Effect of Ketamine, Amitriptyline and Their Combination on Histaminergic and Non-histaminergic Itch

Itch Clinical Trial

Official title:

Effect of Ketamine, Amitriptyline and Their Combination on Histaminergic and Non-histaminergic Itch

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06245564
• Other study ID #: N-20230046
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 17, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2024
• Source: Aalborg University
• Contact: Silvia Lo Vecchio
• Phone: +4521397785
• Email: slv[@]hst.aau.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chronic itch affects approximately a fifth of the global population and is associated with substantial negative consequences for the affected individuals. Furthermore, there is a lack of efficient treat-ment options for chronic itch. Topical ketamine cream has been used successfully to relieve various forms of pain, and we hypothesize that topical ketamine relieves itch through a mechanism of action comparable to that in pain relief.

The aim of this project is to evaluate the effects of ketamine both alone and in combination with amitriptyline on histaminergic and non-histaminergic itch induced by histamine and cowhage, respectively.

Description:

The main action of ketamine, 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone, is to antagonize the glutamate N-methyl-D-aspartate (NMDA) receptors. In the clinical setting, topical ketamine cream has been used successfully to relieve various pathogenic forms of pain. In addition to its pain-relieving effects, the cream was also reported to have itch-relieving properties in a very limited study. However, its efficacy on itch has not been established, and the mechanism of action remains uncertain. Ketamine cream is used not only by itself, but also in conjunction with other analgesics. One of these is amitriptyline, which may enhance the analgesic effects of ketamine. The aim of this human experimental study is to use the well-characterized anesthetic Ketamine, both alone and in combination with amitriptyline, as a tool to modulate different histaminergic and non-histaminergic itch modalities evoked by histamine and cowhage.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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 (psychiatric diagnosis) 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.

• Participants had known allergy/discomfort to ketamine or amitriptyline

• Skin diseases

• Consumption of alcohol or painkillers 24 hours before the study days and between these

• Acute or chronic pain and itch

• Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical studies)

• Lack of ability to cooperate

Related Conditions & MeSH terms

• Itch

Intervention

Drug:
• Ketamine 0.5%
Ketamine cream 0.5% will be applied in a 4x4 area in the forearm of each participant.
• Amitriptyline
Amitriptyline cream 1% will be applied in a 4x4 area in the forearm of each participant.
• ketamine + amitriptyline
A cream containing ketamine 0.5%, amitriptyline 1%, will be applied in a 4x4 area in the forearm of each participant.

Other:
• Vehicle
A vehicle cream will be applied in a 4x4 area in the forearm of each participant.
• Histamine
After the cream removal, itch will be induced using histamine in the first session
• Cowhage
After the cream removal, itch will be induced using cowhage in the second session

Locations

Country	Name	City	State
Denmark	Silvia Lo Vecchio	Aalborg

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measuring itch by computerized Visual Analog Scale Scoring	We will ask the subjects 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".	Immediately after the intervention
Primary	Measuring pain by computerized Visual Analog Scale Scoring	We will ask the subjects 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".	Immediately after the intervention
Secondary	Superficial blood perfusion	Superficial blood perfusion (SBP) is measured by a Speckle contrast imager	Immediately after the intervention
Secondary	Touch Pleasantness	Pleasant touch sensation measured using a standardized sensory brush exerting a force of 200 to 400 mN.	Immediately after the intervention
Secondary	Mechanically evoked itch (MEI), intensity approach	MEI is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).	Immediately after the intervention
Secondary	Mechanically evoked itch, spatial approach	The von-Frey filament that better evokes the itch sensation during the assessment of mechanically evoked itch as well as a template of soft plastic are used to map the area of hyperkinesis in the test areas (forearms).	Immediately after the intervention
Secondary	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.	Immediately after the intervention
Secondary	Mechanical Pain Sensitivity (MPS), intensity approach	This test is conducted with the same pinprick set used to test the MPT.	Immediately after the intervention
Secondary	Mechanical Pain Sensitivity (MPS), spatial approach	The pinprick that was selected in the MPT as well as a template of soft plastic are used to map the area of hyperalgesia in the test areas (forearms).	Immediately after the intervention
Secondary	Cold Detection Thresholds (CDT)	The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device	Immediately after the intervention
Secondary	Warm Detection Thresholds (WDT)	The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device	Immediately after the intervention
Secondary	Cold Pain Thresholds (CPT)	The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device	Immediately after the intervention
Secondary	Heat Pain Thresholds (HPT)	The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device	Immediately after the intervention
Secondary	Pain to Supra-threshold Heat Stimuli (STHS)	The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device	Immediately after the intervention