title: A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome.
abstract: OBJECTIVE
  Minocycline rescued synaptic abnormalities and improved behavior in the fragile X mouse model. Previous open-label human studies demonstrated benefits in individuals with fragile X syndrome (FXS); however, its efficacy in patients with FXS has not been assessed in a controlled trial.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, crossover trial in individuals with FXS, aged 3.5 years to 16 years (n = 55, mean age 9.2 [SD, 3.6] years). Participants were randomized to minocycline or placebo for 3 months and then switched to the other treatment.
  
  
  RESULTS
  Sixty-nine subjects were screened and 66 were randomized. Fifty-five subjects (83.3%) completed at least the first period and 48 (72.7%) completed the full trial. Intention-to-treat analysis demonstrated significantly greater improvements in one primary outcome, Clinical Global Impression Scale-Improvement after minocycline compared with placebo (2.49 ± 0.13 and 2.97 ± 0.13, respectively, p = .0173) and greater improvement in ad hoc analysis of anxiety and mood-related behaviors on the Visual Analog Scale (minocycline: 5.26 cm ± 0.46 cm, placebo: 4.05 cm ± 0.46 cm; p = .0488). Side effects were not significantly different during the minocycline and placebo treatments. No serious adverse events occurred on minocycline. Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding, and preliminary efficacy analysis results known to investigators.
  
  
  CONCLUSIONS
  Minocycline treatment for 3 months in children with FXS resulted in greater global improvement than placebo. Treatment for 3 months appears safe; however, longer trials are indicated to further assess benefits, side effects, and factors associated with a clinical response to minocycline.
authors.affiliation: Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA 95817, USA. maryjacena.leigh@ucdmc.ucdavis.edu
authors.forename: Mary Jacena S
authors.initials: MJ
authors.lastname: Leigh
authors.forename: Danh V
authors.initials: DV
authors.lastname: Nguyen
authors.forename: Yi
authors.initials: Y
authors.lastname: Mu
authors.forename: Tri I
authors.initials: TI
authors.lastname: Winarni
authors.forename: Andrea
authors.initials: A
authors.lastname: Schneider
authors.forename: Tasleem
authors.initials: T
authors.lastname: Chechi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Polussa
authors.forename: Paul
authors.initials: P
authors.lastname: Doucet
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rivera
authors.forename: David
authors.initials: D
authors.lastname: Hessl
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005600:Fragile X Syndrome / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D007360:Intelligence / Q000187:drug effects; D008297:Male; D008911:Minocycline / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011581:Psychological Tests; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D008911:Minocycline