A Study of Tetrathiomolybdate in the Treatment of Psoriasis Vulgaris
A Study of Tetrathiomolybdate in the Treatment of Psoriasis Vulgaris
Psoriasis is a common skin disease affecting an estimated 2.6% of the US population. It is a
 chronic, recurrent condition for which there is no cure, but there are ways to control it.
 Psoriasis is characterized by epidermal hyperplasia (abnormal increase in the number of
 normal cells of the outer layer of the skin). Tetrathiomolybdate (TM), a copper chelator (a
 drug that removes copper from the bloodstream) was first created to treat Wilson's disease, a
 disorder caused by too much copper in the blood. Studies in animals have since shown that TM
 may also prevent the formation of new blood vessels and may also block the key components of
 inflammation (swelling, redness, and pain) caused by psoriasis. TM is not approved by the FDA
 for any use yet. It is an investigational drug used for clinical research. We propose to test
 whether a new treatment with TM can in fact improve or stabilize psoriasis.
The purpose of this study is to evaluate the safety and efficacy of Tetrathiomolybdate in
 psoriasis therapy. Psoriasis is a common skin disease affecting an estimated 2.6% of the US
 population. It is a chronic, recurrent condition for which there is no cure but ways to
 control it. Psoriasis is characterized by epidermal hyperplasia, increased dermal
 angiogenesis, and infiltration of activated lymphocytes. Beginning with the observation that
 cyclosporin A, whose primary action is to inhibit lymphokine release and proliferation of T
 cells, was effective in the treatment of psoriasis, the last two decades saw a major paradigm
 shift in the pathogenesis of psoriasis, from a view of psoriasis as a disease of epidermal
 origin to a view of it as an epidermal response to immunological injury. In fully activated T
 cells in psoriatic skin, the T1/T2 cytokine balance is shifted in favor of T1 expression,
 with production of IL-2 and IFN-γ. Activated T1 lymphocytes also produce TNF-α. This is a
 pivotal cytokine that regulates an array of proinflammatory mediators. Recently, anti-TNF-α
 therapy using a chimeric anti-TNF-α monoclonal antibody (infliximab) and a
 TNF-receptor-immunoglobulin fusion protein (etanercept) have shown to be highly effective in
 patients with severe psoriasis. Efforts to treat psoriasis by inhibiting neovascularization
 of psoriatic plaques have also been shown to be effective. A randomized phase I/II clinical
 trial using Neovastat, a naturally occurring inhibitor of angiogenesis, resulted in
 dose-dependent improvement in the Psoriasis Area and Severity Index (PASI) score, thus
 providing further evidence that altered angiogenesis is an integral part of psoriasis
 pathophysiology. Since TM has proven antiangiogenic and anti-TNF-α activities, we are very
 encouraged that TM therapy will be beneficial in psoriasis.
Inclusion Criteria:

 -  18 + years of age

 -  Psoriasis vulgaris involving greater than 5% total body surface area

 -  No disease states or physical conditions which would impair evaluation of the test
 sites

 -  Willing and able to take test medications as directed in the protocol, make evaluation
 visits and follow protocol restrictions

 -  Failed systemic therapy for psoriasis (e.g., PUVA, retinoids, systemic steroids,
 methotrexate, etc.)

 -  Signed, written, witnessed informed consent form

 -  You must live within a reasonable driving distance of Ann Arbor, Michigan, and/or be
 able to attend all of the scheduled appointments during the study.

 Exclusion Criteria:

 -  Use of any topical psoriasis treatment within weeks prior to the start of the study

 -  Use of any systemic medication within 4 weeks prior to the start of the study

 -  Involvement in an investigational study within the previous 4 weeks

 -  Inability to give informed consent

 -  History of drug dependency or alcoholism

 -  Severe infection within 4 weeks prior to study entry or the presence of chronic
 infection

 -  Significant psychiatric disorder

 -  Screening laboratory values which exceed the following limits:

 -  Hematology - WBC <3,500 cells/mm3, Hb <10.5g/dl, platelets <100,000 cells/mm3;

 -  Renal function test - creatinine >1.5 mg/dl;

 -  Liver function tests - AST, alkaline phosphatase or total bilirubin more than
 twice the upper limits of normal, and a prothrombin time above the normal range.

 -  Pregnancy or breast feeding a baby. Sexually active women of reproductive age must use
 an acceptable form of birth control.