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Immunologic Profile of Chronically Photodamaged Skin

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ClinicalTrials.gov Identifier: NCT02889159
Recruitment Status : Recruiting
First Posted : September 5, 2016
Last Update Posted : May 20, 2019
Sponsor:
Information provided by (Responsible Party):
Yolanda Rosi Helfrich, University of Michigan

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.

Condition or disease Intervention/treatment Phase
Photoaged Skin Normal Skin Biological: Candida albicans antigen Biological: histamine phosphate Biological: imiquimod 5% cream Procedure: Tape Stripping Not Applicable

Detailed Description:

Chronically photodamaged skin is visually characterized by dryness, wrinkles, brown spots, leathery appearance, etc. While photodamage 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 aim to evaluate the lasting changes that lifetime UV exposure causes to the different components of the skin's immune system in chronically sun damaged skin (forearms) compared to sun-protected skin (buttocks). Investigators will compare the cellular responses to stimulation of the skin's innate immune system, the skin's adaptive immune system, and the skin's hypersensitivity responses between these two sites.

In order to stimulate the different arms of the immune system, investigators will be using the following interventions: an intradermal injection of Candida Albicans antigen, an intradermal injection of histamine phosphate, a topical application of imiquimod 5% cream, and a tape stripping procedure with adhesive tape. Skin testing with the C. albicans antigen is a useful procedure for measuring the capacity of a person to manifest a delayed-type hypersensitivity response and is commonly used in clinical settings to evaluate cellular immunity. Similarly, histamine phosphate is frequently used as a positive control in clinical tests to assess type I Immunoglobulin E (IgE)-mediated hypersensitivity reactions. Imiquimod 5% cream is a direct stimulator of toll-like receptor (TLR) 7, a key component of the innate immune response with downstream signaling effects involving the adaptive immune response. It is FDA-approved for the treatment superficial basal cell carcinomas, actinic keratoses, and genital warts. Finally, tape stripping is a validated procedure used to remove superficial layers of the epidermis in clinical study environments.

Objective: This is a mechanism of action pilot study designed to characterize the molecular nature of the local innate and adaptive immune response in chronically photodamaged skin (forearm) as compared to photoprotected skin (buttocks) using non-photodamaged individuals (forearms and buttocks) as a control.

Population: Adult subjects with or without photodamage will be entered into the study at the University of Michigan.

Procedures: study interventions (tape stripping, candida albicans and histamine phosphate injections, imiquimod 5% cream application), photography, Chroma Meter reading, biopsies, skin assessment


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Immunologic Profile of Chronically Photodamaged Skin
Actual Study Start Date : June 6, 2016
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Candida albicans antigen
useful in measuring the capacity of a person to manifest a delayed-type hypersensitivity response
Biological: Candida albicans antigen
0.1 milliliter (mL) injection into superficial dermis making small bleb at Baseline Visit.
Other Name: CANDIN

histamine phosphate
useful to assess type I IgE-mediated hypersensitivity reactions
Biological: histamine phosphate
0.01 milliliter (mL) of histamine phosphate injected into the superficial dermis making a small bleb at Baseline Visit.
Other Name: HISTATROL

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

tape stripping
to create alterations in key inflammatory mediators involved in both the innate and adaptive immune responses
Procedure: Tape Stripping
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.

No Intervention: Control
control sample from both sun exposed and non-sun exposed skin



Primary Outcome Measures :
  1. Erythema in photodamaged and photoprotected skin [ Time Frame: 5 days ]
    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).

  2. Human Beta Defensin 2 (DEFB4) Fold Change [ Time Frame: 5 days ]
    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).

  3. Wheal Response in photodamaged and photoprotected skin [ Time Frame: 5 days ]
    Measured in millimeters (mm) with standardized induration measurements at baseline visit/visit 1 and visit 2 (visit 1 + 48 hours +/- 12 hours).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • Antibiotic use in the two weeks prior to study entry or during the study
  • Has received an experimental drug or used an experimental device in the two weeks prior to study entry
  • Females who are pregnant or planning to become pregnant
  • Nursing females
  • Any other treatments that at the Investigator's judgment is likely to interfere with the study evaluation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02889159


Contacts
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Contact: Jennifer Bell 734-936-4075 jennbell@med.umich.edu
Contact: Bethany Ruffino 734-763-8076 bruffino@med.umich.edu

Locations
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United States, Michigan
University of Michigan Department of Dermatology Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Jennifer Bell    734-936-4075    jennbell@med.umich.edu   
Contact: Bethany Ruffino    734-763-8076    bruffino@med.umich.edu   
Sponsors and Collaborators
University of Michigan
Investigators
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Principal Investigator: Yolanda Helfrich, MD University of Michigan

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Responsible Party: Yolanda Rosi Helfrich, Director Program for Clinical Research In Dermatology, University of Michigan
ClinicalTrials.gov Identifier: NCT02889159     History of Changes
Other Study ID Numbers: HUM00111845 / Derm 681
First Posted: September 5, 2016    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yolanda Rosi Helfrich, University of Michigan:
photoaging
Additional relevant MeSH terms:
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Histamine
Histamine phosphate
Histamine Agonists
Histamine Agents
Imiquimod
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Interferon Inducers
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action