Pruritus
Conditions
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.
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).
Interventions
DRUGAcetaminophen
Topical acetaminophen gel
DRUGCarbomer 980
Topical vehicle gel
Sponsors
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topical Acetaminophen and Vehicle Gel 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 | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | Topical Acetaminophen and Vehicle Gel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 0 / 17 | 0 / 17 | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 0 / 17 | 0 / 17 |
Outcome results
Primary
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.
Time frame: 10 minutes
Population: All subjects received 4 topical cream treatments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topical 5% acetaminophen gel | Peak Itch Intensity Between the Vehicle and Active Treatments During Histaminergic Itch Induction | 2.04 Intensity score | Standard Deviation 2.52 |
| Topical 2.5% acetaminophen gel | Peak Itch Intensity Between the Vehicle and Active Treatments During Histaminergic Itch Induction | 2.38 Intensity score | Standard Deviation 2.26 |
| Topical 1% acetaminophen gel | Peak Itch Intensity Between the Vehicle and Active Treatments During Histaminergic Itch Induction | 2.91 Intensity score | Standard Deviation 2.31 |
| Topical vehicle gel | Peak Itch Intensity Between the Vehicle and Active Treatments During Histaminergic Itch Induction | 3.07 Intensity score | Standard Deviation 2.64 |
Primary
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.
Time frame: 10 minutes
Population: All subjects received 4 topical cream treatments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topical 5% acetaminophen gel | Peak Itch Intensity Between the Vehicle and Active Treatments During Non-histaminergic Itch Induction | 4.5 Intensity score | Standard Deviation 1.98 |
| Topical 2.5% acetaminophen gel | Peak Itch Intensity Between the Vehicle and Active Treatments During Non-histaminergic Itch Induction | 3.94 Intensity score | Standard Deviation 2.77 |
| Topical 1% acetaminophen gel | Peak Itch Intensity Between the Vehicle and Active Treatments During Non-histaminergic Itch Induction | 5.32 Intensity score | Standard Deviation 2.29 |
| Topical vehicle gel | Peak Itch Intensity Between the Vehicle and Active Treatments During Non-histaminergic Itch Induction | 5.79 Intensity score | Standard Deviation 2.61 |
Secondary
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.
Time frame: 3 minutes
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Topical 5% acetaminophen gel | Thermal Threshold Detection (Heat Pain) | After histamine itch induction | 43.95 Degrees celsius | Standard Deviation 2.17 |
| Topical 5% acetaminophen gel | Thermal Threshold Detection (Heat Pain) | After non-histamine itch induction | 43.99 Degrees celsius | Standard Deviation 0.95 |
| Topical 2.5% acetaminophen gel | Thermal Threshold Detection (Heat Pain) | After non-histamine itch induction | 44.03 Degrees celsius | Standard Deviation 0.81 |
| Topical 2.5% acetaminophen gel | Thermal Threshold Detection (Heat Pain) | After histamine itch induction | 44.51 Degrees celsius | Standard Deviation 0.72 |
| Topical 1% acetaminophen gel | Thermal Threshold Detection (Heat Pain) | After histamine itch induction | 43.94 Degrees celsius | Standard Deviation 0.88 |
| Topical 1% acetaminophen gel | Thermal Threshold Detection (Heat Pain) | After non-histamine itch induction | 44.30 Degrees celsius | Standard Deviation 0.64 |
| Topical vehicle gel | Thermal Threshold Detection (Heat Pain) | After histamine itch induction | 44.07 Degrees celsius | Standard Deviation 0.56 |
| Topical vehicle gel | Thermal Threshold Detection (Heat Pain) | After non-histamine itch induction | 44.20 Degrees celsius | Standard Deviation 0.59 |