Study Comparing Tetrathiomolybdate vs Standard Treatment in Primary Biliary Cirrhosis - Full Text View

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:

Genetics Home Reference related topics: North American Indian childhood cirrhosis progressive familial intrahepatic cholestasis

MedlinePlus related topics: Cirrhosis

Genetic and Rare Diseases Information Center resources: Primary Biliary Cholangitis

U.S. FDA Resources

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

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 (Adult, Senior)
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

FDA Office of Orphan Products Development

More Information


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:


Fibrosis Liver Cirrhosis Liver Cirrhosis, Biliary Pathologic Processes Liver Diseases Digestive System Diseases Cholestasis, Intrahepatic Cholestasis Bile Duct Diseases Biliary Tract Diseases Tetrathiomolybdate Molybdenum	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 Trace Elements Micronutrients

ClinicalTrials.gov processed this record on September 28, 2016