Effect of Ketamine, Amitriptyline and Their Combination on Itch

NCT ID: NCT06245564

Last Updated: 2025-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-20
• Study Completion Date: 2024-12-31

Brief 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.

Detailed 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.

Conditions

Itch

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Cream application

This subproject will be conducted in two sessions one week apart. Each session will last approximately 3 hours. In each forearm of the participant, two 4x4 cm areas will be selected as Area of Interest (AOI). In these selected areas, the four different creams will be applied in a randomized position for 1½ hours. After the cream removal, itch will be induced using histamine in one session and cowhage in the other session (the order of histamine and cowhage will be randomized). During the application of the substances, the itch/pain elicited will be monitored for 10 minutes using a VAS (Visual analog scale). After the removal of the substances, measurements of SBP, TP, MEI, MPT, MPS, and thermal sensitivity will be conducted.

Group Type: EXPERIMENTAL

Ketamine 0.5%

Intervention Type: DRUG

Ketamine cream 0.5% will be applied in a 4x4 area in the forearm of each participant.

Amitriptyline

Intervention Type: DRUG

Amitriptyline cream 1% will be applied in a 4x4 area in the forearm of each participant.

ketamine + amitriptyline

Intervention Type: DRUG

A cream containing ketamine 0.5%, amitriptyline 1%, will be applied in a 4x4 area in the forearm of each participant.

Vehicle

Intervention Type: OTHER

A vehicle cream will be applied in a 4x4 area in the forearm of each participant.

Histamine

Intervention Type: OTHER

After the cream removal, itch will be induced using histamine in the first session

Cowhage

Intervention Type: OTHER

After the cream removal, itch will be induced using cowhage in the second session

Interventions

Ketamine 0.5%

Ketamine cream 0.5% will be applied in a 4x4 area in the forearm of each participant.

Intervention Type: DRUG

Amitriptyline

Amitriptyline cream 1% will be applied in a 4x4 area in the forearm of each participant.

Intervention Type: DRUG

ketamine + amitriptyline

A cream containing ketamine 0.5%, amitriptyline 1%, will be applied in a 4x4 area in the forearm of each participant.

Intervention Type: DRUG

Vehicle

A vehicle cream will be applied in a 4x4 area in the forearm of each participant.

Intervention Type: OTHER

Histamine

After the cream removal, itch will be induced using histamine in the first session

Intervention Type: OTHER

Cowhage

After the cream removal, itch will be induced using cowhage in the second session

Intervention Type: OTHER

Eligibility 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 (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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aalborg University

OTHER

Sponsor Role: lead

Responsible Party

Silvia Lo Vecchio

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Center for Neuroplasticity and Pain Faculty of Medicine, Aalborg University

Gistrup, Aalborg, Denmark

Countries

Denmark

Other Identifiers

N-20230046

Identifier Type: -

Identifier Source: org_study_id