Thermosensitivity of a Topical Palmitated Formulation of Capsaicin

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

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.

Study Overview

• Status: Completed
• Conditions: Pain Management
• Intervention / Treatment: Drug: Capsaicin 0.1% Cream; Drug: Placebo Cream; Drug: Capsaicin Palmitate 0.25% Cream

Detailed Description

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 a 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.

Participants. Participants 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 0.10% 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. Zostrix at 0.1% capsaicin was used as the active comparator (Cap), a commercially-available topical capsaicin analgesic sold over-the-counter. The concentration of 0.25% capsaicin for Capsadyn (Pal), was 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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Sarah Bodoh; Phone Number: 800-422-8482; Email: research@carilionclinic.org
• Study Contact Backup: Name: Kristina Cooper; Phone Number: 800-422-8482; Email: research@carilionclinic.org

Study Locations

• United States
  • Virginia
    • Roanoke, Virginia, United States, 24016
      • Carilion Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 33 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capsaicin Palmitate; Cream containing 0.25% capsaicin palmitate will be applied to an 8 cm2 area of skin on the subject's forearm	Drug: Capsaicin 0.1% Cream; A small amount of cream about the size of a U.S. quarter containing 0.10% non-palmitated capsaicin will be applied to participant's forearm using gloved fingers with visible cream left on the surface for one hour.; Other Names: Zostrix; Drug: Placebo Cream; A small amount of cream about the size of a U.S. quarter will be applied to participant's forearm using gloved fingers with visible cream left on the surface for one hour.
Active Comparator: Capsaicin; Cream containing 0.1% capsaicin will be applied to an 8 cm2 area of skin on the subject's forearm	Drug: Placebo Cream; A small amount of cream about the size of a U.S. quarter will be applied to participant's forearm using gloved fingers with visible cream left on the surface for one hour.; Drug: Capsaicin Palmitate 0.25% Cream; A small amount of cream about the size of a U.S. quarter 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.; Other Names: Capsadyn
Placebo Comparator: Placebo Cream; Placebo cream will be applied to an 8 cm2 area of skin on the subject's forearm	Drug: Capsaicin 0.1% Cream; A small amount of cream about the size of a U.S. quarter containing 0.10% non-palmitated capsaicin will be applied to participant's forearm using gloved fingers with visible cream left on the surface for one hour.; Other Names: Zostrix; Drug: Capsaicin Palmitate 0.25% Cream; A small amount of cream about the size of a U.S. quarter 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.; Other Names: Capsadyn

What is the study measuring?

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 10 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 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
Determine the presence and time course of erythema.	The presence of erythema will be noted and qualified by a clinician erythema assessment scale of 1-4 with 1 being almost clear of redness and 4 being severe redness.	Assessed every 10 minutes after application for one hour

Collaborators and Investigators

• Sponsor: Carilion Clinic
• Collaborators: Chorda Pharma, Inc.
• Investigators: Principal Investigator: Zachary Holcomb, MD, Carilion Clinic

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2022
• Primary Completion (Actual): January 11, 2024
• Study Completion (Actual): January 11, 2024

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: December 9, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Dermatologic Agents; Antipruritics; Capsaicin
• Other Study ID Numbers: IRB-21-1214

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be made available to investigative parties in publication format after study analysis is complete which will include de-identified participant data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes