TY - JOUR
T1 - Treatment of primary biliary cirrhosis with tetrathiomolybdate
T2 - results of a double-blind trial
AU - Askari, Fred
AU - Innis, Dawna
AU - Dick, Robert B.
AU - Hou, Guoqing
AU - Marrero, Jorge
AU - Greenson, Joel
AU - Brewer, George J.
N1 - Funding Information:
Supported by Grant FD-02590-02 from the U.S. Food and Drug Administration's Orphan Products Office, the General Clinical Research Center of the University of Michigan Hospitals , Grant MO1-RR000042 from the National Institutes of Health , and Grant Ul1-RR024986 Clinical and Translational Science Awards .
PY - 2010/3
Y1 - 2010/3
N2 - The results of a double-blind trial of tetrathiomolybdate therapy and standard of care, versus placebo and standard of care treatment, in primary biliary cirrhosis patients are presented. Baseline studies of liver function, various safety variables, ceruloplasmin, a liver biopsy for histologic analysis, and for various cytokine analyses were carried out. Patients were observed every 4 months for up to 2 years of treatment by a hepatologist for clinical evaluation and repeat of all the baseline studies except liver biopsy, which was repeated at 2 years. The primary end points were improvement in 2 liver function tests and in 1 inflammatory cytokine. Fifteen placebo patients were followed for an average of 13 months, and 13 tetrathiomolybdate patients were followed for an average of 14 months. The predefined primary end points for efficacy were met. Tetrathiomolybdate was well tolerated. Because tetrathiomolybdate has been shown in numerous animal studies to inhibit autoimmune and inflammatory processes, and because primary biliary cirrhosis is an autoimmune attack on bile ducts, these positive findings on efficacy of tetrathiomolybdate therapy in primary biliary cirrhosis fit with the animal studies and suggest the need for a longer clinical trial to examine transplant-free survival.
AB - The results of a double-blind trial of tetrathiomolybdate therapy and standard of care, versus placebo and standard of care treatment, in primary biliary cirrhosis patients are presented. Baseline studies of liver function, various safety variables, ceruloplasmin, a liver biopsy for histologic analysis, and for various cytokine analyses were carried out. Patients were observed every 4 months for up to 2 years of treatment by a hepatologist for clinical evaluation and repeat of all the baseline studies except liver biopsy, which was repeated at 2 years. The primary end points were improvement in 2 liver function tests and in 1 inflammatory cytokine. Fifteen placebo patients were followed for an average of 13 months, and 13 tetrathiomolybdate patients were followed for an average of 14 months. The predefined primary end points for efficacy were met. Tetrathiomolybdate was well tolerated. Because tetrathiomolybdate has been shown in numerous animal studies to inhibit autoimmune and inflammatory processes, and because primary biliary cirrhosis is an autoimmune attack on bile ducts, these positive findings on efficacy of tetrathiomolybdate therapy in primary biliary cirrhosis fit with the animal studies and suggest the need for a longer clinical trial to examine transplant-free survival.
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U2 - 10.1016/j.trsl.2009.09.009
DO - 10.1016/j.trsl.2009.09.009
M3 - Article
C2 - 20171597
AN - SCOPUS:76549123971
SN - 1931-5244
VL - 155
SP - 123
EP - 130
JO - Translational Research
JF - Translational Research
IS - 3
ER -