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

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.

Study Overview

• Status: Completed
• Conditions: Pruritus
• Intervention / Treatment: Drug: Acetaminophen; Drug: Carbomer 980

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 Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Itch Intensity Between the Vehicle and Active Treatments During Non-histaminergic Itch Induction	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".	10 minutes
Peak Itch Intensity Between the Vehicle and Active Treatments During Histaminergic Itch Induction	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".	10 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thermal Threshold Detection (Heat Pain)	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.	3 minutes

Collaborators and Investigators

• Sponsor: University of Miami

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 22, 2019
• Primary Completion (ACTUAL): March 18, 2020
• Study Completion (ACTUAL): March 18, 2020

Study Registration Dates

• First Submitted: June 24, 2019
• First Submitted That Met QC Criteria: June 24, 2019
• First Posted (ACTUAL): June 25, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 19, 2021
• Last Update Submitted That Met QC Criteria: March 22, 2021
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 20190133

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No