E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-surgical hypothyroidism in substitutive therapy |
Ipotiroidismo post-chirurgico in terapia sostitutiva |
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E.1.1.1 | Medical condition in easily understood language |
Patients without thyroid that need to take thyroid hormones as a therapy |
Soggetti senza tiroide che devono assumere per bocca gli ormoni tiroidei mancanti |
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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 | 10036429 |
E.1.2 | Term | Postsurgical hypothyroidism |
E.1.2 | System Organ Class | 100000004863 |
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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 |
In hypothyroid patients, with no residual thyroid function (thyroidectomized), evaluation of peripheral tissues response to combined therapy with levothyroxine (LT4) and liothyronine (LT3), after partial substitution of ongoing LT4 therapy with personalized doses of LT4 and LT3, respecting its circadian rythmicit and the physiological ratio of T3/T4.
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In pazienti ipotiroidei con funzionalità tiroidea residua praticamente assente (tiroidectomizzati), valutare la risposta dei tessuti periferici alla somministrazione combinata di levotiroxina (LT4) e liotironina (LT3), sostituendo parzialmente la terapia in corso basata su solo LT4 con dosi personalizzate di LT4 e LT3, nel rispetto della ritmicità circadiana di quest’ultima e del fisiologico rapporto T3/T4.
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E.2.2 | Secondary objectives of the trial |
In hypothyroid patients, with no residual thyroid function (thyroidectomized), evaluation of metabolic modifications, quality of life and gene expression in response to combined therapy with levothyroxine (LT4) and liothyronine (LT3), after partial substitution of ongoing LT4 therapy with personalized doses of LT4 and LT3, respecting its circadian rythmicit and the physiological ratio of T3/T4.
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In pazienti ipotiroidei con funzionalità tiroidea residua praticamente assente (tiroidectomizzati), valutare le modificazioni metaboliche, della qualità di vita e dell'espressione di alcuni geni target, in risposta alla somministrazione combinata di levotiroxina (LT4) e liotironina (LT3), sostituendo parzialmente la terapia in corso basata su solo LT4 con dosi personalizzate di LT4 e LT3, nel rispetto della ritmicità circadiana di quest’ultima e del fisiologico rapporto T3/T4.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients older than 18, capable of consent, able to sign a written informed consent, able to understand and fill in an italian questionnaire; residual thyroid function nearly absent (thyroidectomized, with serum tireoglobulin < 0.2 ng/ml and negative anti-tireoglobulin antibodies , in order to avoid methodological measurement interference), well comopensated with LT4 (pills)substitutive therapy, at stable dose for at least 3 months. |
Pazienti di età superiore a 18 anni, capaci di intendere e di volere,in grado di firmare volontariamente un consenso informato, previamente approvato dal Comitato Etico di riferimento, prima dello svolgimento di qualsiasi procedura prevista nella conduzione dello studio; in grado di capire e compilare un questionario in italiano; con funzionalità tiroidea residua presumibilmente assente (sottoposti a tiroidectomia totale, con tireoglobulina sierica < 0.2 ng/ml e anticorpi anti-tireoglobulina negativi, al fine di evitare interferenze nella metodica di dosaggio della tireoglobulina), in buon compenso in corso di terapia sostitutiva con LT4 in compresse, a dose stabile da almeno 3 mesi. |
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E.4 | Principal exclusion criteria |
TSH-suppressive therapy, pregnancy, severe cardiac diseases, pituitary or adrenal untreated insufficiency, severe liver or kidney or bone disease, ongoing therapy with corticosteroids, amiodarone, colestiramine or iron, or with anti-absorptive drugs ongoing or in the previous 12 months, alcohol addiction, epilepsy. |
terapia TSH soppressiva, tireotossicosi, gravidanza, gravi patologie cardiache, insufficienza surrenalica non trattata, insufficienza ipofisaria non trattata, gravi patologie epatiche, renali o del metabolismo osseo; terapia con corticosteroidi, antiriassorbitivi ossei (in atto o nei 12 mesi precedenti), amiodarone, colestiramina o ferro; alcolismo; epilessia |
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E.5 End points |
E.5.1 | Primary end point(s) |
Peripheral tissues response to variations of fT3 and fT4, measured by tissue markers such as TSH, SHBG, total and LDL cholesterol, lipoprotein(a), osteocalcin,urinary N-telopeptide, ferritin, myoglobin, CK, G6PD, ACE. |
risposta tissutale alle variazioni dei livelli periferici di fT3 e fT4, misurabile valutando i livelli di noti marker tissutali di funzionalità tiroidea, quali, oltre al TSH, SHBG, colesterolo totale, colesterolo LDL, lipoproteina(a), osteocalcina, N-telopeptide urinario, ferritina, mioglobina, creatinkinasi, glucosio-6-fosfato deidrogenasi, ACE. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Metabolic modifications (body weight, BMI, body and bone composition with DEXA); quality of life assessment; variation in the expression of tissue specific miRNA, for example in the muscle, that change in response to different thyroid states; correlation between TSH, fT3 and/or fT4 and SNPs of genes (DIO1 and DIO2) involved in thyroid hormones metabolism. |
Modificazioni dello stato metabolico (peso, BMI, composizione corporea e ossea mediante densitometria ossea (DEXA)); modificazioni della qualità di vita; variazioni dell’espressione di miRNA tessuto-specifici, per esempio muscolari, che può variare a seconda dello stato tiroideo; correlazione tra i livelli di TSH, fT3 e/o fT4 e i polimorfismi di geni (DIO1 e DIO2) coinvolti nel metabolismo degli ormoni tiroidei. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
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
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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 | 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 |