Mechanistically-based Optimization of UV Radiation Therapy in Psoriasis

This study has been terminated.
(Recruiting complete and administrative termination)
Sponsor:
Collaborator:
University Hospital Case Medical Center
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00470392
First received: May 4, 2007
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention
Psoriasis
Drug: Imiquimod
Drug: Clobetasol

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Single Blind (Subject)
Official Title: Mechanistically-based Optimization of UV Radiation Therapy in Psoriasis

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Number of Subjects With Elevated MyxA [ Time Frame: Biopsy samples for analysis were taken 1 hour post UVB treatment ] [ Designated as safety issue: No ]
    Lesions were treated with either Imiquimod or Clobetasol cream. Lesions were subsequently treated with UVB and biopsied. From the biopsy samples obtained from the Imiquimod arm, quantitative PCR was performed to measure levels of Myx A, an imiquimod response gene.


Secondary Outcome Measures:
  • Number of Subjects With Improvement in Lesional Psoriasis Area and Assessment (PASI) Score After Imiquimod and UVB Treatment [ Time Frame: 2 weeks after Imiquimod and UVB ] [ Designated as safety issue: No ]
    The PASI is a disease burden measure that integrates area, erythema, thickness and scale of each target lesion. The severity score for each region is calculated by adding the scores for redness, thickness and scale (each of which are graded from 0 to 4). The maximum severity score is 12. The higher the PASI, the worse the disease. Thus, an improvement in PASI score is a lower score than the pre-treatment PASI.

  • Number of Subjects With a 1.5 Fold Increase in mRNA Expression of GRAMD1A and DMXL2 [ Time Frame: Biopsy samples for analysis were taken 1 hour post UVB treatment ] [ Designated as safety issue: No ]
    Based upon upregulated mRNA expression of MyxA in 1 out of 7 patients treated with Imiquimod, a list of alternative target genes responsive to Imiquimod was generated. The target mRNAs examined included GRAMD1A, IL2RA, TGHD1, DMXL2. The target gene was consider upregulated if there was a 1.5 fold increase in the mRNA expression of the target gene.


Enrollment: 9
Study Start Date: May 2007
Study Completion Date: July 2012
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Imiquimod
Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.
Drug: Imiquimod
Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Imiquimod (5% topical cream) was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.
Other Name: Aldara
Clobetasol
Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.
Drug: Clobetasol
Each study subject served as his/her own control. For this arm of the study, topical vehicle was applied to one plaque for 5 days. Clobetasol propionate 0.05% was applied to two psoriasis plaques for 5 days. Skin biopsies were taken from half of each of the 3 plaques at specific time points after completion of topical pre-treatment. The other half of the plaques were exposed to UVB light (via Excimer laser). Biopsies were subsequently taken at a specified time point.
Other Name: Temovate

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 demonstrated 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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The presence of plaque-type psoriasis in areas of the trunk, buttocks, or extremities that are amenable to biopsy and evaluable disease in at least 2 cm target treatment sites separated by 1 cm
  • Age 18-80, 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 1 week 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 local anesthetic
  • Inability to provide informed consent
  • Pregnancy and /or lactating
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00470392

Locations
United States, Ohio
VA Medical Center, Cleveland
Cleveland, Ohio, United States, 44106
University Hospital Case Medical Center
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
University Hospital Case Medical Center
Investigators
Principal Investigator: Kevin D Cooper, MD VA Medical Center, Cleveland
  More Information

Additional Information:
No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00470392     History of Changes
Other Study ID Numbers: IMMB-004-06S
Study First Received: May 4, 2007
Results First Received: September 26, 2013
Last Updated: February 12, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
Erythema
optimization
Papule
Plaque
pretreatment
T cells
UVB laser light
psoriasis
topical administration

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Clobetasol
Imiquimod
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Adjuvants, Immunologic
Immunologic Factors
Antineoplastic Agents
Interferon Inducers

ClinicalTrials.gov processed this record on October 19, 2014