Single Daily Dosage of Trientine for Maintenance Treatment for Wilson Disease

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).

Timeline

Start

2010-01

Primary completion

2011-07

Completion

2011-07

Publications

• Background Roberts EA, Schilsky ML; Division of Gastroenterology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada. A practice guideline on Wilson disease. Hepatology. 2003 Jun;37(6):1475-92. doi: 10.1053/jhep.2003.50252. No abstract available.
• Background Schilsky ML, Scheinberg IH, Sternlieb I. Liver transplantation for Wilson's disease: indications and outcome. Hepatology. 1994 Mar;19(3):583-7. doi: 10.1002/hep.1840190307.
• Background Emre S, Atillasoy EO, Ozdemir S, Schilsky M, Rathna Varma CV, Thung SN, Sternlieb I, Guy SR, Sheiner PA, Schwartz ME, Miller CM. Orthotopic liver transplantation for Wilson's disease: a single-center experience. Transplantation. 2001 Oct 15;72(7):1232-6. doi: 10.1097/00007890-200110150-00008.
• Background Askari FK, Greenson J, Dick RD, Johnson VD, Brewer GJ. Treatment of Wilson's disease with zinc. XVIII. Initial treatment of the hepatic decompensation presentation with trientine and zinc. J Lab Clin Med. 2003 Dec;142(6):385-90. doi: 10.1016/S0022-2143(03)00157-4.
• Background Brewer GJ, Dick RD, Johnson VD, Fink JK, Kluin KJ, Daniels S. Treatment of Wilson's disease with zinc XVI: treatment during the pediatric years. J Lab Clin Med. 2001 Mar;137(3):191-8. doi: 10.1067/mlc.2001.113037.
• Background Ferenci P. Wilson's Disease. Clin Gastroenterol Hepatol. 2005 Aug;3(8):726-33. doi: 10.1016/s1542-3565(05)00484-2.
• Background Brewer GJ, Askari F, Lorincz MT, Carlson M, Schilsky M, Kluin KJ, Hedera P, Moretti P, Fink JK, Tankanow R, Dick RB, Sitterly J. Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease. Arch Neurol. 2006 Apr;63(4):521-7. doi: 10.1001/archneur.63.4.521.
• Background Scheinberg IH, Jaffe ME, Sternlieb I. The use of trientine in preventing the effects of interrupting penicillamine therapy in Wilson's disease. N Engl J Med. 1987 Jul 23;317(4):209-13. doi: 10.1056/NEJM198707233170405.
• Background Walshe JM. Treatment of Wilson's disease with trientine (triethylene tetramine) dihydrochloride. Lancet. 1982 Mar 20;1(8273):643-7. doi: 10.1016/s0140-6736(82)92201-2.
• Background Ferenci P, Caca K, Loudianos G, Mieli-Vergani G, Tanner S, Sternlieb I, Schilsky M, Cox D, Berr F. Diagnosis and phenotypic classification of Wilson disease. Liver Int. 2003 Jun;23(3):139-42. doi: 10.1034/j.1600-0676.2003.00824.x.
• Ala A, Aliu E, Schilsky ML. Prospective pilot study of a single daily dosage of trientine for the treatment of Wilson disease. Dig Dis Sci. 2015 May;60(5):1433-9. doi: 10.1007/s10620-014-3495-6. Epub 2015 Jan 21.

Drugs

Indications