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

NCT05371262 | Completed Phase 4 DMC

• 1 other identifier: FARM8A8FHP
• Study Type: interventional
• Target: 72
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Congenital Hypothyroidism

Keywords

Neonatal screening; Levothyroxine treatment; Neurocognitive; Growth

Outcome Measures

Primary Outcomes (2)

• 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.

  At four years of age

• 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.

  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.

Study Arms (2)

10-12.5 μg/kg/day of L-T4

ACTIVE COMPARATOR

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

Drug: Levothyroxin

12.6-15 μg/kg/day of L-T4

ACTIVE COMPARATOR

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

Drug: Levothyroxin

Interventions

Levothyroxin DRUG

Congenital hypothyroidism children received two different doses of levothyroxin within the recommended range to evaluate any differences in long-term outcomes.

Also known as: L-T4

10-12.5 μg/kg/day of L-T4; 12.6-15 μg/kg/day of L-T4

Eligibility Criteria

• Age: 3 Days - 29 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Federico II University: lead

Related Publications (4)

• 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.

  PMID: 24446653 BACKGROUND

• 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.

  PMID: 16740880 BACKGROUND

• 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.

  PMID: 19160309 BACKGROUND

• 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.

  PMID: 36133316 DERIVED

MeSH Terms

Conditions

Congenital Hypothyroidism

Interventions

Thyroxine

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Hypothyroidism; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Mariacarolina Salerno, Professor

  Federico II University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics, Head of Pediatric Endocrinology Unit

Model Details: 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.

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 12, 2022
• Study Start: May 1, 2011
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: May 12, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share