleep Aids, Pharmaceutical; Hypnotics and Sedatives; Central Nervous System Depressants; Antidepressive Agents, Tricyclic; Antidepressive Agents; Psychotropic Drugs; Histamine Antagonists