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

Sponsor
Federico II University (Other)
Overall Status
Completed
CT.gov ID
NCT05371262
Collaborator
(none)
72
Enrollment
2
Arms
84
Actual Duration (Months)

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
72 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention 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.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)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 1, 2011
Actual Primary Completion Date :
May 1, 2018
Actual Study Completion Date :
May 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 10-12.5 μg/kg/day of L-T4

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

Drug: Levothyroxin
Congenital hypothyroidism children received two different doses of levothyroxin within the recommended range to evaluate any differences in long-term outcomes.
Other Names:
  • L-T4

    		•
    Active Comparator: 12.6-15 μg/kg/day of L-T4

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

    Drug: Levothyroxin
    Congenital hypothyroidism children received two different doses of levothyroxin within the recommended range to evaluate any differences in long-term outcomes.
    Other Names:
  • L-T4

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Neurodevelopmental outcomes [At four years of age]

      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.

    2. Linear Growth [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.]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    3 Days to 29 Days
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Federico II University

    Investigators

    • Principal Investigator: Mariacarolina Salerno, Professor, Federico II University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Prof.ssa Mariacarolina Salerno, Associate Professor of Pediatrics, Head of Pediatric Endocrinology Unit, Federico II University
    ClinicalTrials.gov Identifier:
    NCT05371262
    Other Study ID Numbers:
    • FARM8A8FHP
    First Posted:
    May 12, 2022
    Last Update Posted:
    May 12, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Prof.ssa Mariacarolina Salerno, Associate Professor of Pediatrics, Head of Pediatric Endocrinology Unit, Federico II University
    Neonatal screening
    Levothyroxine treatment
    Neurocognitive
    Growth
    Additional relevant MeSH terms:
    Congenital Hypothyroidism
    Hypothyroidism

    Study Results

    No Results Posted as of May 12, 2022