Study Comparing Tetrathiomolybdate vs Standard Treatment in Primary Biliary Cirrhosis

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of Michigan
ClinicalTrials.gov Identifier:
NCT00805805
First received: December 8, 2008
Last updated: January 25, 2013
Last verified: December 2008
  Purpose

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 Intervention Phase
Primary Biliary Cirrhosis
Drug: Tetrathiomolybdate
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase III Trial of Tetrathiomolybdate (TM) in Primary Biliary Cirrhosis

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Improvement in drug treated group vs placebo group in two liver function tests and one serum cytokine measurement [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improvement in drug treated group vs placebo group in serum CRP or interleukin-1-beta-levels [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: April 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00805805

Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
  More Information

No publications provided

Responsible Party: Fred Askari MD, PhD, Principal investigator, Univeristy of Michigan
ClinicalTrials.gov Identifier: NCT00805805     History of Changes
Other Study ID Numbers: PBC
Study First Received: December 8, 2008
Last Updated: January 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan:
Copper
ceruloplasmin
tetrathiomolybdate

Additional relevant MeSH terms:
Liver Cirrhosis, Biliary
Liver Cirrhosis
Fibrosis
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases
Pathologic Processes
Tetrathiomolybdate
Molybdenum
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Chelating Agents
Trace Elements
Micronutrients

ClinicalTrials.gov processed this record on April 15, 2014