Study Comparing Tetrathiomolybdate vs Standard Treatment in Primary Biliary Cirrhosis

Phase III Trial of Tetrathiomolybdate (TM) in Primary Biliary Cirrhosis

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

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Drug: Tetrathiomolybdate; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Improvement in drug treated group vs placebo group in two liver function tests and one serum cytokine measurement	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Improvement in drug treated group vs placebo group in serum CRP or interleukin-1-beta-levels	2 years

Collaborators and Investigators

• Sponsor: George Brewer
• Collaborators: FDA Office of Orphan Products Development

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: December 8, 2008
• First Submitted That Met QC Criteria: December 8, 2008
• First Posted (Estimate): December 10, 2008

Study Record Updates

• Last Update Posted (Actual): May 23, 2017
• Last Update Submitted That Met QC Criteria: May 19, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Copper; ceruloplasmin; tetrathiomolybdate
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Chelating Agents; Sequestering Agents; Tetrathiomolybdate
• Other Study ID Numbers: PBC