A Study of Tetrathiomolybdate in the Treatment of Psoriasis Vulgaris

This study has been completed.
Sponsor:
Information provided by:
University of Michigan
ClinicalTrials.gov Identifier:
NCT00113542
First received: June 8, 2005
Last updated: August 6, 2008
Last verified: August 2008
  Purpose

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.


Condition Intervention Phase
Psoriasis
Drug: Tetrathiomolybdate (TM)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Study of Tetrathiomolybdate in the Treatment of Psoriasis Vulgaris

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Improvement in psoriasis as measured by PASI (psoriasis area and severity index)
  • Erythema, scaling, and thickness of target lesions

Secondary Outcome Measures:
  • Cytokine and laboratory values will be compared to baseline to test the hypothesis that TM will affect the level of TNF alpha, IL-1, C-protein, and TGF.

Estimated Enrollment: 10
Study Start Date: June 2004
Estimated Study Completion Date: June 2005
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00113542

Locations
United States, Michigan
University of Michigan Department of Dermatology
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Investigators
Study Chair: John J Voorhees, MD University of Michigan
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00113542     History of Changes
Other Study ID Numbers: Derm 508
Study First Received: June 8, 2005
Last Updated: August 6, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan:
Psoriasis
Tetrathiomolybdate

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Tetrathiomolybdate
Molybdenum
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Chelating Agents
Trace Elements
Micronutrients

ClinicalTrials.gov processed this record on July 20, 2014