Study Comparing Tetrathiomolybdate vs Standard Treatment in Primary Biliary Cirrhosis

• ClinicalTrials.gov Identifier: NCT00805805
• Recruitment Status: Completed
• First Posted: December 10, 2008
• Last Update Posted: May 23, 2017
• Sponsor: George Brewer
• Collaborator: FDA Office of Orphan Products Development
• Information provided by (Responsible Party): George Brewer, University of Michigan

Study Description

Brief Summary:

The University of Michigan is conducting a study investigating a potential new treatment aimed at slowing/halting progression of primary biliary cirrhosis. This will be a 2 arm double blind study in which half of the patients will be randomly selected to receive a placebo (capsule with no active ingredient) and half will receive the new treatment drug, tetrathiomolybdate. Neither the patient nor the treating physician will know which arm the patient is in. The length of the study for each patient is 24 months of drug therapy. Lab draws will be necessary weekly for the first 6 weeks of the study, followed by every other week for 3 weeks, and then monthly for the remainder of the 2 year period. In addition, intermittent history and physicals and urine samples will also be necessary. There is no cost to you for any experimental treatment. All patients in both arms will continue on ursodiol and receive standard of care treatment

Condition or disease	Intervention/treatment	Phase
Primary Biliary Cirrhosis	Drug: Tetrathiomolybdate; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase III Trial of Tetrathiomolybdate (TM) in Primary Biliary Cirrhosis
• Study Start Date: April 2006
• Actual Primary Completion Date: December 2008
• Actual Study Completion Date: December 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Tetrathiomolybdate with ursodiol	Drug: Tetrathiomolybdate; 120 mg/day, divided as 20 mg three times/day with meals and 60 mg away from food at bedtime, for one week to test gastric tolerance. Increased to 180 mg/day, divided as 40 mg three times/day with meals and 60 mg away from food at bedtime. Serum ceruloplasmin levels measured weekly will be used as a surrogate measure of copper status, with a target of 10-15 mg/dl (normal 20-40). When target Cp levels are reached, usually in 4-8 weeks, a maintenance dose of usually 40-80 mg of TM/day, divided half with a major meal, and half away from food at bedtime will be established (vary from 10 mg to 120 mg/day).
Placebo Comparator: 2; Placebo with ursodiol	Other: Placebo; Arm 2 will basically mirror Arm 1 with the patients receiving 120 mg/day, divided as 20 mg three times/day with meals and 60 mg away from food at bedtime the first week. Increased to 180 mg/day, divided as 40 mg three times/day with meals and 60 mg away from food at bedtime. With the dosage being reduced at about the same frequency as the patients receiving TM

Outcome Measures

Primary Outcome Measures :

1. Improvement in drug treated group vs placebo group in two liver function tests and one serum cytokine measurement [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. Improvement in drug treated group vs placebo group in serum CRP or interleukin-1-beta-levels [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Generally medically healthy
• Age 18 and older
• Documented primary biliary cirrhosis
• Alkaline phosphatase > 137

Exclusion Criteria:

• Severe liver decompensation
• Requirement for renal dialysis
• Pregnancy or nursing
• Meld score > 15 (13-15 will require a physician's clinical judgment)
• Uncontrolled congestive heart failure
• Severe diabetic neuropathy
• Severe pulmonary disease
• Advanced cancer
• Requirement for steroid therapy
• Uncontrolled ascites, variceal hemorrhage or spontaneous bacterial peritonitis
• Pregnant or nursing

Contacts and Locations

Locations

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

George Brewer

FDA Office of Orphan Products Development

More Information

• Responsible Party: George Brewer, Professor, University of Michigan
• ClinicalTrials.gov Identifier: NCT00805805
• Other Study ID Numbers: PBC
• First Posted: December 10, 2008
• Last Update Posted: May 23, 2017
• Last Verified: May 2017

Keywords provided by George Brewer, University of Michigan:

Copper; ceruloplasmin; tetrathiomolybdate

Additional relevant MeSH terms:

Liver Cirrhosis; Liver Cirrhosis, Biliary; Fibrosis; Pathologic Processes; Liver Diseases; Digestive System Diseases; Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Tetrathiomolybdate; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents