Thermosensitivity of a Topical Palmitated Formulation of Capsaicin

Study Overview
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Brief Summary
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This is a study of the effects of capsaicin, the ingredient that makes hot peppers hot. Capsaicin is currently used in topical ointments to provide temporary relief of minor aches and joint pain associated with arthritis, simple backache, strains, and sprains. This is a pilot research study that compares the potential of two different capsaicin creams to cause irritation or burning sensation when a small amount (about the size of a quarter) is applied to each forearm of a participant. The amount of capsaicin used in the creams is the same as those found in over-the-counter capsaicin products. The test creams are experimental.

Detailed Description
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The study design will detect levels of patient dysesthesia in response to Capsadyn using a three-arm, group comparison. Capsadyn will be compared to an active control, capsaicin alone (Cap), and to placebo, cream alone (PL). The design will use a double-blind for assignment of test article to the three arms. Both the test article administrator and patient will be blinded to test article identity. The test article will be packaged in a coded, white-label, jar with cotton swab applicator. Subjects. Subjects for the clinical trial will be recruited through the Carilion Clinic Dermatology Department in Roanoke, VA. In order to minimize the skin area exposed to capsaicin, test articles will be administered to about an 8 cm2 area of the volar forearm. Subject will be informed of the possibility of a transient capsaicin-induced burning sensation along with redness. Study Groups. The groups are designated Pal and Cap or PL, a placebo (PL) group. The capsaicin drugs are topical analgesics for the temporary relief of minor aches and pains of muscles and joints associated with arthritis. Pal is 0.25% palmitated capsaicin. Cap is 0.25% capsaicin alone and is an active comparator. PL is vehicle alone. Test articles will be balanced arm-to-arm by Pal/Cap, Pal/PL, Cap/PL. Pretest baseline scores will be compared to treatment scores by one-way ANOVA followed by post-hoc analyses for Pal vs PL, Pal vs Cap and Cap vs PL. An active comparator is used since non-palmitated capsaicin (unprotected) produces heat. The sensory stimuli would break a neutral control such as vehicle alone. Cap is used since it can be formulated to match a commercially-available topical capsaicin analgesic sold over-the counter (PainBloc24) at 0.25% concentration. This balances the same concentration of Capsadyn. The 0.25% concentration is based on the upper-limit concentration for capsaicin as specified by the FDA Tentative Final Monograph. A PL group is included since the placebo effect has to be assumed to be intrinsic to pharmaceutical intervention studies. If a placebo effect occurs that would interfere with assessment of the test article intervention, then those assessments can be evaluated with respect to the placebo group.

Official Title
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A Double-Blind, Randomized, Pilot Study to Investigate the Thermosensitivity of a Topical Palmitated Formulation of Capsaicin

Conditions
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Pain Management

Intervention / Treatment
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* Drug: Capsaicin 0.025% Cream
* Drug: Capsaicin Palmitate
* Drug: Placebo Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 35 to 75 years of age Has two arms Has intact, unscarred skin over forearms Absence of any eczema, hyperkeratosis, scleroderma or other dermatological conditions afflicting the area of test article application that may interfere with absorption as determined by the PI. Must agree to not wash forearms during the study period unless a highly uncomfortable burning sensitivity occurs. Must be willing to use treatments blinded. Must be willing and able to comply with protocol requirements for the duration of study participation, including answering VAS queries in good faith and as diligently as possible. Exclusion Criteria: Younger than 35 and older than 75 years of age No previous use of capsaicin products for 48 hours prior to time 0 (application) of test articles. Any dermatological conditions that in the judgement of the study site investigator has the potential to disrupt skin integrity or alter sensory function on the forearms. Any skin infection, skin irritation (e.g. poison oak), history of eczema, trauma or burn (including sunburn) on the forearms within 30 days preceding application of test article. Any recent medical history of painful conditions, surgery, or injury involving or affecting the forearms that may impede skin sensitivity. Use of any topically applied products at any location, including prescription or over-the-counter (OTC) analgesic creams/lotions/patches, non-steroidal anti-inflammatory drugs, counter-irritants, local anesthetics, steroids 24 hours prior to the application visit. History or current substance abuse including alcoholism/alcohol abuse, as judged by the study site investigator. History of hypersensitivity to capsaicin (i.e. chili peppers or OTC capsaicin products). At least 30 days since prior topical medications to the skin of the forearms except for emollients or sunscreens. No concurrent therapy that may interfere with clinical evaluations. No concurrent enrollment in another clinical trial.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Each subject will be given two of either: vehicle cream containing 0.25% capsaicin palmitate vehicle cream containing 0.25% non-palmitated capsaicin vehicle cream alone (placebo)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capsaicin Palmitate<br>Vehicle cream containing 0.25% capsaicin palmitate will be applied to an 8 cm2 area of skin on the subject's forearm | Drug: Capsaicin 0.025% Cream<br>* A small amount of cream about the size of a U.S. half dollar containing 0.25% non-palmitated capsaicin will be applied to participant's forearm using gloved fingers with visible cream left on the surface for one hour.<br>Drug: Placebo Cream<br>* A small amount of topical cream about the size of a U.S. half dollar will be applied to participant's forearm using gloved fingers with visible cream left on the surface for one hour.<br>|
| Active Comparator: Non-Palmitated Capsaicin<br>Vehicle cream containing 0.25% non-palmitated capsaicin will be applied to an 8 cm2 area of skin on the subject's forearm | Drug: Capsaicin Palmitate<br>* A small amount of cream about the size of a U.S. half dollar containing 0.25% capsaicin palmitate will be applied to participant's forearm using gloved fingers with visible cream left on the surface for one hour.<br>* Other names: Capsadyn;Drug: Placebo Cream<br>* A small amount of topical cream about the size of a U.S. half dollar will be applied to participant's forearm using gloved fingers with visible cream left on the surface for one hour.<br>|
| Placebo Comparator: Vehicle Cream<br>Vehicle cream placebo will be applied to an 8 cm2 area of skin on the subject's forearm | Drug: Capsaicin 0.025% Cream<br>* A small amount of cream about the size of a U.S. half dollar containing 0.25% non-palmitated capsaicin will be applied to participant's forearm using gloved fingers with visible cream left on the surface for one hour.<br>Drug: Capsaicin Palmitate<br>* A small amount of cream about the size of a U.S. half dollar containing 0.25% capsaicin palmitate will be applied to participant's forearm using gloved fingers with visible cream left on the surface for one hour.<br>* Other names: Capsadyn;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine any change in relative burning potential for capsaicin palmitate in comparison to non-palmitated capsaicin and to placebo. | Subject assessment of any changes in the presence of a burn using a VAS scale 0 to 100 for both areas of the forearms where topical cream was applied. | Assess for changes every 10 minutes after application for one hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the presence and time course of erythema. | The presence of erythema will be noted and qualified by a clinician erythema assessment scale. | Assessed every 10 minutes after application for one hour | 
| Determine the presence and time course of skin irritation | Subjects will be asked to assess any tingling, burning, soothing, freezing, and itching of the skin in the area where the topical cream was applied. | Assessed every 10 minutes after application for one hour |