Topical Acetaminophen for Itch Relief: a Proof of Concept Study in Healthy Subjects
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
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:
|
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:
|
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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".
- 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
- 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
Inclusion Criteria:
-
Healthy subjects must be between 18 and 50 years of age.
-
Must be in general good health with no disease or physical conditions that would impair evaluation of itch and pain perception.
-
No history of chronic itch or pain.
-
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.
-
Must abstain from the use of moisturizers on the arms 24 hours before study visits.
Exclusion Criteria:
-
Individuals under 18 or over 50 years of age.
-
Inability to complete the required measures.
-
The presence of an itchy skin disease.
-
Diagnosis of diseased that would affect itch or pain perception (e.g. neuropathies).
-
Currently enrolled in any investigational study in which the subject is receiving any type of drug, biological, or non-drug therapy.
-
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.).
-
Use of emollients on the arms a week prior to the study and throughout the study.
-
Known allergies to acetaminophen and cowhage.
-
Pregnant women. (Women of child bearing potential will undergo an hCG pregnancy test).
-
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.- 20190133
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
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)
|
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)
|
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
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 |
Lxn202@med.miami.edu |
- 20190133