Study Comparing Tetrathiomolybdate vs Standard Treatment in Primary Biliary Cirrhosis

NCT00805805 | Completed Phase 3 DMC

• 1 other identifier: PBC
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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

Conditions

Primary Biliary Cirrhosis

Keywords

Copper; ceruloplasmin; tetrathiomolybdate

Outcome Measures

Primary Outcomes (1)

• Improvement in drug treated group vs placebo group in two liver function tests and one serum cytokine measurement

  2 years

Secondary Outcomes (1)

• Improvement in drug treated group vs placebo group in serum CRP or interleukin-1-beta-levels

  2 years

Study Arms (2)

1

EXPERIMENTAL

Tetrathiomolybdate with ursodiol

Drug: Tetrathiomolybdate

2

PLACEBO COMPARATOR

Placebo with ursodiol

Other: Placebo

Interventions

Tetrathiomolybdate DRUG

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).

1

Placebo OTHER

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

2

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• George Brewer: lead
• FDA Office of Orphan Products Development: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

tetrathiomolybdate

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 8, 2008
• First Posted: December 10, 2008
• Study Start: April 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: May 23, 2017

Record last verified: 2017-05

Locations

US (1)