title: A Randomized, Placebo-Controlled Clinical Trial of Efficacy and Safety: Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis.
abstract: OBJECTIVE
  Fatigue is a common symptom of primary biliary cirrhosis (PBC), and is associated with an impaired quality of life.
  
  
  OBJECTIVE
  No studies have assessed the use of modafinil in fatigue related to PBC in a controlled manner.
  A randomized, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of modafinil for the treatment of fatigue in PBC. Forty patients were randomized to modafinil (n = 20) or placebo (n = 20) for 12 weeks. A verbal report of fatigue for at least 6 months was required for enrollment. Modafinil was administered at 100 mg by mouth once daily; a change by 50 mg every 2 weeks (maximum: 200 mg once daily) was allowed, depending on the subject's response to treatment. The primary outcome was defined as a ≥50% improvement in fatigue severity [quantified by the Fisk Fatigue Impact Scale (FFIS)] after 12 weeks of treatment, compared with baseline values.
  
  
  RESULTS
  Thirty-three PBC patients completed the study. After 12 weeks of therapy, only 5 patients had a ≥50% reduction in FFIS scores: 3 patients (17.6%) in the modafinil arm and 2 (12.5%) in the placebo arm (P = 1.00). Change in median FFIS score was not statistically different between patients in the 2 treatment groups (P = 0.36). Modafinil was associated with minimal adverse events (headaches, diarrhea, and rash).
  
  
  CONCLUSIONS
  In patients with PBC who have fatigue, treatment with modafinil for 12 weeks was safe and fairly well tolerated; however, it did not result in beneficial effects on fatigue compared with patients treated with placebo (CONSORT Table 1). ClinicalTrials.gov identifier NCT00943176.
authors.affiliation: 1Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN; 2Division of Gastroenterology and Hepatology, Case Western Reserve University, Louis Stokes Cleveland VA Medical Center and Case Medical Center, Cleveland, OH; 3Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ; and 4College of Health Solutions, Arizona State University, Phoenix, AZ.
authors.forename: Marina G
authors.initials: MG
authors.lastname: Silveira
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Gossard
authors.forename: Alisha C
authors.initials: AC
authors.lastname: Stahler
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Jorgensen
authors.forename: Janice L
authors.initials: JL
authors.lastname: Petz
authors.forename: Ahmad H
authors.initials: AH
authors.lastname: Ali
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lindor
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D004311:Double-Blind Method; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000150:complications*; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D016896:Treatment Outcome; D064690:Wakefulness-Promoting Agents / Q000627:therapeutic use*
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil