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Completed

NCT Number: NCT06245564

Effect of Ketamine, Amitriptyline and Their Combination on Itch

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.

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Key information

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Center for Neuroplasticity and Pain Faculty of Medicine, Aalborg University

Gistrup, Aalborg, 9260, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ketamine 0.5%

Drug

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

Amitriptyline

Drug

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

ketamine + amitriptyline

Drug

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

Vehicle

Other

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

Histamine

Other

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

Cowhage

Other

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

Primary outcomes

  1. Measuring itch by computerized Visual Analog Scale Scoring

    Time frame: Immediately after the intervention

    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".

  2. Measuring pain by computerized Visual Analog Scale Scoring

    Time frame: Immediately after the intervention

    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".

Secondary outcomes

  1. Superficial blood perfusion

    Time frame: Immediately after the intervention

    Superficial blood perfusion (SBP) is measured by a Speckle contrast imager

  2. Touch Pleasantness

    Time frame: Immediately after the intervention

    Pleasant touch sensation measured using a standardized sensory brush exerting a force of 200 to 400 mN.

  3. Mechanically evoked itch (MEI), intensity approach

    Time frame: Immediately after the intervention

    MEI is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).

  4. Mechanically evoked itch, spatial approach

    Time frame: Immediately after the intervention

    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).

  5. Mechanical Pain Thresholds (MPT)

    Time frame: Immediately after the intervention

    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.

  6. Mechanical Pain Sensitivity (MPS), intensity approach

    Time frame: Immediately after the intervention

    This test is conducted with the same pinprick set used to test the MPT.

  7. Mechanical Pain Sensitivity (MPS), spatial approach

    Time frame: Immediately after the intervention

    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).

  8. Cold Detection Thresholds (CDT)

    Time frame: Immediately after the intervention

    The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device

  9. Warm Detection Thresholds (WDT)

    Time frame: Immediately after the intervention

    The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device

  10. Cold Pain Thresholds (CPT)

    Time frame: Immediately after the intervention

    The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device

  11. Heat Pain Thresholds (HPT)

    Time frame: Immediately after the intervention

    The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device

  12. Pain to Supra-threshold Heat Stimuli (STHS)

    Time frame: Immediately after the intervention

    The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device

Sponsors and collaborators

Lead sponsor

Aalborg University

Other

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2024
Study completion
2024
First posted
Feb 7, 2024
Registry last updated
Jan 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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