Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine

Phase 2TerminatedNCT03096444

Gil Yosipovitch13 enrolled

Overview

The purpose of this study is to examine the antipruritic efficacy of topical ketamine, amitriptyline, lidocaine, and a tri-combination of ketamine, amitriptyline and lidocaine (hereafter referred to as "KeAmLi") using non-histaminergic itch provocations in healthy volunteers. The primary outcome is itch reduction (AUC) between the vehicle and active treatment (KeAmLi-combo). Secondary outcomes include modality-specific analgesic properties of the topically applied ketamine, amitriptyline, lidocaine, and KeAmLi-combo to controlled quantitative thermal and mechanical stimuli, which can improve our understanding of the mechanism of action of these substances in the context of topical therapy.

This is a double-blind, vehicle-controlled study to evaluate the antipruritic efficacy of topical ketamine, amitriptyline, lidocaine, and a tri-combination of ketamine, amitriptyline and lidocaine (hereafter referred to as "KeAmLi") using non-histaminergic itch provocations in healthy volunteers. Each participant will be pre-treated with the vehicle and 4 active topical creams, over two study visits (3 treatments on the 1st visit and 2 treatment on the 2nd visit). Each treatment will be applied to the randomized forearm test area for 30 minute, and then sensory testing will be performed. Sensory testing includes thermal and mechanical stimuli, and itch induction using the plant cowhage. These tests will reveal mechanistic information and potential cellular and molecular targets for improved antipruritic and analgesic therapies.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Interventions

Ketamine HydrochlorideDRUG

2g of topical 10% Ketamine will be applied for 30 minutes on one 4x4cm area on the volar forearm in one of two study visits.

Amitriptyline HydrochlorideDRUG

2g of topical 5% Amitriptyline will be applied for 30 minutes on one 4x4cm area on the volar forearm in one of two study visits.

Lidocaine HydrochlorideDRUG

2g of topical 5% Lidocaine will be applied for 30 minutes on one 4x4cm area on the volar forearm in one of two study visits.

Ketamine hydrochloride, Amitriptyline hydrochloride, and Lidocaine hydrochlorideCOMBINATION_PRODUCT

2g of topical KeAmLi-combo (ketamine 10%, amitriptyline 5%, and lidocaine 5%) will be applied for 30 minutes on one 4x4cm area on the volar forearm in one of two study visits.

Lipoderm CreamDRUG

2g of topical vehicle (Lipoderm) will be applied for 30 minutes on one 4x4cm area on the volar forearm in one of two study visits.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Healthy subjects (absence of disease) between 18 and 50 years of age. 2. Must be in general good health with no disease or physical conditions that would impair evaluation of itch and pain perception. 3. No history of chronic itch or pain. 4. Must abstain from the use of any systemic or topical anti-histamine, steroid, or pain relief medications 48 hours prior to the study visits. 5. Must abstain from the use of moisturizers on the arms the day of study visit. Exclusion Criteria: 1. Individuals under 18 or over 50 years of age. 2. Inability to complete the required measures. 3. The presence of an itchy skin disease or a painful condition. 4. Diagnosis of diseased that would affect itch or pain perception (e.g. neuropathies). 5. Currently enrolled in any investigational study in which the subject is receiving any type of drug, biological, or non-drug therapy. 6. Use of oral, topical analgesics, or other medications known to interfere with itch or pain perception 48 hours prior to the study visits (e.g. antihistamines, anesthetics, anti-inflammatories, opioids, neuroleptics, etc.). 7. Use of emollients on the volar aspects of the forearms arms on the day of the study visit. 8. Use of anti-depressants, anti-psychotics, and illicit drugs. 9. Known history of neuropathy, uremia, uncontrolled thyroid disease, and diabetes mellitus. 10. Known history of anaphylactic shock, or allergy to cowhage and/or known adverse reactions to lidocaine (or other local anesthetics of the amide type), ketamine or amitriptyline.

Outcomes

Primary Outcomes

Peak Itch Intensity Between the Vehicle and Active Treatments (Individual and KeAmLi-combo).

Peak itch intensity between the vehicle and 4 other active treatments (individual ketamine, amitriptyline, or lidocaine, and KeAmLi-combo). Itch intensity was measured on a 100mm scale visual analog scale for 10 minutes. 0 was weighted with "no itch" and 100 was weighted with "most itch imaginable".

Time frame: 10 minutes

Secondary Outcomes

Thermal Threshold Detection (Warmth and Heat Pain)

Two standardized quantitative sensory tests are performed to measure warmth detection threshold (assesses the threshold of which warmth sensation is first detected) and heat pain threshold (assesses the threshold at which heat pain sensation is first detected). Measured in change in celsius.

Time frame: 3 minutes

Mechanical Thresholds (Mechanical Detection and Pain).

Assess mechanical detection and pain thresholds using von Frey filaments stimulators (measured in force mN) to calculate the final threshold as the geometric mean of five series of ascending and descending stimuli.

Time frame: 5 minutes