Official Title: “Mechanistically-Based Optimization of UV Radiation Therapy in Psoriasis”

The purpose of this study is 1) to determine whether Imiquimod or Steroid pretreatment modifies UVB laser light response resulting in increased cell death compared to UVB laser light alone; 2) to determine if pretreatment of psoriatic lesions with Imiquimod or Steroid prior to UVB laser light exposure selectively effects various T cell functions; 3) to determine clinical results from the Imiquimod/Steroid/UVB laser light and correlate those changes with immuno-histochemical changes in the skin; and 4) to determine if single high dose lesion limited UVB laser light intervention combined with Imiquimod or Steroid influences T cell changes

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Active Control, Crossover Assignment, Efficacy Study

The characteristic lesion of psoriasis is a sharply demarcated erythematous papule or plaque with excessive scaling due to hyperproliferating keratinocytes, infiltrating granulocytes, and a dense mononuclear infiltrate with activated T cells. To date, no one mechanism has been explanatory for the panoply of changes that occur in both the dermis and epidermis of psoriasis patients. Several key findings have shown that cutaneous T cells play a key role in the propagation of the disease; memory-type T cells home to the skin, specifically due to expression of cutaneous lymphocyte antigen (CLA), and are the main effector cells in psoriatic tissue responsible for the production of cytokines that result in exacerbated cutaneous inflammation. T cell recruitment is thought to occur in psoriasis, in part,as a result of cytokine and chemokine release from keratinocytes, macrophages, and endothelial cells. CLA-positive T cells migrate into the tissues where memory-effector T cells are activated and expand. This migration is critical to maintenance of the psoriasis lesions, because anti-LFA-1 antibodies (efalizumab) are effective in treating psoriasis, resulting in blood lymphocytosis and tissue depletion of T cells. Despite many years of using UVB phototherapy in the treatment of psoriasis, its mechanism of action is based mainly on in vitro exposures of isolated cells and on extrapolations from UV effects on normal skin, with little direct data from lesional skin.

Previously, our studies determined optimal single efficacious dose using the Excimer laser, refined the mechanism of UVB action in psoriasis, developed key cytokine quantitative meth -ods to assess targeted mRNA levels in psoriatic tissue after treatment, demonstrated that regulatory T cells from psoriasis tissue and blood appear to have a functional defect,and demon- strated that UVA component of solar radiation is a critical and significant contributor to UV-induced in vivo immuno-suppression. All of these previous findings lead us to our current hypothesis that direct selective apoptotic effects on the T mem/Teff cells may result in decreased APC activation and IL-12 over-riding of Treg suppression and a re-balanced Tre:Tmem/eff cell ratio which in turn may have a sustained remittive effect (high duration multi-month clearing of a psoriasis lesion after a single UVB laser light treatment.)

Intervention(s) in this Clinical Trial

• Drug: Imiquimod
• Drug: Clobetasol (glucosteroid)
• Device: Excimer laser (UVB light) treatment

Primary Measures

• T cell apoptosis

Secondary Measures

• Lesional Psoriasis Area and Assessment

Inclusion Criteria:

• The presence of plaque-type psoriasis in areas of the trunk, buttock, or extremities that are amenable to biopsy and evaluable disease in at least 2 cm² target treatment sites separated by ≥ 1 cm
• Age 21-70, both genders, all ethnicities
• No contraindications to phototherapy or biopsy procedures
• No topical steroid, tar, phototherapy, Vitamin D, or retinoid therapy to target lesions for at least 2 weeks prior to the study
• No systemic psoriasis therapy for at least four weeks prior to the study
• Able to give informed consent under IRB approval procedures

Exclusion Criteria:

• Photosensitivity disorders
• Active untreated diseases or medication usage which may interfere with UVB, wound healing, or immune function
• Hypersensitivity to both amide and esther anesthetics or epinephrine (keratome biopsies only)
• Inability to withdraw from aspirin or other anti-clotting agents for at least one week prior to the biopsies (keratome biopsies only)
• Inability to provide informed consent
• Pregnancy and /or lactating

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Department of Veterans Affairs

Overall Clinical Trial Officials and Contacts

Kevin D. Cooper, MD Principal Investigator Louis Stokes DVA Medical Center, Cleveland, Ohio 44106  

Overall Contact: Jona Lee Matevish, MPH 216-844-7834 jlm57@case.edu

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00470392

Study ID Number: IMMB-004-06S

ClinicalTrials.gov Identifier: NCT00470392

Health Authority: United States: Federal Government

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