Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine

Gil Yosipovitch

Status and phase: Terminated; Phase 2

Conditions: Pruritus

Treatments: Drug: Amitriptyline Hydrochloride; Drug: Ketamine Hydrochloride; Drug: Lidocaine Hydrochloride; Drug: Lipoderm Cream; Combination Product: Ketamine hydrochloride, Amitriptyline hydrochloride, and Lidocaine hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT03096444

20170087

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 13 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

13 participants in 5 patient groups, including a placebo group

Topical KeAmLi combo

Experimental group

Description:

Topical KeAmLi-combo (ketamine 10%, amitriptyline 5%, and lidocaine 5%) will be applied to one four 4 x 4 cm predefined skin areas on the ventral forearms during one of two study visits. The pre-treatment will occur under topical occlusion for 30 minutes to allow the ointment to be adsorbed. Following this, residual ointment will be removed and sensory testing, strictly within the pretreated area, will commence.

Treatment:

Combination Product: Ketamine hydrochloride, Amitriptyline hydrochloride, and Lidocaine hydrochloride

Topical ketamine

Experimental group

Description:

Topical ketamine 10% will be applied to one four 4 x 4 cm predefined skin areas on the ventral forearms during one of two study visits. The pre-treatment will occur under topical occlusion for 30 minutes to allow the ointment to be adsorbed. Following this, residual ointment will be removed and sensory testing, strictly within the pretreated area, will commence.

Treatment:

Drug: Ketamine Hydrochloride

Topical amitriptyline

Experimental group

Description:

Topical amitriptyline 5% will be applied to one four 4 x 4 cm predefined skin areas on the ventral forearms during one of two study visits. The pre-treatment will occur under topical occlusion for 30 minutes to allow the ointment to be adsorbed. Following this, residual ointment will be removed and sensory testing, strictly within the pretreated area, will commence.

Treatment:

Drug: Amitriptyline Hydrochloride

Topical lidocaine

Experimental group

Description:

Topical lidocaine 5% will be applied to one four 4 x 4 cm predefined skin areas on the ventral forearms during one of two study visits. The pre-treatment will occur under topical occlusion for 30 minutes to allow the ointment to be adsorbed. Following this, residual ointment will be removed and sensory testing, strictly within the pretreated area, will commence.

Treatment:

Drug: Lidocaine Hydrochloride

Topical vehicle

Placebo Comparator group

Description:

Topical vehicle (PCCA Lipoderm) will be applied to one four 4 x 4 cm predefined skin areas on the ventral forearms during one of two study visits. The pre-treatment will occur under topical occlusion for 30 minutes to allow the ointment to be adsorbed. Following this, residual ointment will be removed and sensory testing, strictly within the pretreated area, will commence.

Treatment:

Drug: Lipoderm Cream