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