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

NCT ID: NCT01576705

Last Updated: 2020-05-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

175 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-04-02

Study Completion Date

2017-12-14

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.

Detailed Description

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Conditions

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Down Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Thyroxin + folinic acid

Group Type EXPERIMENTAL

thyroid hormone and folinic acid

Intervention Type DRUG

thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules

Thyroxin+folinic acid placebo

Group Type ACTIVE_COMPARATOR

thyroid hormone and folinic acid

Intervention Type DRUG

thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules

Thyroxin placebo+ folinic acid

Group Type ACTIVE_COMPARATOR

thyroid hormone and folinic acid

Intervention Type DRUG

thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules

Thyroxin placebo+ folinic acid placebo

Group Type PLACEBO_COMPARATOR

thyroid hormone and folinic acid

Intervention Type DRUG

thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules

Interventions

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thyroid hormone and folinic acid

thyroid hormone 25microg or placebo in tablets folinic acid 5 mg or placebo in capsules

Intervention Type DRUG

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)
Minimum Eligible Age

6 Months

Maximum Eligible Age

18 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hôpital Cochin

OTHER

Sponsor Role collaborator

Central Hospital, Nancy, France

OTHER

Sponsor Role collaborator

Institut Jerome Lejeune

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clotilde MIRCHER, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Jerome Lejeune, Paris, France

Franck STURTZ, MD, PhD

Role: STUDY_CHAIR

Department of Biochemistry and Molecular Genetics, Limoges University, Limoges, France

Locations

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Institut Jerome Lejeune

Paris, , France

Site Status

Countries

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France

References

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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.

Reference Type BACKGROUND
PMID: 20084109 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16889491 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15755847 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18296460 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34863019 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31281181 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.institutlejeune.org/

Institut Jerome Lejeune

Other Identifiers

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IJL-AFHT-TH10

Identifier Type: -

Identifier Source: org_study_id

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