Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine
Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine
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.
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.