@article{mircher_sacco_bouis_gallard_pichot_le galloudec_cieuta_marey_greiner-mahler_dorison_et al._2019, 
  title={Thyroid hormone and folinic acid in young children with Down syndrome: the phase 3 ACTHYF trial}, 
  volume={22}, 
  DOI={10.1038/s41436-019-0597-8}, 
  abstractNote={To determine whether folinic acid (FA) and thyroxine, in combination or alone, benefit psychomotor development in young patients with Down syndrome (DS).
The Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (ACTHYF) was a single-center, randomized, double-blind, placebo-controlled phase 3 trial in DS infants aged 6-18 months. Patients were randomly assigned to one of four treatments: placebo, folinic acid (FA), L-thyroxine, or FA+L-thyroxine, administered for 12 months. Randomization was done by age and sex. The primary endpoint was adjusted change from baseline in Griffiths Mental Development Scale global development quotient (GDQ) after 12 months.
Of 175 patients randomized, 143 completed the study. The modified intention-to-treat (mITT) population included all randomized patients who did not prematurely discontinue due to elevated baseline thyroid stimulating hormone (TSH). Baseline characteristics in the mITT were well balanced between groups, with reliable developmental assessment outcomes. Adjusted mean change in GDQ in the mITT showed similar decreases in all groups (placebo: -5.10 [95% confidence interval (CI) -7.84 to -2.37]; FA: -4.69 [95% CI -7.73 to -1.64]; L-thyroxine: -3.89 [95% CI -6.94 to -0.83]; FA+L-thyroxine: -3.86 [95% CI -6.67 to -1.06]), with no significant difference for any active treatment group versus placebo.
This trial does not support the hypotheses that thyroxine and/or folinic acid improve development of young children with DS or are synergistic. This trial is registered with ClinicalTrials.gov number, NCT01576705.}, 
  number={1}, 
  publisher={Springer Science and Business Media LLC}, 
  author={Mircher, Clotilde and Sacco, Silvia and Bouis, Charles and Gallard, Jennifer and Pichot, Aude and Le Galloudec, Eric and Cieuta, Cécile and Marey, Isabelle and Greiner-Mahler, Oliver and Dorison, Nathalie and et al.}, 
  year={2019}, 
  month={Jul}
  }