HypothyroidismDEEPTYPENCT06566066
Register for Patients With Thyroid Hormone Resistance.
An observational study of Hypothyroidism and Global Developmental Delay, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial summary
Thyroid hormones (TH) play a pivotal role in the development and function of the mammalian brain. Patients with impaired thyroid hormone transport into the brain tissue or in the case of defective local thyroid hormone receptor (collectively referred to as thyroid hormone resistance) subsequently experience… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hypothyroidism, Global Developmental Delay, Intellectual Disability
- How many people
- 200 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jul 2021to 31 Jul 2029
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: * Patients with THRα deficiency => Patients in whom a coding or non-coding pathogenic mutation was found in the THRA-gene or its regulating genomic regions (e.g. enhancers, promoters) * Patients with MCT8 deficiency => Patients in whom a coding or non-coding pathogenic mutation was found in the SLC16A2-gene or its regulating genomic regions (e.g. enhancers, promoters)
Who may be able to join
- Presence of a coding or non-coding mutation in SLC16A2
- Presence of a coding or non-coding mutation in THRA
- Abnormal fT3/fT4 ratio in the serum
- Written informed consent of the caregivers for participation in the register study
Who cannot join
- Withdrawal of consent
- Correction/change of the molecular diagnosis
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
Charite - Universitaetsmedizin Berlin
Berlin, 13353
Nina M Wilpert, MD/PhD, +49 30 450 616207, nina-maria.wilpert@charite.de
Markus Schülke, MD, +49 30 4505 66112, markus.schuelke@charite.de
About this study
Official title: Deep Geno- and Phenotyping of Patients With Thyroid Hormone Resistance, a Register Study.
Thyroid hormones (TH) play a pivotal role in the development and function of the mammalian brain. Patients with impaired thyroid hormone transport into the brain tissue or in the case of defective local thyroid hormone receptor (collectively referred to as thyroid hormone resistance) subsequently experience psychomotor disabilities.
The "DEEPTYPE" registry has been established with the objective of intensifying the genotyping and, in particular, the neurological phenotyping of patients exhibiting deficiencies in either the thyroid hormone transporter (MCT8) or the thyroid hormone receptor alpha (THRα). The objective of this registry-based study is to enhance the diagnostic yield for MCT8 and THRα deficiencies by employing the serum fT3/fT4 ratio as a more sophisticated screening parameter. Furthermore, the investigators will study the genomic regulation of both genes and attempt to identify further coding and non-coding mutations that result in TH resistance. The patient registry "DEEPTYPE" will document the retrospective and prospective clinical data of identified children in a comprehensive manner. This will enable the identification of three key groups: (i) patients with non-coding mutations, (ii) patients with milder phenotypes presenting only with a subset of symptoms seen in both "classic" conditions, and (iii) patients who are ready for clinical trials.
Read the detailed description
Thyroid hormones (TH) are of vital importance in the development and functioning of the brain. A deficiency in fetal thyroid hormone (TH) supply has been linked to significant psychomotor retardation in children born in regions with inadequate iodine supply. Insufficient postnatal production of thyroid hormones (TH) can result in intellectual and motor disabilities. These can be prevented by L-thyroxine (T4) supplementation in children with congenital hypothyroidism immediately after birth.
However, in the event of impaired transport of thyroid hormones into the brain tissue or in the case of defective local thyroid hormone receptors, the cerebral action of these hormones is impeded despite the presence of a sufficient thyroid hormone production. Such conditions may result from mutations in either SLC16A2, which encodes the monocarboxylate transporter 8 (MCT8), or THRA, which codes for the thyroid hormone receptor alpha (THRα). THRα is widely expressed in the central nervous system (CNS). In both instances, the absence of local TH action results in severe intellectual disability, developmental delay, movement disorders, and decreased brain volumes. In contrast to the outcomes observed in cases of congenital hypothyroidism, treatment trials involving the substitution of TH were ineffective in preventing the neurological phenotype in these children.
The full genotypic and phenotypic spectrum of these children has yet to be explored. It is anticipated that both conditions will be significantly underdiagnosed, given that awareness of these differential diagnoses within the pediatric community remains limited. As the standard screening parameters, such as thyroid-stimulating hormone (TSH), are not altered, the condition is frequently overlooked and is most often only "accidentally" diagnosed through next-generation sequencing.
The sole endocrine irregularity is a relative elevation of 3,3',5-triiodothyronine (T3) in comparison to T4. However, this is not a parameter that is routinely measured. More often the concentrations of the free plasma concentrations of these hormones, e.g. fT3 and fT4, are measured.
To date, only patients with mutations in the coding regions of the respective loci have been described. It can be reasonably assumed that mutations in the non-coding regulatory regions will result in disruption of the tissue-specific TH action in the MCT8/THRα-deficient brain. Similarly, disruptions in gene expression resulting from mutant regulatory enhancer sequences have recently been identified in other endocrine disorders, including congenital diabetes and brain developmental disorders.
The objective of this study is to enhance the diagnostic yield for MCT8 and THRα deficiencies by employing the serum fT3/fT4 ratio as a potentially more sophisticated screening parameter. Furthermore, the investigators will study the genomic regulation of both genes. The patient registry "DEEPTYPE" will be used to comprehensively document retrospective and prospective clinical data of identified children with coding or non-coding mutations. This will enable the investigators to identify patients with non-coding mutations and discover patients with milder phenotypes presenting only with a subset of symptoms seen in both "classic" conditions.
- Conditions
- Hypothyroidism, Global Developmental Delay, Intellectual Disability, Dystonia, Muscle Hypotonia, Seizures
- Being tested
- no intervention
- Keywords
- Thyroid hormone, Thyroid hormone resistance, MCT8, SLC16A2, THRA deficiency, Myelination
- Medical subject headings
- Hypothyroidism, Learning Disabilities, Intellectual Disability, Dystonia, Muscle Hypotonia, Seizures, Allan-Herndon-Dudley syndrome, Microcephaly
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no interventionOther
Also called does not apply
register study without intervention
| Study group | Role | What they receive |
|---|---|---|
| Patients with mutations in SLC16A2 | Text Receives: Other: no intervention | |
| Patients with mutations in THRA | Text Receives: Other: no intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Description of infant motor and language development
Bayley Scales of Infant and Toddler Development III => (Units on a Scale and Sum Score)
Measured: 5 years
Description of neurological abnormalities
Hammersmith Infant Neurological Examination (HINE) => (Units on a Scale and Sum Score)
Measured: 5 years
Description of motor development
Gross Motor Function Measure (GMFM-88) => (Units on a Scale and Sum Score)
Measured: 5 years
Secondary outcomes (17)
body weight
kilograms
Measured: 5 years
body length
centimeters
Measured: 5 years
head circumference
centimeters
Measured: 5 years
Reponse to therapies (e.g. Triac, DIPTA, levodopa/carbidopa)
Recording of responses to standard and experimental therapies
Measured: 5 years
T3
microgram per liter
Measured: 5 years
T4
microgram per liter
Measured: 5 years
fT3
microgram per liter
Measured: 5 years
fT4
microgram per liter
Measured: 5 years
TSH
mU per litre
Measured: 5 years
CSF fT3
microgram per liter
Measured: 5 years
CSF fT4
microgram per liter
Measured: 5 years
CSF levodopa
micromol/l
Measured: 5 years
CSF homovanillic acid (HVA)
micromol/l
Measured: 5 years
CSF 5-hydroxyindoleacetic acid (5-HIAA)
micromol/l
Measured: 5 years
Quantification of dystonia
Burke-Fahn-Marsden Dystonia Rating Scale => (Units on a Scale and Sum Score)
Measured: 5 years
Quantification of parkinsonism in children
Parkinsonism Dystonia Scale for Infants and Young Children => (Units on a Scale and Sum Score)
Measured: 5 years
Quanitification of cerebral palys symptomes
Cerebral Palsy Child Health Index of Life with Disabilities => (Units on a Scale and Sum Score)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2024
- Study start1 Jul 2021
- Primary completion14 Jul 2029 (estimated)
- Study completion31 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for HypothyroidismStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Other
- Enrolment
- 200 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Markus Schuelke, M.D., Charite University, Berlin, Germany
- Investigators
- Heiko Krude, MD, Principal investigator, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06566066
- Sponsor's protocol ID
- EA2_026_20
- Acronym
- DEEPTYPE
- Status last verified
- Aug 2024
- First submitted
- 11 Aug 2024
- Last updated
- 22 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Wilpert NM, Krueger M, Opitz R, Sebinger D, Zschunke S, Mages B, Schulz A, Spranger J, Wirth EK, Stachelscheid H, Mergenthaler P, Vajkoczy P, Krude H, Kuhnen P, Bechmann I, Biebermann H. Spatiotemporal Changes of Cerebral Monocarboxylate Transporter 8 Expression. Thyroid. 2020 Sep;30(9):1366-1383. doi: 10.1089/thy.2019.0544. Epub 2020 Apr 17.
PubMed 32143555Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MH, Kuiper GG, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet. 2004 Oct 16-22;364(9443):1435-7. doi: 10.1016/S0140-6736(04)17226-7.
PubMed 15488219Remerand G, Boespflug-Tanguy O, Tonduti D, Touraine R, Rodriguez D, Curie A, Perreton N, Des Portes V, Sarret C; RMLX/AHDS Study Group. Expanding the phenotypic spectrum of Allan-Herndon-Dudley syndrome in patients with SLC16A2 mutations. Dev Med Child Neurol. 2019 Dec;61(12):1439-1447. doi: 10.1111/dmcn.14332. Epub 2019 Aug 13.
PubMed 31410843Groeneweg S, Peeters RP, Moran C, Stoupa A, Auriol F, Tonduti D, Dica A, Paone L, Rozenkova K, Malikova J, van der Walt A, de Coo IFM, McGowan A, Lyons G, Aarsen FK, Barca D, van Beynum IM, van der Knoop MM, Jansen J, Manshande M, Lunsing RJ, Nowak S, den Uil CA, Zillikens MC, Visser FE, Vrijmoeth P, de Wit MCY, Wolf NI, Zandstra A, Ambegaonkar G, Singh Y, de Rijke YB, Medici M, Bertini ES, Depoorter S, Lebl J, Cappa M, De Meirleir L, Krude H, Craiu D, Zibordi F, Oliver Petit I, Polak M, Chatterjee K, Visser TJ, Visser WE. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019 Sep;7(9):695-706. doi: 10.1016/S2213-8587(19)30155-X. Epub 2019 Jul 31.
PubMed 31377265Groeneweg S, van Geest FS, Abaci A, Alcantud A, Ambegaonkar GP, Armour CM, Bakhtiani P, Barca D, Bertini ES, van Beynum IM, Brunetti-Pierri N, Bugiani M, Cappa M, Cappuccio G, Castellotti B, Castiglioni C, Chatterjee K, de Coo IFM, Coutant R, Craiu D, Crock P, DeGoede C, Demir K, Dica A, Dimitri P, Dolcetta-Capuzzo A, Dremmen MHG, Dubey R, Enderli A, Fairchild J, Gallichan J, George B, Gevers EF, Hackenberg A, Halasz Z, Heinrich B, Huynh T, Klosowska A, van der Knaap MS, van der Knoop MM, Konrad D, Koolen DA, Krude H, Lawson-Yuen A, Lebl J, Linder-Lucht M, Lorea CF, Lourenco CM, Lunsing RJ, Lyons G, Malikova J, Mancilla EE, McGowan A, Mericq V, Lora FM, Moran C, Muller KE, Oliver-Petit I, Paone L, Paul PG, Polak M, Porta F, Poswar FO, Reinauer C, Rozenkova K, Menevse TS, Simm P, Simon A, Singh Y, Spada M, van der Spek J, Stals MAM, Stoupa A, Subramanian GM, Tonduti D, Turan S, den Uil CA, Vanderniet J, van der Walt A, Wemeau JL, Wierzba J, de Wit MY, Wolf NI, Wurm M, Zibordi F, Zung A, Zwaveling-Soonawala N, Visser WE. Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre cohort study. Lancet Diabetes Endocrinol. 2020 Jul;8(7):594-605. doi: 10.1016/S2213-8587(20)30153-4.
PubMed 32559475Tonduti D, Vanderver A, Berardinelli A, Schmidt JL, Collins CD, Novara F, Genni AD, Mita A, Triulzi F, Brunstrom-Hernandez JE, Zuffardi O, Balottin U, Orcesi S. MCT8 deficiency: extrapyramidal symptoms and delayed myelination as prominent features. J Child Neurol. 2013 Jun;28(6):795-800. doi: 10.1177/0883073812450944. Epub 2012 Jul 17.
PubMed 22805248Masnada S, Sarret C, Antonello CE, Fadilah A, Krude H, Mura E, Mordekar S, Nicita F, Olivotto S, Orcesi S, Porta F, Remerand G, Siri B, Wilpert NM, Amir-Yazdani P, Bertini E, Schuelke M, Bernard G, Boespflug-Tanguy O, Tonduti D. Movement disorders in MCT8 deficiency/Allan-Herndon-Dudley Syndrome. Mol Genet Metab. 2022 Jan;135(1):109-113. doi: 10.1016/j.ymgme.2021.12.003. Epub 2021 Dec 16.
PubMed 34969638Wilpert NM, Tonduti D, Vaia Y, Krude H, Sarret C, Schuelke M. Establishing Patient-Centered Outcomes for MCT8 Deficiency: Stakeholder Engagement and Systematic Literature Review. Neuropsychiatr Dis Treat. 2023 Oct 20;19:2195-2216. doi: 10.2147/NDT.S379703. eCollection 2023.
PubMed 37881807
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deep Geno- and Phenotyping of Patients With Thyroid Hormone Resistance, a Register Study.
- ClinicalTrials.gov ID
- NCT06566066
- Acronym / sponsor ID
- DEEPTYPE / EA2_026_20
- Conditions
- Hypothyroidism, Global Developmental Delay, Intellectual Disability, Dystonia, Muscle Hypotonia, Seizures
- Keywords
- Thyroid hormone, Thyroid hormone resistance, MCT8, SLC16A2, THRA deficiency, Myelination
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 14 Jul 2029 (estimated)
- Study completion
- 31 Jul 2029 (estimated)
- First posted
- 22 Aug 2024 (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.
Thyroid hormones (TH) play a pivotal role in the development and function of the mammalian brain. Patients with impaired thyroid hormone transport into the brain tissue or in the case of defective local thyroid hormone receptor (collectively referred to as thyroid hormone resistance) subsequently experience psychomotor disabilities.
The "DEEPTYPE" registry has been established with the objective of intensifying the genotyping and, in particular, the neurological phenotyping of patients exhibiting deficiencies in either the thyroid hormone transporter (MCT8) or the thyroid hormone receptor alpha (THRα). The objective of this registry-based study is to enhance the diagnostic yield for MCT8 and THRα deficiencies by employing the serum fT3/fT4 ratio as a more sophisticated screening parameter. Furthermore, the investigators will study the genomic regulation of both genes and attempt to identify further coding and non-coding mutations that result in TH resistance. The patient registry "DEEPTYPE" will document the retrospective and prospective clinical data of identified children in a comprehensive manner. This will enable the identification of three key groups: (i) patients with non-coding mutations, (ii) patients with milder phenotypes presenting only with a subset of symptoms seen in both "classic" conditions, and (iii) patients who are ready for clinical trials.
Detailed description
Thyroid hormones (TH) are of vital importance in the development and functioning of the brain. A deficiency in fetal thyroid hormone (TH) supply has been linked to significant psychomotor retardation in children born in regions with inadequate iodine supply. Insufficient postnatal production of thyroid hormones (TH) can result in intellectual and motor disabilities. These can be prevented by L-thyroxine (T4) supplementation in children with congenital hypothyroidism immediately after birth.
However, in the event of impaired transport of thyroid hormones into the brain tissue or in the case of defective local thyroid hormone receptors, the cerebral action of these hormones is impeded despite the presence of a sufficient thyroid hormone production. Such conditions may result from mutations in either SLC16A2, which encodes the monocarboxylate transporter 8 (MCT8), or THRA, which codes for the thyroid hormone receptor alpha (THRα). THRα is widely expressed in the central nervous system (CNS). In both instances, the absence of local TH action results in severe intellectual disability, developmental delay, movement disorders, and decreased brain volumes. In contrast to the outcomes observed in cases of congenital hypothyroidism, treatment trials involving the substitution of TH were ineffective in preventing the neurological phenotype in these children.
The full genotypic and phenotypic spectrum of these children has yet to be explored. It is anticipated that both conditions will be significantly underdiagnosed, given that awareness of these differential diagnoses within the pediatric community remains limited. As the standard screening parameters, such as thyroid-stimulating hormone (TSH), are not altered, the condition is frequently overlooked and is most often only "accidentally" diagnosed through next-generation sequencing.
The sole endocrine irregularity is a relative elevation of 3,3',5-triiodothyronine (T3) in comparison to T4. However, this is not a parameter that is routinely measured. More often the concentrations of the free plasma concentrations of these hormones, e.g. fT3 and fT4, are measured.
To date, only patients with mutations in the coding regions of the respective loci have been described. It can be reasonably assumed that mutations in the non-coding regulatory regions will result in disruption of the tissue-specific TH action in the MCT8/THRα-deficient brain. Similarly, disruptions in gene expression resulting from mutant regulatory enhancer sequences have recently been identified in other endocrine disorders, including congenital diabetes and brain developmental disorders.
The objective of this study is to enhance the diagnostic yield for MCT8 and THRα deficiencies by employing the serum fT3/fT4 ratio as a potentially more sophisticated screening parameter. Furthermore, the investigators will study the genomic regulation of both genes. The patient registry "DEEPTYPE" will be used to comprehensively document retrospective and prospective clinical data of identified children with coding or non-coding mutations. This will enable the investigators to identify patients with non-coding mutations and discover patients with milder phenotypes presenting only with a subset of symptoms seen in both "classic" conditions.
Study design
- Observational model
- Case only
- Time perspective
- Other
- Target follow-up
- 5 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with mutations in SLC16A2 | – | Other: no interventionText |
| Patients with mutations in THRA | – | Other: no interventionText |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- * Patients with THRα deficiency => Patients in whom a coding or non-coding pathogenic mutation was found in the THRA-gene or its regulating genomic regions (e.g. enhancers, promoters) * Patients with MCT8 deficiency => Patients in whom a coding or non-coding pathogenic mutation was found in the SLC16A2-gene or its regulating genomic regions (e.g. enhancers, promoters)
Key inclusion criteria (4 listed)
- Presence of a coding or non-coding mutation in SLC16A2
- Presence of a coding or non-coding mutation in THRA
- Abnormal fT3/fT4 ratio in the serum
- Written informed consent of the caregivers for participation in the register study
Key exclusion criteria (2 listed)
- Withdrawal of consent
- Correction/change of the molecular diagnosis
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 |
|---|---|---|
| no interventionAlso: does not applyregister study without intervention | Other | Patients with mutations in SLC16A2, Patients with mutations in THRA |
Primary outcome
Description of infant motor and language development
Time frame: 5 years
Bayley Scales of Infant and Toddler Development III => (Units on a Scale and Sum Score)
Description of neurological abnormalities
Time frame: 5 years
Hammersmith Infant Neurological Examination (HINE) => (Units on a Scale and Sum Score)
Description of motor development
Time frame: 5 years
Gross Motor Function Measure (GMFM-88) => (Units on a Scale and Sum Score)
17 secondary outcomes
body weight
Time frame: 5 years
body length
Time frame: 5 years
head circumference
Time frame: 5 years
Reponse to therapies (e.g. Triac, DIPTA, levodopa/carbidopa)
Time frame: 5 years
T3
Time frame: 5 years
T4
Time frame: 5 years
fT3
Time frame: 5 years
fT4
Time frame: 5 years
TSH
Time frame: 5 years
CSF fT3
Time frame: 5 years
CSF fT4
Time frame: 5 years
CSF levodopa
Time frame: 5 years
CSF homovanillic acid (HVA)
Time frame: 5 years
CSF 5-hydroxyindoleacetic acid (5-HIAA)
Time frame: 5 years
Quantification of dystonia
Time frame: 5 years
Quantification of parkinsonism in children
Time frame: 5 years
Quanitification of cerebral palys symptomes
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2024.
- Background: PubMed 32143555Wilpert NM, Krueger M, Opitz R, Sebinger D, Zschunke S, Mages B, Schulz A, Spranger J, Wirth EK, Stachelscheid H, Mergenthaler P, Vajkoczy P, Krude H, Kuhnen P, Bechmann I, Biebermann H. Spatiotemporal Changes of Cerebral Monocarboxylate Transporter 8 Expression. Thyroid. 2020 Sep;30(9):1366-1383. doi: 10.1089/thy.2019.0544. Epub 2020 Apr 17.
- Background: PubMed 15488219Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MH, Kuiper GG, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet. 2004 Oct 16-22;364(9443):1435-7. doi: 10.1016/S0140-6736(04)17226-7.
- Background: PubMed 31410843Remerand G, Boespflug-Tanguy O, Tonduti D, Touraine R, Rodriguez D, Curie A, Perreton N, Des Portes V, Sarret C; RMLX/AHDS Study Group. Expanding the phenotypic spectrum of Allan-Herndon-Dudley syndrome in patients with SLC16A2 mutations. Dev Med Child Neurol. 2019 Dec;61(12):1439-1447. doi: 10.1111/dmcn.14332. Epub 2019 Aug 13.
- Background: PubMed 31377265Groeneweg S, Peeters RP, Moran C, Stoupa A, Auriol F, Tonduti D, Dica A, Paone L, Rozenkova K, Malikova J, van der Walt A, de Coo IFM, McGowan A, Lyons G, Aarsen FK, Barca D, van Beynum IM, van der Knoop MM, Jansen J, Manshande M, Lunsing RJ, Nowak S, den Uil CA, Zillikens MC, Visser FE, Vrijmoeth P, de Wit MCY, Wolf NI, Zandstra A, Ambegaonkar G, Singh Y, de Rijke YB, Medici M, Bertini ES, Depoorter S, Lebl J, Cappa M, De Meirleir L, Krude H, Craiu D, Zibordi F, Oliver Petit I, Polak M, Chatterjee K, Visser TJ, Visser WE. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019 Sep;7(9):695-706. doi: 10.1016/S2213-8587(19)30155-X. Epub 2019 Jul 31.
- Background: PubMed 32559475Groeneweg S, van Geest FS, Abaci A, Alcantud A, Ambegaonkar GP, Armour CM, Bakhtiani P, Barca D, Bertini ES, van Beynum IM, Brunetti-Pierri N, Bugiani M, Cappa M, Cappuccio G, Castellotti B, Castiglioni C, Chatterjee K, de Coo IFM, Coutant R, Craiu D, Crock P, DeGoede C, Demir K, Dica A, Dimitri P, Dolcetta-Capuzzo A, Dremmen MHG, Dubey R, Enderli A, Fairchild J, Gallichan J, George B, Gevers EF, Hackenberg A, Halasz Z, Heinrich B, Huynh T, Klosowska A, van der Knaap MS, van der Knoop MM, Konrad D, Koolen DA, Krude H, Lawson-Yuen A, Lebl J, Linder-Lucht M, Lorea CF, Lourenco CM, Lunsing RJ, Lyons G, Malikova J, Mancilla EE, McGowan A, Mericq V, Lora FM, Moran C, Muller KE, Oliver-Petit I, Paone L, Paul PG, Polak M, Porta F, Poswar FO, Reinauer C, Rozenkova K, Menevse TS, Simm P, Simon A, Singh Y, Spada M, van der Spek J, Stals MAM, Stoupa A, Subramanian GM, Tonduti D, Turan S, den Uil CA, Vanderniet J, van der Walt A, Wemeau JL, Wierzba J, de Wit MY, Wolf NI, Wurm M, Zibordi F, Zung A, Zwaveling-Soonawala N, Visser WE. Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre cohort study. Lancet Diabetes Endocrinol. 2020 Jul;8(7):594-605. doi: 10.1016/S2213-8587(20)30153-4.
- Background: PubMed 22805248Tonduti D, Vanderver A, Berardinelli A, Schmidt JL, Collins CD, Novara F, Genni AD, Mita A, Triulzi F, Brunstrom-Hernandez JE, Zuffardi O, Balottin U, Orcesi S. MCT8 deficiency: extrapyramidal symptoms and delayed myelination as prominent features. J Child Neurol. 2013 Jun;28(6):795-800. doi: 10.1177/0883073812450944. Epub 2012 Jul 17.
- Results publication: PubMed 34969638Masnada S, Sarret C, Antonello CE, Fadilah A, Krude H, Mura E, Mordekar S, Nicita F, Olivotto S, Orcesi S, Porta F, Remerand G, Siri B, Wilpert NM, Amir-Yazdani P, Bertini E, Schuelke M, Bernard G, Boespflug-Tanguy O, Tonduti D. Movement disorders in MCT8 deficiency/Allan-Herndon-Dudley Syndrome. Mol Genet Metab. 2022 Jan;135(1):109-113. doi: 10.1016/j.ymgme.2021.12.003. Epub 2021 Dec 16.
- Results publication: PubMed 37881807Wilpert NM, Tonduti D, Vaia Y, Krude H, Sarret C, Schuelke M. Establishing Patient-Centered Outcomes for MCT8 Deficiency: Stakeholder Engagement and Systematic Literature Review. Neuropsychiatr Dis Treat. 2023 Oct 20;19:2195-2216. doi: 10.2147/NDT.S379703. eCollection 2023.
- Individual participant dataSharing planned: Undecided
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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.
Heiko Krude, MD principal investigator
Charite University, Berlin, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypothyroidism and Global Developmental Delay, run by Charite University, Berlin, Germany at 1 site in Germany.
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 2 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: looking for participants now, as of the sponsor's last update on 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nina-Maria Wilpert (+49 30 450 ext. 616207, nina-maria.wilpert@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Description of infant motor and language development (time frame: 5 years). The study lists 3 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 NCT06566066, which also lists 8 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 22 Aug 2024.