title: Open-label phase 1b pilot study to assess the antiviral efficacy of simvastatin combined with sertraline in chronic hepatitis C patients.
abstract: BACKGROUND
  3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors inhibit HCV replication in vitro. The combination of sertraline and simvastatin has synergistic antiviral activity in vitro, but there are no prior in vivo studies. Our aims were to prospectively assess the antiviral efficacy and safety of this drug combination in chronic hepatitis C (CHC) patients.
  
  
  METHODS
  A total of 15 CHC adults (including 1 control subject) that were treatment-naive or prior partial responders/relapsers to standard-of-care therapy were enrolled at four centres (2 in Singapore and 2 in the US). Patients received simvastatin 40 mg once daily and sertraline 50 mg once daily for 7 days, and then 80 mg once daily and 100 mg once daily, respectively, for another 21 days with a 14-day follow-up.
  
  
  RESULTS
  Of the 15 CHC patients, 13 completed the study. Subjects were mostly Caucasian (8/15), mean age 49.1 ±9 years and the genotype distribution was 1=10, 2=2 and 3=3. No subject discontinued dosing due to adverse events. Mean HCV RNA change from baseline was from -0.005 to -0.236 log(10) IU/ml across study intervals. Three subjects had transient >1 log(10) HCV RNA declines. No subject achieved >2 log(10) HCV RNA decline.
  
  
  CONCLUSIONS
  The combination of sertraline and simvastatin is well-tolerated over the short-term, but has no significant antiviral or anti-inflammatory response in CHC patients. This may reflect in vivo differences in synergy between statin and/or selective serotonin reuptake inhibitors and incomplete inhibition of membrane protein prenylation with statin therapy.
authors.affiliation: Duke Clinical Research Unit and DUMC, Durham, NC, USA. keyur.patel@duke.edu
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Seng G
authors.initials: SG
authors.lastname: Lim
authors.forename: Chow W
authors.initials: CW
authors.lastname: Cheng
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.forename: Hans L
authors.initials: HL
authors.lastname: Tillmann
authors.forename: Narinder
authors.initials: N
authors.lastname: Chopra
authors.forename: Ralf
authors.initials: R
authors.lastname: Altmeyer
authors.forename: John C R
authors.initials: JC
authors.lastname: Randle
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D020280:Sertraline / Q000008:administration & dosage* / Q000627:therapeutic use; D019821:Simvastatin / Q000008:administration & dosage* / Q000627:therapeutic use; D012846:Singapore; D014481:United States
chemical_list: D000998:Antiviral Agents; D000960:Hypolipidemic Agents; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D019821:Simvastatin; C100416:peginterferon alfa-2a