ItchNCT06245564
Effect of Ketamine, Amitriptyline and Their Combination on Itch
A study testing Ketamine 0.5%, Amitriptyline and ketamine + amitriptyline in people with Itch, run by Aalborg University at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Itch
- What is being tested?
- Ketamine 0.5%, Amitriptyline and ketamine + amitriptyline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 20 Aug 2024to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy men and women
- 18-60 years
- Speak and understand English
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Neuroplasticity and Pain Faculty of Medicine, Aalborg University
Gistrup, Aalborg, 9260
About this study
Official title: Effect of Ketamine, Amitriptyline and Their Combination on Histaminergic and Non-histaminergic 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.
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine 0.5%Drug
Ketamine cream 0.5% will be applied in a 4x4 area in the forearm of each participant.
AmitriptylineDrug
Amitriptyline cream 1% will be applied in a 4x4 area in the forearm of each participant.
ketamine + amitriptylineDrug
A cream containing ketamine 0.5%, amitriptyline 1%, will be applied in a 4x4 area in the forearm of each participant.
VehicleOther
A vehicle cream will be applied in a 4x4 area in the forearm of each participant.
HistamineOther
After the cream removal, itch will be induced using histamine in the first session
CowhageOther
After the cream removal, itch will be induced using cowhage in the second session
| Study group | Role | What they receive |
|---|---|---|
| Cream application | Experimental | 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. Receives: Drug: Ketamine 0.5%; Drug: Amitriptyline; Drug: ketamine + amitriptyline; Other: Vehicle; Other: Histamine; Other: Cowhage |
What is being measured
The primary outcome is the main question the study is designed to answer.
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".
Measured: Immediately after the intervention
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".
Measured: Immediately after the intervention
Secondary outcomes (12)
Superficial blood perfusion
Superficial blood perfusion (SBP) is measured by a Speckle contrast imager
Measured: Immediately after the intervention
Touch Pleasantness
Pleasant touch sensation measured using a standardized sensory brush exerting a force of 200 to 400 mN.
Measured: Immediately after the intervention
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).
Measured: Immediately after the intervention
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).
Measured: Immediately after the intervention
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.
Measured: Immediately after the intervention
Mechanical Pain Sensitivity (MPS), intensity approach
This test is conducted with the same pinprick set used to test the MPT.
Measured: Immediately after the intervention
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).
Measured: Immediately after the intervention
Cold Detection Thresholds (CDT)
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Measured: Immediately after the intervention
Warm Detection Thresholds (WDT)
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Measured: Immediately after the intervention
Cold Pain Thresholds (CPT)
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Measured: Immediately after the intervention
Heat Pain Thresholds (HPT)
The tests of thermal sensation will all be conducted using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device
Measured: Immediately after the intervention
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
Measured: Immediately after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2024
- Study start20 Aug 2024
- Primary completion31 Dec 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ItchStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- In each participant, the four different creams will be applied in a randomized position. After the cream removal, itch will be induced using histamine in one session and cowhage in the other session.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aalborg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Silvia Lo Vecchio, Aalborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06245564
- Sponsor's protocol ID
- N-20230046
- Status last verified
- Oct 2024
- First submitted
- 25 Jan 2024
- Last updated
- 30 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Ketamine, Amitriptyline and Their Combination on Histaminergic and Non-histaminergic Itch
- ClinicalTrials.gov ID
- NCT06245564
- Acronym / sponsor ID
- N-20230046
- Conditions
- Itch
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Aalborg UniversityUniversity, hospital or other
- Study start
- 20 Aug 2024 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 7 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- In each participant, the four different creams will be applied in a randomized position. After the cream removal, itch will be induced using histamine in one session and cowhage in the other session.
| Arm | Type | Receives |
|---|---|---|
| Cream application | Experimental | Drug: Ketamine 0.5%, Drug: Amitriptyline, Drug: ketamine + amitriptyline, Other: Vehicle, Other: Histamine, Other: CowhageThis 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy men and women
- 18-60 years
- Speak and understand English
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamine 0.5%Ketamine cream 0.5% will be applied in a 4x4 area in the forearm of each participant. | Drug | Cream application |
| AmitriptylineAmitriptyline cream 1% will be applied in a 4x4 area in the forearm of each participant. | Drug | Cream application |
| ketamine + amitriptylineA cream containing ketamine 0.5%, amitriptyline 1%, will be applied in a 4x4 area in the forearm of each participant. | Drug | Cream application |
| VehicleA vehicle cream will be applied in a 4x4 area in the forearm of each participant. | Other | Cream application |
| HistamineAfter the cream removal, itch will be induced using histamine in the first session | Other | Cream application |
| CowhageAfter the cream removal, itch will be induced using cowhage in the second session | Other | Cream application |
Primary outcome
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".
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".
12 secondary outcomes
Superficial blood perfusion
Time frame: Immediately after the intervention
Touch Pleasantness
Time frame: Immediately after the intervention
Mechanically evoked itch (MEI), intensity approach
Time frame: Immediately after the intervention
Mechanically evoked itch, spatial approach
Time frame: Immediately after the intervention
Mechanical Pain Thresholds (MPT)
Time frame: Immediately after the intervention
Mechanical Pain Sensitivity (MPS), intensity approach
Time frame: Immediately after the intervention
Mechanical Pain Sensitivity (MPS), spatial approach
Time frame: Immediately after the intervention
Cold Detection Thresholds (CDT)
Time frame: Immediately after the intervention
Warm Detection Thresholds (WDT)
Time frame: Immediately after the intervention
Cold Pain Thresholds (CPT)
Time frame: Immediately after the intervention
Heat Pain Thresholds (HPT)
Time frame: Immediately after the intervention
Pain to Supra-threshold Heat Stimuli (STHS)
Time frame: Immediately after the intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketamine 0.5%, Amitriptyline and ketamine + amitriptyline in people with Itch, run by Aalborg University at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measuring itch by computerized Visual Analog Scale Scoring (time frame: Immediately after the intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.