Clinical Trial: Single Daily Dosage of Trientine for Maintenance Treatment for Wilson Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Single Daily Dosage of Trientine for Maintenance Treatment for Wilson Disease

Brief Summary:

Hypothesis: The investigators postulate that patients with Wilson disease who are asymptomatic or who have been effectively treated for their symptoms and are in a maintenance phase therapy can be safely and effectively treated with a single daily dosage of the chelating agent trientine.

Specific Aims: To demonstrate that a single daily treatment with trientine is as effective or better than a patient's current maintenance therapy. This will be accomplished by performance of a case control prospective study of patients on their prior therapy, and during a period of treatment with a single weight based dose regimen of trientine.

The primary endpoint for this study is the demonstration of equivalence to a patient's prior therapy. Secondary endpoints include: 1) demonstration of stability or improvement in parameters of copper metabolism; 2) improvement in adherence to therapy; 3) no progression of liver disease (defined by changes in synthetic function, albumin and INR, and fibrosis by Fibrotest).


Detailed Summary:

Wilson disease is a genetic disorder of copper metabolism inherited in an autosomal recessive fashion that afflicts ~1/30,000 individuals. Treatment for these individuals consists of medical therapy, which is life-long, or liver transplantation. Medical therapy utilizes chelating agents, penicillamine and trientine, or zinc, each given in multiple daily dosages (1). It is estimated that ~10-50% of individuals have some period of non-adherence to their therapy during their life-time. The consequences of non-adherence include liver injury, liver failure, neurological impairment and death. Some non-adherent individuals can be rescued by reinstitution of medical therapy, while others require liver transplantation (1-4). In addition to the human suffering engendered by the advance in an individuals disease suffered from non-adherence, the physical or mental disability suffered or the need for liver transplantation adds greatly to their cost of life-time care. Simplifying the current treatment regimen for long-term maintenance therapy for Wilson disease should improve patient adherence. This will translate into a positive long-term benefit for patients, their caregivers and supports, and for society as a whole.

Current maintenance therapy for Wilson disease includes the chelating agents penicillamine and trientine, or zinc. Multiple daily dosages (three or four) are recommended from early studies on these medications, by the manufacturer and by treating physicians (1,5-8). As noted above, patient adherence to treatment, and in particular to multiple daily dosages is often incomplete. There has been an increase in the treatment of other common disorders with medication that can be administered as a single daily dosage. As an example, some anti-hypertensives and antidepressants are available in extended release formulations, making a single daily dosage possible. None of the curr
Sponsor: Yale University

Current Primary Outcome:

  • ALT [ Time Frame: Pre Treatment (mean) ]
    Alanine transaminase
  • ALT [ Time Frame: Months 1,2,3,6,9,12 (mean) ]
    Alanine transaminase
  • Cu Serum [ Time Frame: Pre Treatment (mean) ]
  • Cu Serum [ Time Frame: Months 1,2,3,6,9,12 (mean) ]


Original Primary Outcome:

  • ALT [ Time Frame: -3,-2,-1, baseline, 1, 2, 3, 6, 9, 12 months ]
    Alanine transaminase
  • Ceruloplasmin [ Time Frame: -3,-2,-1, baseline, 1, 2, 3, 6, 9, 12 months ]
    Ceruloplasmin is the major copper-carrying protein in the blood.


Current Secondary Outcome:

  • INR [ Time Frame: Pre Treatment (mean) ]
    The International Normalized Ratio (INR) is a standard way to describe the time it takes for blood to clot; an INR range of 0.8 to 1.2 is considered normal for a healthy person who is not using oral anticoagulant therapy
  • INR [ Time Frame: Months 1,2,3,6,9,12 (mean) ]
    The International Normalized Ratio (INR) is a standard way to describe the time it takes for blood to clot; an INR range of 0.8 to 1.2 is considered normal for a healthy person who is not using oral anticoagulant therapy
  • Albumin [ Time Frame: Pre Treatment (mean) ]
  • Albumin [ Time Frame: Months 1,2,3,6,9,12 (mean) ]
  • Cu Urine [ Time Frame: Pre Treatment (mean) ]
  • Cu Urine [ Time Frame: Months 1,2,3,6,9,12 (mean) ]
  • Zn Urine [ Time Frame: Pre Treatment (mean) ]
  • Zn Urine [ Time Frame: Months 1,2,3,6,9,12 (mean) ]


Original Secondary Outcome:

  • Clinical status [ Time Frame: 1 year ]
    The primary objective of the statistical analysis will be to compare parameters pertaining to adverse events (AEs) and clinical status for subjects receiving "current standard therapy" vs. Trientine therapy.
  • Other LFTs [ Time Frame: -3,-2,-1, baseline, 1, 2, 3, 6, 9, 12 months ]
    Liver function tests


Information By: Yale University

Dates:
Date Received: November 11, 2011
Date Started: January 2010
Date Completion:
Last Updated: May 19, 2014
Last Verified: May 2014