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Influence of Initial Levothyroxine Dose on Neurodevelopmental and Growth Outcomes in Congenital Hypothyroidism

Primary Purpose

Congenital Hypothyroidism

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Levothyroxin
Sponsored by
Federico II University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congenital Hypothyroidism focused on measuring Neonatal screening, Levothyroxine treatment, Neurocognitive, Growth

Eligibility Criteria

3 Days - 29 Days (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Congenital Hypothyroidism diagnosed by neonatal screening program
  • Age less than 30 days at diagnosis
  • TSH value at confirmatory diagnosis above 30 mU/l
  • Caucasian ethnicity

Exclusion Criteria:

  • Prematurity
  • Major congenital malformations
  • Neonatal diseases
  • Chromosomopathies
  • Known maternal thyroid diseases

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Active Comparator

    Arm Label

    10-12.5 μg/kg/day of L-T4

    12.6-15 μg/kg/day of L-T4

    Arm Description

    Children with congenital hypothyroidism who received an initial L-T4 dose of 10-12.5 μg/kg/day.

    Children with congenital hypothyroidism who received an initial L-T4 dose of 12.6-15 μg/kg/day.

    Outcomes

    Primary Outcome Measures

    Neurodevelopmental outcomes
    Cognitive and behavioral assessment was performed using Wechsler Preschool and Primary scale of Intelligence (WIPPSI-III). The WIPPSI-III evaluates the intelligence of children between 2.6 and 7.3 years and provides a Total Intelligence Quotient, a Verbal Intelligence Quotient, a Performance Intelligence Quotient and a Processing Speed Quotient. Quotients > 85 are considered normal.
    Linear Growth
    Linear growth was evaluated periodically during the study through the measurement of length up to 3 years and height subsequently. Length and height were measured in centimeters and are expressed as standard deviation score.

    Secondary Outcome Measures

    Full Information

    First Posted
    May 4, 2022
    Last Updated
    May 7, 2022
    Sponsor
    Federico II University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05371262
    Brief Title
    Influence of Initial Levothyroxine Dose on Neurodevelopmental and Growth Outcomes in Congenital Hypothyroidism
    Official Title
    Evaluation of Long-term Benefit-risk Profile of Levothyroxine Treatment in Children With Congenital Hypothyroidism: Influence of Initial Levothyroxine Dose on Neurodevelopmental, Growth, Cardiovascular and Skeletal Outcomes
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2022
    Overall Recruitment Status
    Completed
    Study Start Date
    May 2011 (Actual)
    Primary Completion Date
    May 2018 (Actual)
    Study Completion Date
    May 2018 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Federico II University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The primary objective of this study is to evaluate the risk-benefit profile of long-term treatment of two different initials treatment schemes with L-T4 on the neurodevelopmental and auxological outcomes in children with congenital hypothyroidism, diagnosed by neonatal screening in order to find the best dose of initial thyroid hormone replacement to assure the best long-term developmental outcome without any adverse effects on auxological, cardiovascular and skeletal outcomes. The secondary objective of the study is to evaluate the role of other factors that, in addition to the initial L-T4 therapy,can influence long-term neurodevelopmental and auxological outcomes as well as the cardiovascular system and bone metabolism outcomes.
    Detailed Description
    Seventy-two neonates detected by the neonatal screening program for congenital hypothyroidism were randomly assigned to receive one of the two initial L-T4 replacement dose: Group A received an initial replacement dose of 10-12.5 mcg/kg/die and Group B received an initial replacement dose of 12.6-15 mcg/kg/die. The adequacy of treatment were monitored closely by clinical evaluation and regular measurement of FT4 and TSH. Cognitive development were evaluated through the Griffiths Mental Development Scales at the the age of 2 yeas. Cognitive and behavioural assessment at the age of 4 years were performed using the Wechsler Preschool and Primary scale of Intelligence. Growth were evaluate at the enrolment and at each visit. Skeletal maturation were evaluated at diagnosis and at the age of 1 and 4 years. At the age of 4 years a quantitative ultrasound measurements and cardiovascular evaluation were performed.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Congenital Hypothyroidism
    Keywords
    Neonatal screening, Levothyroxine treatment, Neurocognitive, Growth

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Model Description
    Children were randomly assigned to receive an initial L-T4 dose of 10-12.5 μg/kg/day (Group A) or 12.6-15 μg/kg/day (Group B). Randomization was designed according to a block scheme (8 blocks of 6 patients and 6 blocks of 4 patients which were randomly alternated) which guaranteed the frequency balance in the two groups during the enrolment without altering the causality of the assignment. Random allocation sequence was generated using the function sample in R statistical platform.
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    72 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    10-12.5 μg/kg/day of L-T4
    Arm Type
    Active Comparator
    Arm Description
    Children with congenital hypothyroidism who received an initial L-T4 dose of 10-12.5 μg/kg/day.
    Arm Title
    12.6-15 μg/kg/day of L-T4
    Arm Type
    Active Comparator
    Arm Description
    Children with congenital hypothyroidism who received an initial L-T4 dose of 12.6-15 μg/kg/day.
    Intervention Type
    Drug
    Intervention Name(s)
    Levothyroxin
    Other Intervention Name(s)
    L-T4
    Intervention Description
    Congenital hypothyroidism children received two different doses of levothyroxin within the recommended range to evaluate any differences in long-term outcomes.
    Primary Outcome Measure Information:
    Title
    Neurodevelopmental outcomes
    Description
    Cognitive and behavioral assessment was performed using Wechsler Preschool and Primary scale of Intelligence (WIPPSI-III). The WIPPSI-III evaluates the intelligence of children between 2.6 and 7.3 years and provides a Total Intelligence Quotient, a Verbal Intelligence Quotient, a Performance Intelligence Quotient and a Processing Speed Quotient. Quotients > 85 are considered normal.
    Time Frame
    At four years of age
    Title
    Linear Growth
    Description
    Linear growth was evaluated periodically during the study through the measurement of length up to 3 years and height subsequently. Length and height were measured in centimeters and are expressed as standard deviation score.
    Time Frame
    7-10 days after the start of treatment and at 1.5, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 months of life.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    3 Days
    Maximum Age & Unit of Time
    29 Days
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Congenital Hypothyroidism diagnosed by neonatal screening program Age less than 30 days at diagnosis TSH value at confirmatory diagnosis above 30 mU/l Caucasian ethnicity Exclusion Criteria: Prematurity Major congenital malformations Neonatal diseases Chromosomopathies Known maternal thyroid diseases
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Mariacarolina Salerno, Professor
    Organizational Affiliation
    Federico II University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    24446653
    Citation
    Leger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G, Polak M, Butler G; ESPE-PES-SLEP-JSPE-APEG-APPES-ISPAE; Congenital Hypothyroidism Consensus Conference Group. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab. 2014 Feb;99(2):363-84. doi: 10.1210/jc.2013-1891. Epub 2014 Jan 21.
    Results Reference
    background
    PubMed Identifier
    16740880
    Citation
    American Academy of Pediatrics; Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association; Brown RS; Public Health Committee, Lawson Wilkins Pediatric Endocrine Society; Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006 Jun;117(6):2290-303. doi: 10.1542/peds.2006-0915.
    Results Reference
    background
    PubMed Identifier
    19160309
    Citation
    Ng SM, Anand D, Weindling AM. High versus low dose of initial thyroid hormone replacement for congenital hypothyroidism. Cochrane Database Syst Rev. 2009 Jan 21;2009(1):CD006972. doi: 10.1002/14651858.CD006972.pub2.
    Results Reference
    background
    PubMed Identifier
    36133316
    Citation
    Esposito A, Vigone MC, Polizzi M, Wasniewska MG, Cassio A, Mussa A, Gastaldi R, Di Mase R, Vincenzi G, Pozzi C, Peroni E, Bravaccio C, Capalbo D, Bruzzese D, Salerno M. Effect of initial levothyroxine dose on neurodevelopmental and growth outcomes in children with congenital hypothyroidism. Front Endocrinol (Lausanne). 2022 Sep 5;13:923448. doi: 10.3389/fendo.2022.923448. eCollection 2022.
    Results Reference
    derived

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    Influence of Initial Levothyroxine Dose on Neurodevelopmental and Growth Outcomes in Congenital Hypothyroidism

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