E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This therapuetical trial will be conducted in patient with the Allan-Herndon-Dudley Syndrome (AHDS), casued by mutations in the thyroid hormone transporter MCT8. This results in the characteristic clinical phenotype of severe psychomotor retardation due to local hypothyroidism in the brain, in combination with high serum T3 and high normal serum TSH levels that lead to local hyperthyroidism in tissues that do not dependent on MCT8, resulting in tachycardia, low body weight and muscle wasting. |
Lo studio sarà condotto su pazienti con la sindrome di Allan-Herndon-Dudley (AHDS) dovuta a mutazione del trasportatore degli ormoni tiroidei MCT8. Il fenotipo clinico della AHDS è caratterizzato da un severo ritardo psicomotorio dovuto al deficit cerebrale di ormoni tiroidei. Ciò si associa alti livelli serici di T3 e normali livelli di TSH tali da determinare una situazione di disfunzione tissutale periferica degli ormoni tiroidei con conseguente tachicardia, basso peso, atrofia muscolare. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with a mutation in the thyroid hormone transporter MCT8, resulting in severe psychomotor retardation and abnormal thyroid hormone values in the blood. |
Pazienti con una mutazione del trasportatore degli ormoni tiroidei (MCT8), tale da determinare un grave ritardo psicomotrio ed un alterato profilo degli ormoni tiroidei nel sangue. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
(1) To determine the effect of Triac treatment on serum T3 and other TH levels.
(2) To determine the effect of Triac on the toxic effects of the hyperthyroid state in peripheral tissues.
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E.2.2 | Secondary objectives of the trial |
(1) To determine the effects of Triac treatment on the neurological phenotype.
(2) The registration of adverse event. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
clinical relevant mutation in the MCT8 gene leading to the clinical phenotype of AHDS |
rilevanti mutazioni cliniche del gene MCT8 caratterizzanti la sindrome di AHDS |
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E.4 | Principal exclusion criteria |
- Major illness or recent major surgery (within 4 weeks) unrelated to AHDS;
- Patients who are participating in ongoing RCTs of therapeutic interventions (including clinical trials of investigational medicinal products);
- Patients that have any major contra-indication for Triac treatment (severe cardiac decompensation (NYHA 4), coronary insufficiency, severe cardiac arrhytmias, Galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption). |
- gravi patologie o significativi interventi chirurgici (entro 4 settimane) non correlati con la sindrome di AHDS;
- pazienti che sono arruolati in altri studi clinici interventistici farmacologici in corso;
- pazienti che hanno gravi controindicazioni al trattamento con Triac (scompenso cardiaco grave (NYHA 4), insufficienza coronarica, grave aritmia cardiaca, intolleranza al galattosio, carenza di Lapp lattasi o malassorbimento di glucosio-galattosio). |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Serum TSH, T4, vrij T4, T3, rT3 and Triac levels
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
These primary endpoints will be evaluated at baseline (t=0) and after 1 year of Triac treatment.
To optimize titration of the Triac dose and prevent overtreatment, primary end-points will be evaluated with an expected average of 2 weeks during months 1-3 of the trial. During months 4-12 these parameters will be evaluated with an expected average of 6 weeks. |
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E.5.2 | Secondary end point(s) |
1) Body weight, blood pressure and heart rate.
2) Serum levels of markers that reflect peripheral thyroid hormone action: serum steroid hormone binding globuline (SHBG) and lipids (liver), serum beta Ctx and alkalisch phosphatase (bone) and serum kreatine kinase (muscle).
3) Motor function, using the Gross Motor Function Measure.
4) Cognitive function using the Bayley Scales of Infant Development III, or Wechsler Preschool and Primary Scale of Intelligence II.
5) Adaptive behavior measured by the Vineland adaptive behavior scale.
6) Basal Metabolic Rate (BMR) using Doubly labeled Water (DLW).
7) The frequency and nature of adverse events. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secundary end points 1-3 will will be evaluated at baseline (t=0) and after 1 year of Triac treatment.
To optimize titration of the Triac dose and prevent overtreatment, these end points will also be evaluated with an expected average of 2 weeks during months 1-3 of the trial. During months 4-12 these parameters will be evaluated with an expected average of 6 weeks.
End points 3), 4) and 5) will be evaluated at baseline and after 1 year of Triac treatment.
Point 6) will be evaluated during the whole study period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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the end of the trial is defined as the date of the last investigational visit for the last patient undergoing protocol treatment. |
Lo studio terminerà con l'ultima visita dell'ultimo paziente. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |