Congenital HypothyroidismPhase 4NCT05371262
Influence of Initial Levothyroxine Dose on Neurodevelopmental and Growth Outcomes in Congenital Hypothyroidism
A Phase 4 study testing Levothyroxin in people with Congenital Hypothyroidism, run by Federico II University.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 to 29 days
- Conditions the study is for
- Congenital Hypothyroidism
- What is being tested?
- Levothyroxin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- No sites listed yet
- Study dates
- May 2011to May 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 29 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- Prematurity
- Major congenital malformations
- Neonatal diseases
- Chromosomopathies
- Known maternal thyroid diseases
About this study
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
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.
Read the 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.
- Conditions
- Congenital Hypothyroidism
- Being tested
- Levothyroxin
- Keywords
- Neonatal screening, Levothyroxine treatment, Neurocognitive, Growth
- Medical subject headings
- Congenital Hypothyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxinDrug
Also called L-T4
Congenital hypothyroidism children received two different doses of levothyroxin within the recommended range to evaluate any differences in long-term outcomes.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Levothyroxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2022
- Study startMay 2011
- Primary completionMay 2018
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Congenital HypothyroidismStudies of the same condition, open and under way.
- More trials run by Federico II UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof.ssa Mariacarolina Salerno, Federico II University
- Investigators
- Mariacarolina Salerno, Professor, Principal investigator, Federico II University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05371262
- Sponsor's protocol ID
- FARM8A8FHP
- Status last verified
- May 2022
- First submitted
- 4 May 2022
- Last updated
- 12 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24446653American 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.
PubMed 16740880Ng 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.
PubMed 19160309Esposito 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.
PubMed 36133316
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05371262
- Acronym / sponsor ID
- FARM8A8FHP
- Conditions
- Congenital Hypothyroidism
- Keywords
- Neonatal screening, Levothyroxine treatment, Neurocognitive, Growth
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Study start
- May 2011 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 12 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| 10-12.5 μg/kg/day of L-T4 | Active comparator | Drug: LevothyroxinChildren with congenital hypothyroidism who received an initial L-T4 dose of 10-12.5 μg/kg/day. |
| 12.6-15 μg/kg/day of L-T4 | Active comparator | Drug: LevothyroxinChildren with congenital hypothyroidism who received an initial L-T4 dose of 12.6-15 μg/kg/day. |
Who may qualify
- Ages
- 3 to 29 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- Prematurity
- Major congenital malformations
- Neonatal diseases
- Chromosomopathies
- Known maternal thyroid diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevothyroxinAlso: L-T4Congenital hypothyroidism children received two different doses of levothyroxin within the recommended range to evaluate any differences in long-term outcomes. | Drug | 10-12.5 μg/kg/day of L-T4, 12.6-15 μg/kg/day of L-T4 |
Primary outcome
Neurodevelopmental outcomes
Time frame: 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.
Linear Growth
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2022.
- Background: PubMed 24446653Leger 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.
- Background: PubMed 16740880American 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.
- Background: PubMed 19160309Ng 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.
- Derived from this study: PubMed 36133316Esposito 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mariacarolina Salerno, Professor principal investigator
Federico II University
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Levothyroxin in people with Congenital Hypothyroidism, run by Federico II University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurodevelopmental outcomes (time frame: At four years of age). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05371262, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2022.