E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary acquired hypothyroidism |
Ipotiroidismo primario acquisito |
|
E.1.1.1 | Medical condition in easily understood language |
Primary Hypothyroidism |
Ipotiroidismo primario |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000559 |
E.1.2 | Term | Acquired hypothyroidism |
E.1.2 | System Organ Class | 100000004860 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the effect of two different pharmaceutical forms of L-Thyroxine on the gut in terms of inflammatory parameters, gut absorption |
Lo scopo dello studio ¿ quello di testare gli effetti della L-T4, in due diverse formulazioni, a livello intestinale attraverso le modifiche dei parametri infiammatori e dell¿assorbimento intestinale |
|
E.2.2 | Secondary objectives of the trial |
- Evaluate the effect of two different pharmaceutical forms of L-Thyroxine on the gut in terms of modification of gut microbiota - Evaluate the effect of the disease (congenital Hypothyroidism) on the gut in terms of modification of gut microbiota, inflammatory parameters, gut absorption - Evaluate the incidence of celiac disease in hypothyroid patients |
- Testare gli effetti della L-T4, in due diverse formulazioni, a livello intestinale, attraverso le modifiche del microbiota - Caratterizzare l¿effetto dell¿ipotiroidismo sul microbiota intestinale, sui parametri infiammatori e dell¿assorbimento intestinale - Stimare l¿incidenza della celiachia nell¿intera coorte di pazienti ipotiroidei.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Children with primary acquired hypothyroidism that require Levothyroxine therapy (naïve patients, < 18 years) 2. Informed consent from parents and patient
|
1. Bambini ed adolescenti con ipotiroidismo primario acquisito con necessitante di terapia con L-T4, non trattati in precedenza e con età inferiore ai 18 anni al momento dell’arruolamento. 2. Ottenimento del consenso informato da parte del genitore e assenso del paziente.
|
|
E.4 | Principal exclusion criteria |
1. Age < 3 years 2. Patients with secondary hypothiroidism, euthyroid sick syndrome or thyroid ormone resistant 3. Patients with celiac diasease, type I diabetes or other known autoimmune diseases 4. Patients with genetic diseases or syndromes, such as Down, Williams-Beuren, Turner 5. Assumption of antibiotics, probiotics, prebiotics, or other medications that could affect the gut microbiota in the month before the beginning of the study 6. Gastrointestinal infectious diaseases in the month before the beginning of the study 7. Hypersensitivity to levothyroxine or any of the ingredients contained in the two pharmaceutical formulations 8. Untreated adrenal insufficiency, untreated pituitary insufficiency and untreated thyrotoxicosis. 9. Patients with cardiovascular disease 10. Patients who show with impaired pancreatic function measured using the assay in faecal fat (steatocrit) at the screeening visit |
1. Età inferiore a 3 anni di vita, per le difficoltà inerenti alla corretta conduzione dello studio e le loro particolarità fisiologiche e neuroevolutive. 2. Pazienti con ipotiroidismo secondario, con euthyroid sick syndrome o resistenza agli ormoni tiroidei saranno esclusi per i bias legati alle possibili associazioni di comorbilità ed ai farmaci possibilmente già assunti. 3. Pazienti con una diagnosi di malattia celiaca, diabete tipo I o altre malattie autoimmuni già diagnosticate al momento dell’ipotiroidismo. 4. Pazienti con patologie genetiche o sindromi, come la sindrome di Down, la sindrome di Turner, la sindrome di Williams-Beuren, conosciute essere associate ad un rischio maggiore di sviluppare malattia celiaca. 5. Assunzione di antibiotici, probiotici, prebiotici o qualsiasi altro trattamento medico influenzante il microbiota intestinale nel mese precedente l’inizio dello studio. 6. Malattie infettive gastrointestinali nel mese precedente l’inizio dello studio. 7. Ipersensibilità al principio attivo levotiroxina o a uno qualsiasi degli eccipienti contenuti nelle due formulazioni farmaceutiche 8. Insufficienza surrenalica non trattata, insufficienza ipofisaria non trattata e tireotossicosi non trattata. 9. Pazienti con patologie cardiovascolari 10. Pazienti che allo screening mostrano con alterazione della funzione pancreatica valutata mediante l’utilizzo del dosaggio dei grassi fecali (steatocrito).
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Calculate the difference in gut inflammation parameters (calprotectin, osteoprotegerin, S100-A12 protein) and gut absorption parameters among the two groups of patients at T6-T0 and T12-T6 |
Misurare le differenze tra i due gruppi al tempo T6 - T0 e le differenze intragruppo al tempo T12 – T6 (analisi prima-dopo) nei parametri infiammatori intestinali (livelli di calprotectina, osteoprotegerina, proteina S100-A12) e dei parametri dell’assorbimento intestinale (steatocrito) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Qualitative and quantitative (percentage) characterization of gut microbiota before the initiation of the therapy (T0); Difference in gut microbiota among hypothyroid patients (t0) and healthy patients (data from Human Microbiome Project); Estimate the incidence of positive patients to deamidated AGA T6, T12 e a T24 (follow-up); Evaluate gut inflammation (calprotectin, Osteoprotegerin and S100-A12 protein) and gut absorption (Steatocrit) parameters before the initiation of the therapy (T0); Calculate the difference in Shannon Index (index of diversity), Chao I (Species richness estimator), percentage of different species (OTU, operational taxonomic unit) among the two groups of patients at T6-T0 and T12-T6 |
Misurare al tempo T0 le caratteristiche del microbiota intestinale che saranno interamente riferibili allo stato di ipotiroidismo, in termini quantitativi (come percentuale) e qualitativi.; Differenze della tipizzazione del microbiota tra i soggetti ipotiroidei al T0 e quelli sani estrapolati dal Human Microbiome Project (HMP).
; Valutare l¿incidenza della positivit¿ degli AGA deaminati a T6, T12 e a T24 (follow-up).
; Misurare al tempo T0 i parametri infiammatori intestinali (livelli di calprotectina, osteoprotegerina, proteina S100-A12) e dei parametri dell¿assorbimento intestinale (steatocrito).; Misurare le differenze tra i due gruppi al tempo T6 - T0 e le differenze intragruppo al tempo T12 ¿ T6 rispetto a T6-T0 (analisi prima-dopo) nella percentuale di microrganismi presenti (Actinobacteria, Firmicutes, Bacteroidetes, proteobacteria. Le differenze saranno calcolate con lo Shannon Index e Chao I che riguardano rispettivamente la biodiversit¿ e la ricchezza delle specie presenti. Saranno assegnate delle OTU, operational taxonomic unit, che permetteranno attraverso l'analisi bioinformatica di conoscere che tipo di batteri sono presenti e in quale percentuale. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
BASELINE; BASELINE; BASELINE; BASELINE; 6-12 months |
TEMPO 0; TEMPO 0; TEMPO 0; TEMPO 0; 6-12 mesi |
|
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |