Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children

Down Syndrome Clinical Trial

— ACTHYF  

Official title:

Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01576705
• Other study ID #: IJL-AFHT-TH10
• Status: Completed
• Phase: Phase 3
• Start date: April 2, 2012
• Est. completion date: December 14, 2017

Study information

• Verified date: December 2019
• Source: Institut Jerome Lejeune
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: December 14, 2017
• Est. primary completion date: December 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Months

Eligibility

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)

Related Conditions & MeSH terms

• Down Syndrome
• Syndrome

Intervention

Drug:
• thyroid hormone and folinic acid
thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules

Locations

Country	Name	City	State
France	Institut Jerome Lejeune	Paris

Sponsors (3)

Lead Sponsor	Collaborator
Institut Jerome Lejeune	Central Hospital, Nancy, France, Hôpital Cochin

Country where clinical trial is conducted

France, 

References & Publications (4)

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. — View 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. — View 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. — View 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. Epub 2005 Mar 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GMDS (Griffiths Mental Development Scale)	GMDS for testing and estimate babies psychomotor development from birth to 2 years trough six subscales : Locomotor, Personal-social, Hearing and language, Eye-Hand coordination, Performance.Sub- and General Quotients (GDQ) standard score are based on a mean of 100 and a standard deviation of 16. For children with delayed development, which is the case for children with Down Syndrome, Quotient tables could be not used because sub- and General quotient floors at 50. For each subscale, a raw score was derived from the contributing items. Total raw score was obtained by adding subscale raw scores. Sum of all subscale raw scores was converted into a development age using correspondence table. Subscale and global development quotients were computed by dividing the development age by the chronological age multiplied by 100. For preterm infants, chronological age was corrected taking into account the gestational term. Higher QD's scores show a better psychomotor development outcome	12 months
Secondary	BL (Brunet Lezine Revised Scale)	BL includes 4 subscales : Locomotor, Coordination, Language, Sociability. Subscale and global developpemental quotients were computed by dividing the developpemental age by the chronological age multiplied by 100. This kind of formula do not give a min-max outcome. Higher QD's scores show a better psychomotor developpement outcome.	12 months

External Links

•   Institut Jerome Lejeune