Clinical trial NCT03096444: Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine
Official title: Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pruritus
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2017-03-30
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The antipruritic effect of 4 topical treatments and 1 vehicle treatment will be explored in each subject. Study visit 1 will consist of testing 3 topical formulations, and study visit 2 will test the remaining 2 topical formulations in each subject.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Peak Itch Intensity Between the Vehicle and Active Treatments (Individual and KeAmLi-combo).
timeFrame: 10 minutes
Secondary outcomes:
measure: Thermal Threshold Detection (Warmth and Heat Pain)
timeFrame: 3 minutes
measure: Mechanical Thresholds (Mechanical Detection and Pain).
timeFrame: 5 minutes
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Gil Yosipovitch, MD
role: PRINCIPAL_INVESTIGATOR
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