Topical Acetaminophen for Itch Relief: a Proof of Concept Study in Healthy Subjects

Sponsor
University of Miami (Other)
Overall Status
Completed
CT.gov ID
NCT03997851
Collaborator
(none)
17
1
4
7.9
2.2

Study Details

Study Description

Brief Summary

Currently, topical antihistamines and corticosteroids are mainly used for itching relief. However, the over the counter antihistamines are not effective on all itch conditions. Acetaminophen is a popular and widely used OTC drug for pain relief. Although its mode of action is still unknown, recent studies have shown that acetaminophen indirectly activates cannabinoid CB1 receptors. Recent studies have shown that topical cannabinoid agonists are effective for itch relief, the efficacy of topical acetaminophen will be tested for non-histaminergic itch relief.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

This will be a single-blinded, vehicle-controlled randomized study in healthy controls to test the efficacy of the topical gel formulation with three differing concentrations of acetaminophen (APAP) for itch relief. To detect medium effects of the treatments with a given α of 0.5 and an error probability of 0.05, with a power of 0.95, the number of participants needed is 36 (10 within post hoc pairwise comparisons).

Study Design

Study Type:
Interventional
Actual Enrollment :
17 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
The antipruritic effect of 3 topical treatments of varying doses and 1 vehicle treatment will be explored in each subject. One study visit will consist of testing all topical formulations on histaminergic induced itch, and second study visit will test all topical formulations on non-histaminergic induced itch.The antipruritic effect of 3 topical treatments of varying doses and 1 vehicle treatment will be explored in each subject. One study visit will consist of testing all topical formulations on histaminergic induced itch, and second study visit will test all topical formulations on non-histaminergic induced itch.
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Topical Acetaminophen for Itch Relief: a Proof of Concept Study in Healthy Subjects
Actual Study Start Date :
Jul 22, 2019
Actual Primary Completion Date :
Mar 18, 2020
Actual Study Completion Date :
Mar 18, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Topical 5% acetaminophen gel

Topical 5% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area.

Drug: Acetaminophen
Topical acetaminophen gel
Other Names:
  • Topical acetaminophen gel
  • Experimental: Topical 2.5% acetaminophen gel

    Topical 2.5% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area.

    Drug: Acetaminophen
    Topical acetaminophen gel
    Other Names:
  • Topical acetaminophen gel
  • Experimental: Topical 1% acetaminophen gel

    Topical 1% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area.

    Drug: Acetaminophen
    Topical acetaminophen gel
    Other Names:
  • Topical acetaminophen gel
  • Placebo Comparator: Topical vehicle gel

    Topical vehile gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area.

    Drug: Carbomer 980
    Topical vehicle gel
    Other Names:
  • Topical vehicle gel
  • Outcome Measures

    Primary Outcome Measures

    1. Peak Itch Intensity Between the Vehicle and Active Treatments During Non-histaminergic Itch Induction [10 minutes]

      Peak itch intensity between the vehicle and 3 other active treatments (5%, 2.5%, and 1% acetaminophen gels) after non-histaminergic itch induction (cowhage). Itch intensity was measured on a 10cm scale visual analog scale for 10 minutes. 0 was weighted with "no itch" and 10 was weighted with "most itch imaginable".

    2. Peak Itch Intensity Between the Vehicle and Active Treatments During Histaminergic Itch Induction [10 minutes]

      Peak itch intensity between the vehicle and 3 other active treatments (5%, 2.5%, and 1% acetaminophen gels) after histaminergic itch induction. Itch intensity was measured on a 10cm scale visual analog scale for 10 minutes. 0 was weighted with "no itch" and 10 was weighted with "most itch imaginable".

    Secondary Outcome Measures

    1. Thermal Threshold Detection (Heat Pain) [3 minutes]

      Standardized quantitative sensory testing is performed to measure heat pain threshold (assesses the threshold at which heat pain sensation is first detected). Measured in Celsius.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    1. Healthy subjects must be 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 from the week prior to the study till the completion of the study.

    5. Must abstain from the use of moisturizers on the arms 24 hours before study visits.

    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.

    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 in the week prior to the study and throughout the study (e.g. antihistamines, anesthetics, opioids, neuroleptics, etc.).

    7. Use of emollients on the arms a week prior to the study and throughout the study.

    8. Known allergies to acetaminophen and cowhage.

    9. Pregnant women. (Women of child bearing potential will undergo an hCG pregnancy test).

    10. Currently incarcerated.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Miami Miami Florida United States 33136

    Sponsors and Collaborators

    • University of Miami

    Investigators

    • Principal Investigator: Gil Yosipovitch, MD, University of Miami

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Gil Yosipovitch, Professor, University of Miami
    ClinicalTrials.gov Identifier:
    NCT03997851
    Other Study ID Numbers:
    • 20190133
    First Posted:
    Jun 25, 2019
    Last Update Posted:
    Apr 19, 2021
    Last Verified:
    Jun 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Topical Acetaminophen and Vehicle Gel
    Arm/Group Description Each participant will receive topical gel treatments applied for 30 minutes to 4 separate 4 x 4 cm predefined skin areas on the ventral forearms twice at 2 separate study visits. The 4 treatments are: 5% acetaminophen gel 2.5% acetaminophen gel 1% acetaminophen gel Vehicle gel Acetaminophen: Topical acetaminophen gel
    Period Title: Overall Study
    STARTED 17
    COMPLETED 17
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Topical Acetaminophen and Vehicle Gel
    Arm/Group Description Each participant will receive topical gel treatments applied for 30 minutes to 4 separate 4 x 4 cm predefined skin areas on the ventral forearms twice at 2 separate study visits. The 4 treatments are: 5% acetaminophen gel 2.5% acetaminophen gel 1% acetaminophen gel Vehicle gel Acetaminophen: Topical acetaminophen gel
    Overall Participants 17
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    17
    100%
    >=65 years
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    15
    88.2%
    Male
    2
    11.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    5
    29.4%
    Not Hispanic or Latino
    12
    70.6%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    3
    17.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    3
    17.6%
    White
    11
    64.7%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Peak Itch Intensity Between the Vehicle and Active Treatments During Non-histaminergic Itch Induction
    Description Peak itch intensity between the vehicle and 3 other active treatments (5%, 2.5%, and 1% acetaminophen gels) after non-histaminergic itch induction (cowhage). Itch intensity was measured on a 10cm scale visual analog scale for 10 minutes. 0 was weighted with "no itch" and 10 was weighted with "most itch imaginable".
    Time Frame 10 minutes

    Outcome Measure Data

    Analysis Population Description
    All subjects received 4 topical cream treatments.
    Arm/Group Title Topical 5% Acetaminophen Gel Topical 2.5% Acetaminophen Gel Topical 1% Acetaminophen Gel Topical Vehicle Gel
    Arm/Group Description Topical 5% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical 2.5% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical 1% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical vehile gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Carbomer 980: Topical vehicle gel
    Measure Participants 17 17 17 17
    Mean (Standard Deviation) [Intensity score]
    4.5
    (1.98)
    3.94
    (2.77)
    5.32
    (2.29)
    5.79
    (2.61)
    2. Primary Outcome
    Title Peak Itch Intensity Between the Vehicle and Active Treatments During Histaminergic Itch Induction
    Description Peak itch intensity between the vehicle and 3 other active treatments (5%, 2.5%, and 1% acetaminophen gels) after histaminergic itch induction. Itch intensity was measured on a 10cm scale visual analog scale for 10 minutes. 0 was weighted with "no itch" and 10 was weighted with "most itch imaginable".
    Time Frame 10 minutes

    Outcome Measure Data

    Analysis Population Description
    All subjects received 4 topical cream treatments.
    Arm/Group Title Topical 5% Acetaminophen Gel Topical 2.5% Acetaminophen Gel Topical 1% Acetaminophen Gel Topical Vehicle Gel
    Arm/Group Description Topical 5% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical 2.5% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical 1% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical vehile gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Carbomer 980: Topical vehicle gel
    Measure Participants 17 17 17 17
    Mean (Standard Deviation) [Intensity score]
    2.04
    (2.52)
    2.38
    (2.26)
    2.91
    (2.31)
    3.07
    (2.64)
    3. Secondary Outcome
    Title Thermal Threshold Detection (Heat Pain)
    Description Standardized quantitative sensory testing is performed to measure heat pain threshold (assesses the threshold at which heat pain sensation is first detected). Measured in Celsius.
    Time Frame 3 minutes

    Outcome Measure Data

    Analysis Population Description
    All subjects received treatment with the 4 topical cream formulations at 2 study visits. Quantitative sensory testing was performed on each area of treated skin.
    Arm/Group Title Topical 5% Acetaminophen Gel Topical 2.5% Acetaminophen Gel Topical 1% Acetaminophen Gel Topical Vehicle Gel
    Arm/Group Description Topical 5% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical 2.5% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical 1% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical vehile gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Carbomer 980: Topical vehicle gel
    Measure Participants 17 17 17 17
    After histamine itch induction
    43.95
    (2.17)
    44.51
    (0.72)
    43.94
    (0.88)
    44.07
    (0.56)
    After non-histamine itch induction
    43.99
    (0.95)
    44.03
    (0.81)
    44.30
    (0.64)
    44.20
    (0.59)

    Adverse Events

    Time Frame Up to 2 weeks.
    Adverse Event Reporting Description
    Arm/Group Title Topical 5% Acetaminophen Gel Topical 2.5% Acetaminophen Gel Topical 1% Acetaminophen Gel Topical Vehicle Gel
    Arm/Group Description Topical 5% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical 2.5% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical 1% acetaminophen gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Acetaminophen: Topical acetaminophen gel Topical vehile gel will be applied to one 4x4 cm predefined skin area on the ventral forearm during 2 study visits. The gel will be applied to the test area and will be allowed 30 minutes to adsorb. Following this pre-treatment, residual gel will be removed and itch induction/sensory testing will commence, strictly within the pre-treated area. Carbomer 980: Topical vehicle gel
    All Cause Mortality
    Topical 5% Acetaminophen Gel Topical 2.5% Acetaminophen Gel Topical 1% Acetaminophen Gel Topical Vehicle Gel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/17 (0%) 0/17 (0%) 0/17 (0%) 0/17 (0%)
    Serious Adverse Events
    Topical 5% Acetaminophen Gel Topical 2.5% Acetaminophen Gel Topical 1% Acetaminophen Gel Topical Vehicle Gel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/17 (0%) 0/17 (0%) 0/17 (0%) 0/17 (0%)
    Other (Not Including Serious) Adverse Events
    Topical 5% Acetaminophen Gel Topical 2.5% Acetaminophen Gel Topical 1% Acetaminophen Gel Topical Vehicle Gel
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/17 (0%) 0/17 (0%) 0/17 (0%) 0/17 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Leigh Nattkemper
    Organization University of Miami
    Phone 3055889734
    Email Lxn202@med.miami.edu
    Responsible Party:
    Gil Yosipovitch, Professor, University of Miami
    ClinicalTrials.gov Identifier:
    NCT03997851
    Other Study ID Numbers:
    • 20190133
    First Posted:
    Jun 25, 2019
    Last Update Posted:
    Apr 19, 2021
    Last Verified:
    Jun 1, 2020