Single Daily Dosage of Trientine for Maintenance Treatment for Wilson Disease

NCT01472874 | Completed Results

• 2 other identifiers: 0902004694ORPH-SYP-001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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).

Conditions

Wilson Disease

Keywords

Wilson Disease; Trientine; One Daily Dosage

Outcome Measures

Primary Outcomes (4)

• ALT

  Alanine transaminase

  Pre Treatment (mean)

• ALT

  Alanine transaminase

  Months 1,2,3,6,9,12 (mean)

• Cu Serum

  Pre Treatment (mean)

• Cu Serum

  Months 1,2,3,6,9,12 (mean)

Secondary Outcomes (8)

• INR

  Pre Treatment (mean)

• INR

  Months 1,2,3,6,9,12 (mean)

• Albumin

  Pre Treatment (mean)

• Albumin

  Months 1,2,3,6,9,12 (mean)

• Cu Urine

  Pre Treatment (mean)

Study Arms (1)

Once a day Trientine

EXPERIMENTAL

Patients receive once a day trientine

Drug: Once a day Trientine

Interventions

Once a day Trientine DRUG

Trientine at a dosage of \~15 mg/kg rounded upwards to the nearest 250 or 300 mg in a single daily dosage. The entire daily dosage will be taken at once in the AM an hour before any meal. Duration of the study is 1 year.

Also known as: Syprine

Once a day Trientine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Established diagnosis of Wilson Disease:
• That have been treated for at least 1 year
• Compensated liver disease and/or stable neurological or psychiatric disease.
• Normal or minimal elevation of serum ALT (\<2 times upper limit of normal)
• Non-ceruloplasmin copper \<25 mcg/dl

You may not qualify if:

• Wilson disease diagnosis not well established Wilson disease treated for less than one year Decompensated liver disease (ascites, jaundice, encephalopathy, bleeding due to portal hypertension) Liver disease with elevations of ALT \> 2 times upper limit of normal A female who is pregnant or intends to become pregnant

Sponsors & Collaborators

• Yale University: lead
• Bausch Health Americas, Inc.: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, United States

Location

Related Publications (11)

• 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.

  PMID: 12774027 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.

  PMID: 8119682 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.

  PMID: 11602847 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.

  PMID: 14713890 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.

  PMID: 11241029 BACKGROUND

• Ferenci P. Wilson's Disease. Clin Gastroenterol Hepatol. 2005 Aug;3(8):726-33. doi: 10.1016/s1542-3565(05)00484-2.

  PMID: 16233999 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.

  PMID: 16606763 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.

  PMID: 3600712 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.

  PMID: 6121964 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.

  PMID: 12955875 BACKGROUND

• 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.

  PMID: 25605552 DERIVED

MeSH Terms

Conditions

Hepatolenticular Degeneration

Interventions

Trientine

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr. Schilsky
• Organization: Yale

michael.schilsky@yale.edu

203-785-2565

Study Officials

• Michael Schilsky, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2011
• First Posted: November 17, 2011
• Study Start: January 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: April 15, 2020
• Results First Posted: May 19, 2014

Record last verified: 2020-04

Locations

US (1)