Optimization of UV Radiation Therapy in Psoriasis
Information source: Department of Veterans Affairs
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Psoriasis
Intervention: Imiquimod (Drug); Clobetasol (glucosteroid) (Drug); Excimer laser (UVB light) treatment (Device)
Phase: Phase 4
Status: Recruiting
Sponsored by: Department of Veterans Affairs Official(s) and/or principal investigator(s):
Kevin D Cooper, MD, Principal Investigator, Affiliation: VA Medical Center, Cleveland
Overall contact:
Benjamin R Bohaty, BS, Phone: (513) 255-5436, Email: brb64@case.edu
Summary
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
Clinical Details
Official title: Mechanistically-Based Optimization of UV Radiation Therapy in Psoriasis
Study design: Treatment, Non-Randomized, Open Label, Active Control, Crossover Assignment, Efficacy Study
Primary outcome: T cell apoptosis
Secondary outcome: Lesional Psoriasis Area and Assessment
Detailed description:
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.)
Eligibility
Minimum age: 21 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
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 cm 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
Locations and Contacts
Benjamin R Bohaty, BS, Phone: (513) 255-5436, Email: brb64@case.edu
VA Medical Center, Cleveland, Cleveland, Ohio 44106, United States; Recruiting
Benjamin R Bohaty, BS, Phone: 513-255-5436, Email: brb64@case.edu
Kevin D Cooper, MD, Principal Investigator
Additional Information
The National Institute of Arthritis, Musculoskeletal, and Skin Diseases website providing fast facts on health topics, including psoriasis This is the home page for the Murdough Family Center for Psoriasis.
Starting date: May 2007
Ending date: May 2010
Last updated: February 9, 2009
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