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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

Tracking Information
First Submitted Date  ICMJE March 16, 2017
First Posted Date  ICMJE March 30, 2017
Results First Submitted Date  ICMJE February 19, 2019
Results First Posted Date  ICMJE July 2, 2019
Last Update Posted Date July 2, 2019
Actual Study Start Date  ICMJE May 23, 2017
Actual Primary Completion Date July 19, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
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".
Original Primary Outcome Measures  ICMJE
 (submitted: March 24, 2017)
The primary outcome is itch reduction (AUC) between the vehicle and active treatments (individual and KeAmLi-combo). [ Time Frame: 1 week ]
The primary outcome is the overall itch reduction (AUC) between the vehicle and 4 other active treatments (individual ketamine, amitriptyline, or lidocaine, and KeAmLi-combo).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2017)
  • A secondary outcome is any change in thermal thresholds (warmth and heat pain) between the vehicle and the active treatments. [ Time Frame: 1 week ]
    A secondary outcome is any change (measured in celsius) to the warmth and heat pain thermal thresholds for the topically applied ketamine, amitriptyline, lidocaine, and KeAmLi-combo by using controlled thermal stimuli.
  • A secondary outcome is any change in mechanical thresholds (mechanical detection and pain) between the vehicle and the active treatments. [ Time Frame: 1 week ]
    A secondary outcome is any change (measured in force mN) to the mechanical detection and pain thermal thresholds for the topically applied ketamine, amitriptyline, lidocaine, and KeAmLi-combo by using controlled mechanical stimuli.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine
Official Title  ICMJE Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Pruritus
Intervention  ICMJE
  • 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
  • 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
  • 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
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Combination Product: Ketamine hydrochloride, Amitriptyline hydrochloride, and Lidocaine hydrochloride
  • 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.
    Intervention: Drug: Ketamine Hydrochloride
  • 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.
    Intervention: Drug: Amitriptyline Hydrochloride
  • 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.
    Intervention: Drug: Lidocaine Hydrochloride
  • 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.
    Intervention: Drug: Lipoderm Cream
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 23, 2017)
13
Original Estimated Enrollment  ICMJE
 (submitted: March 24, 2017)
36
Actual Study Completion Date  ICMJE July 21, 2017
Actual Primary Completion Date July 19, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03096444
Other Study ID Numbers  ICMJE 20170087
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Gil Yosipovitch, University of Miami
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Gil Yosipovitch
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gil Yosipovitch, MD University of Miami
PRS Account University of Miami
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP