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

Study Overview
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Brief Summary
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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.

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

Conditions
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Down Syndrome

Intervention / Treatment
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* Drug: thyroid hormone and folinic acid


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thyroxin + folinic acid<br> | Drug: thyroid hormone and folinic acid<br>* thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules<br>|
| Active Comparator: Thyroxin+folinic acid placebo<br> | Drug: thyroid hormone and folinic acid<br>* thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules<br>|
| Active Comparator: Thyroxin placebo+ folinic acid<br> | Drug: thyroid hormone and folinic acid<br>* thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules<br>|
| Placebo Comparator: Thyroxin placebo+ folinic acid placebo<br> | Drug: thyroid hormone and folinic acid<br>* thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GMDS, Down syndrome, Young children, Psychomotor development, Thyroid hormone, Folinic acid, Psychometric tests, Griffiths, Genetic factors, Biochemical factors