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

Primary Purpose

Down Syndrome

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
thyroid hormone and folinic acid
Sponsored by
Institut Jerome Lejeune
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Down Syndrome focused on measuring Down syndrome, Young children, Psychomotor development, Thyroid hormone, Folinic acid, Psychometric tests, GMDS, Griffiths, Genetic factors, Biochemical factors

Eligibility Criteria

6 Months - 18 Months (Child)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Institut Jerome Lejeune

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Thyroxin + folinic acid

Thyroxin+folinic acid placebo

Thyroxin placebo+ folinic acid

Thyroxin placebo+ folinic acid placebo

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Full Information

First Posted
April 11, 2012
Last Updated
April 30, 2020
Sponsor
Institut Jerome Lejeune
Collaborators
Hôpital Cochin, Central Hospital, Nancy, France
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1. Study Identification

Unique Protocol Identification Number
NCT01576705
Brief Title
Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children
Acronym
ACTHYF
Official Title
Efficacy Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
April 2, 2012 (Actual)
Primary Completion Date
December 14, 2017 (Actual)
Study Completion Date
December 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Jerome Lejeune
Collaborators
Hôpital Cochin, Central Hospital, Nancy, France

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Down Syndrome
Keywords
Down syndrome, Young children, Psychomotor development, Thyroid hormone, Folinic acid, Psychometric tests, GMDS, Griffiths, Genetic factors, Biochemical factors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
175 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Thyroxin + folinic acid
Arm Type
Experimental
Arm Title
Thyroxin+folinic acid placebo
Arm Type
Active Comparator
Arm Title
Thyroxin placebo+ folinic acid
Arm Type
Active Comparator
Arm Title
Thyroxin placebo+ folinic acid placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
thyroid hormone and folinic acid
Intervention Description
thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules
Primary Outcome Measure Information:
Title
GMDS (Griffiths Mental Development Scale)
Description
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
Time Frame
12 months
Secondary Outcome Measure Information:
Title
BL (Brunet Lezine Revised Scale)
Description
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.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
18 Months
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clotilde MIRCHER, MD
Organizational Affiliation
Institut Jerome Lejeune, Paris, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Franck STURTZ, MD, PhD
Organizational Affiliation
Department of Biochemistry and Molecular Genetics, Limoges University, Limoges, France
Official's Role
Study Chair
Facility Information:
Facility Name
Institut Jerome Lejeune
City
Paris
ZIP/Postal Code
75015
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
20084109
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.
Results Reference
background
PubMed Identifier
16889491
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.
Results Reference
background
PubMed Identifier
15755847
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.
Results Reference
background
PubMed Identifier
18296460
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.
Results Reference
background
PubMed Identifier
34863019
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.
Results Reference
derived
PubMed Identifier
31281181
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.
Results Reference
derived
Links:
URL
http://www.institutlejeune.org/
Description
Institut Jerome Lejeune

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

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