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Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine

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ClinicalTrials.gov Identifier: NCT03096444
Recruitment Status : Terminated (Efficacy was not seen after interim analysis)
First Posted : March 30, 2017
Results First Posted : July 2, 2019
Last Update Posted : July 2, 2019
Sponsor:
Information provided by (Responsible Party):
Gil Yosipovitch, University of Miami

Study Description
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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.

Condition or disease Intervention/treatment Phase
Pruritus Drug: Ketamine Hydrochloride Drug: Amitriptyline Hydrochloride Drug: Lidocaine Hydrochloride Combination Product: Ketamine hydrochloride, Amitriptyline hydrochloride, and Lidocaine hydrochloride Drug: Lipoderm Cream Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine
Actual Study Start Date : May 23, 2017
Actual Primary Completion Date : July 19, 2017
Actual Study Completion Date : July 21, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Itching

Arms and Interventions
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Arm Intervention/treatment
Experimental: Topical KeAmLi combo
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.
 Combination Product: Ketamine hydrochloride, Amitriptyline hydrochloride, and Lidocaine hydrochloride
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.
Other Name: Topical KeAmLi combo
Experimental: Topical ketamine
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.
 Drug: Ketamine Hydrochloride
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.
Other Name: Topical ketamine
Experimental: Topical amitriptyline
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.
 Drug: Amitriptyline Hydrochloride
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.
Other Name: Topical amitriptyline
Experimental: Topical lidocaine
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.
 Drug: Lidocaine Hydrochloride
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.
Other Name: Topical lidocaine
Placebo Comparator: Topical vehicle
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.
 Drug: Lipoderm Cream
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.
Other Name: Topical vehicle


Outcome Measures
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Primary Outcome Measures :
  1. Peak Itch Intensity Between the Vehicle and Active Treatments (Individual and KeAmLi-combo). [ Time Frame: 10 minutes ]
    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".


Secondary Outcome Measures :
  1. Thermal Threshold Detection (Warmth and Heat Pain) [ Time Frame: 3 minutes ]
    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.

  2. Mechanical Thresholds (Mechanical Detection and Pain). [ Time Frame: 5 minutes ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03096444


Locations
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United States, Florida
University of Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
Gil Yosipovitch
Investigators
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Principal Investigator: Gil Yosipovitch, MD University of Miami
  Study Documents (Full-Text)

Documents provided by Gil Yosipovitch, University of Miami:
Study Protocol and Statistical Analysis Plan  [PDF] March 29, 2017

More Information
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Publications:

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Responsible Party: Gil Yosipovitch, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT03096444    
Other Study ID Numbers: 20170087
First Posted: March 30, 2017    Key Record Dates
Results First Posted: July 2, 2019
Last Update Posted: July 2, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pruritus
Skin Diseases
Skin Manifestations
Lidocaine
Ketamine
Amitriptyline
Amitriptyline, perphenazine drug combination
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
 Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Analgesics
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Analgesics, Non-Narcotic
Adrenergic Uptake Inhibitors