Immunologic Profile of Chronically Photodamaged Skin

NCT02889159 | Completed Phase 1 FDA Drug

• 1 other identifier: HUM00111845 / Derm 681
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Chronically photodamaged skin is visually characterized by dryness, wrinkles, brown spots, leathery appearance, etc. This happens as a result of excessive exposure to UV light from the sun. While the sun's exposure leaves the skin's surface visibly changed, the skin's unseen immune system may also be permanently altered as a result of the exposure, making it more likely to develop a variety of skin cancers and infections. This study will examine the lasting changes in the immune system of the skin caused by UV exposure. Investigators will stimulate different aspects of the skin's immune system by giving an injection of Candida Albicans (CANDIN®) and histamine phosphate (HISTATROL®), topical applications of imiquimod 5% cream (ALDARA®) and performing a tape stripping procedure with adhesive tape. The use of Candida Albicans (CANDIN®), histamine phosphate (HISTATROL®), and tape stripping are common procedures in clinical settings to stimulate skin desired skin responses. Imiquimod 5% cream (ALDARA®) is an FDA-approved drug for the treatment of basal cell carcinomas, actinic keratoses and genital warts. Investigators will compare the reaction of the skin's immune system on a cellular level from skin normally exposed to the sun exposure to an area normally hidden from sun exposure.

Conditions

Photoaged Skin; Normal Skin

Keywords

photoaging

Outcome Measures

Primary Outcomes (3)

• Erythema in photodamaged and photoprotected skin

  Measured via the a\* output value on the Chroma Meter at baseline visit/visit 1, visit 2 (visit 1 + 48 hours +/- 12 hours) and visit 3 (visit 1 + 96 hours +/- 12 hours).

  5 days

• Human Beta Defensin 2 (DEFB4) Fold Change

  DEFB4 will be measured in absolute units expressed as a fold change compared to the control using skin biopsy specimens obtained at visits baseline visit/visit 1 (n=2), visit 2 (visit 1 + 48 hours +/- 12 hours) (n=6), and visit 3 (visit 1 + 96 hours +/- 12 hours) (n=2).

  5 days

• Wheal Response in photodamaged and photoprotected skin

  Measured in millimeters (mm) with standardized induration measurements at baseline visit/visit 1 and visit 2 (visit 1 + 48 hours +/- 12 hours).

  5 days

Study Arms (5)

Candida albicans antigen

OTHER

useful in measuring the capacity of a person to manifest a delayed-type hypersensitivity response

Biological: Candida albicans antigen

histamine phosphate

OTHER

useful to assess type I IgE-mediated hypersensitivity reactions

Biological: histamine phosphate

imiquimod 5% cream

OTHER

direct stimulator of TLR-7, a key component of the innate immune response with downstream signaling effects involving the adaptive immune response

Biological: imiquimod 5% cream

tape stripping

OTHER

to create alterations in key inflammatory mediators involved in both the innate and adaptive immune responses

Procedure: Tape Stripping

Control

NO INTERVENTION

control sample from both sun exposed and non-sun exposed skin

Interventions

Candida albicans antigen BIOLOGICAL

0.1 milliliter (mL) injection into superficial dermis making small bleb at Baseline Visit.

Also known as: CANDIN

Candida albicans antigen

histamine phosphate BIOLOGICAL

0.01 milliliter (mL) of histamine phosphate injected into the superficial dermis making a small bleb at Baseline Visit.

Also known as: HISTATROL

histamine phosphate

imiquimod 5% cream BIOLOGICAL

Pea sized amount of 5% cream to be applied to designated areas once daily for 4 days, beginning at Baseline Visit.

Also known as: ALDARA

imiquimod 5% cream

Tape Stripping PROCEDURE

At Baseline Visit, adhesive tape firmly applied to designated area for 2 seconds, then removed. Procedure repeated between 20 and 50 times until skin is slightly red and tacky.

tape stripping

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• Subject is at least 18 years of age
• Good general health
• No disease states, physical conditions or medications that would impair evaluation of the test sites
• Willingness and ability to follow protocol
• Signed, written, and witnessed informed consent form
• Subject to have either severe clinical photodamage or no clinical photodamage
• If female, subjects who are either of non-childbearing potential (defined as post-menopausal-absence of menstrual bleeding for 1 year - or as having undergone bilateral tubal ligation, hysterectomy or bilateral oophorectomy), or, if of childbearing potential, subjects who have had a negative urine pregnancy test at the beginning of the study, and have agreed to practice appropriate birth control to prevent pregnancy during the study. The type and dose of birth control must have been stable for at least 3 months prior to study entry and not be expected to change during the study.

You may not qualify if:

• Current tanning bed use or phototherapy
• Individuals who have lidocaine sensitivity
• Subjects with severe allergies manifested by a history of anaphylaxis, or history of presence of multiple severe allergies
• Subjects with a history of asthma
• Subjects on topical or systemic antihistamine therapy
• Subjects on tricyclic antidepressant therapy
• Subjects on beta-blocker medications
• Subjects on any immunosuppressive therapy
• Subjects with active inflammation or infection on the skin
• Subjects with a history of connective tissues diseases including rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis or systemic lupus erythematosus
• Subjects with a history of inflammatory or autoimmune skin disease (including atopic dermatitis, eczema, or psoriasis)
• Subjects with a history of abnormal blood counts within the past one year
• Subjects with a history of hypotension, severe hypertension, severe cardiac, pulmonary, or renal disease
• Subjects with a history of keloid formation or hypertrophic scarring
• Topical or systemic steroid use in the two weeks prior to study entry

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

University of Michigan Department of Dermatology

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Interventions

PRA1 protein, Candida albicans; histamine phosphate; Histamine; Imiquimod

Intervention Hierarchy (Ancestors)

Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Ethylamines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Autacoids; Inflammation Mediators; Biological Factors; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Yolanda Helfrich, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Program for Clinical Research In Dermatology

Study Record Dates

• First Submitted: June 6, 2016
• First Posted: September 5, 2016
• Study Start: June 6, 2016
• Primary Completion: February 9, 2023
• Study Completion: February 23, 2023
• Last Updated: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)