Clinical trial NCT01576705: Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children
Official title: Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Down Syndrome
Keywords: Down syndrome
Young children
Psychomotor development
Thyroid hormone
Folinic acid
Psychometric tests
GMDS
Griffiths
Genetic factors
Biochemical factors
Lead sponsor: Institut Jerome Lejeune
Sponsor class: OTHER
Collaborators: name: Hôpital Cochin
name: Central Hospital, Nancy, France
First posted: 2012-04-12
Enrollment: 175
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluation of the following in very young children with Down syndrome:

* the efficacy of systematic treatment with L-thyroxine at controlled doses (clinically and by ultrasensitive thyreostimulating hormone (TSH) assay),
* the efficacy of systematic folinic acid treatment at a dose of 1 mg/kg/o.i.d,
* any interaction between these two treatments.


Eligibility criteria: Inclusion Criteria:

* patient with a karyotype demonstrating homogeneous, free or Robertsonian translocation trisomy 21
* patient having undergone a cardiac ultrasound not demonstrating any severe heart disease
* patient aged 6 to 18 months at inclusion

Exclusion Criteria:

* congenital hypothyroidism
* hypothyroidism demonstrated by laboratory tests (TSH \> 7mUI/l)
* presenting or having presented hyperthyroidism
* presenting or having presented leukaemia
* presenting or having presented West syndrome or any other form of epilepsy or unstable neurological disease
* presenting or having presented signs of central nervous system distress: stroke, postoperative hypoxia, meningitis)
* presenting severe heart disease on cardiac ultrasound, with haemodynamic effects
* presenting non-controlled cardiac arrhythmia
* Apgar \< 7 to 5 min at birth
* Gestational age \< 231 days (33 gestation weeks)

Primary outcomes:
measure: GMDS (Griffiths Mental Development Scale)
timeFrame: 12 months
Secondary outcomes:
measure: BL (Brunet Lezine Revised Scale)
timeFrame: 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Institut Jerome Lejeune
Study officials:
affiliation: Institut Jerome Lejeune, Paris, France
name: Clotilde MIRCHER, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Biochemistry and Molecular Genetics, Limoges University, Limoges, France
name: Franck STURTZ, MD, PhD
role: STUDY_CHAIR
References:
citation: Blehaut H, Mircher C, Ravel A, Conte M, de Portzamparc V, Poret G, de Kermadec FH, Rethore MO, Sturtz FG. Effect of leucovorin (folinic acid) on the developmental quotient of children with Down's syndrome (trisomy 21) and influence of thyroid status. PLoS One. 2010 Jan 11;5(1):e8394. doi: 10.1371/journal.pone.0008394.
citation: van Trotsenburg AS, Kempers MJ, Endert E, Tijssen JG, de Vijlder JJ, Vulsma T. Trisomy 21 causes persistent congenital hypothyroidism presumably of thyroidal origin. Thyroid. 2006 Jul;16(7):671-80. doi: 10.1089/thy.2006.16.671.
citation: van Trotsenburg AS, Vulsma T, van Rozenburg-Marres SL, van Baar AL, Ridder JC, Heymans HS, Tijssen JG, de Vijlder JJ. The effect of thyroxine treatment started in the neonatal period on development and growth of two-year-old Down syndrome children: a randomized clinical trial. J Clin Endocrinol Metab. 2005 Jun;90(6):3304-11. doi: 10.1210/jc.2005-0130. Epub 2005 Mar 8.
citation: Ellis JM, Tan HK, Gilbert RE, Muller DP, Henley W, Moy R, Pumphrey R, Ani C, Davies S, Edwards V, Green H, Salt A, Logan S. Supplementation with antioxidants and folinic acid for children with Down's syndrome: randomised controlled trial. BMJ. 2008 Mar 15;336(7644):594-7. doi: 10.1136/bmj.39465.544028.AE. Epub 2008 Feb 21.
citation: Sacco S, Bouis C, Gallard J, Pichot A, Blondiaux E, Marey I, Dorison N, Sturtz F, Cieuta-Walti C, Ravel A, Mircher C. Psychomotor development in infants and young children with Down syndrome-A prospective, repeated measure, post-hoc analysis. Am J Med Genet A. 2022 Mar;188(3):818-827. doi: 10.1002/ajmg.a.62587. Epub 2021 Dec 4.
citation: Mircher C, Sacco S, Bouis C, Gallard J, Pichot A, Le Galloudec E, Cieuta C, Marey I, Greiner-Mahler O, Dorison N, Gambarini A, Stora S, Durand S, Polak M, Baruchel A, Schlumberger E, Dewailly J, Azar-Kolakez A, Gueant-Rodriguez RM, Gueant JL, Borderie D, Bonnefont-Rousselot D, Blondiaux E, Ravel A, Sturtz FG. Thyroid hormone and folinic acid in young children with Down syndrome: the phase 3 ACTHYF trial. Genet Med. 2020 Jan;22(1):44-52. doi: 10.1038/s41436-019-0597-8. Epub 2019 Jul 8.