E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In all cases of folate deficiency due to increased demand, poor absorption, inadequate dietary intake and reduced utilization of the vitamin in patients with viral liver cirrhosis. |
In tutti i casi di carenza folica per aumentata richiesta, insufficiente assorbimento, ridotta utilizzazione e insufficiente apporto dietetico della vitamina in pazienti con cirrosi epatica virale. |
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E.1.1.1 | Medical condition in easily understood language |
Deficiency of vitamin B group vitamins in patients with viral liver cirrhosis |
Carenza vitaminica di vitamine del gruppo B in pazienti con cirrosi virale |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047457 |
E.1.2 | Term | Viral hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047450 |
E.1.2 | Term | Viral hepatitis B |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
Evaluate, through a feasibility study, the pharmacokinetic characteristics in terms of absorption, distribution, metabolism of the active form of folate (5-MTHF) and of the inactive form (folic acid), in patients with viral liver cirrhosis related to severity of the disease. |
Valutare, tramite uno studio di fattibilità, le caratteristiche farmacocinetiche in termini di assorbimento, distribuzione, metabolismo della forma attiva dei folati (5-MTHF) rispetto alla forma inattiva (acido folico), in pazienti affetti da cirrosi epatica ad eziologia virale in relazione alla severità della malattia. |
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E.2.2 | Secondary objectives of the trial |
Evaluation of folates (total plasma, circulating and intraerythrocytic), hemoglobin, MCV and homocysteine in patients with liver cirrhosis after long-term (8 weeks) administration of 5-MTHF or folic acid.
Evaluation of 5-MTHF and folic acid pharmacokinetics in patients with liver cirrhosis in relation to severity of portal hypertension.
Evaluation of folate levels correlating with MTHFR possible mutation and concomitant therapies.
Evaluation of the correlation between values of hemoglobin, MCV and homocysteine with folate levels (total plasma, circulating and intraerythrocytic) in patients with liver cirrhosis. |
Valutazione dei livelli di folati (plasmatici totali, circolanti, intraeritrocitari), emoglobina, MCV e omocisteina nei pazienti con cirrosi epatica dopo somministrazione a lungo termine (8 settimane) di 5-MTHF o di acido folico.
Valutazione della farmacocinetica del 5-MTHF e dell’acido folico nei pazienti con cirrosi epatica in relazione alla severità dell’ipertensione portale.
Valutazione dei livelli di folati correlando con la possibile mutazione del MTHFR e le terapie concomitanti.
Valutazione della correlazione tra valori di emoglobina, MCV ed omocisteinemia con i livelli di folati (plasmatici totali, circolanti, intraeritrocitari) nei pazienti con cirrosi epatica. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with confirmed diagnosis of liver cirrhosis with viral etiology Age between 18 and 70 years Consent to participate in the study and willingness to submit to visits by the Protocol |
Pazienti con diagnosi accertata di cirrosi epatica ad eziologia virale Età compresa fra 18 e 70 anni Consenso alla partecipazione allo studio e disponibilità a sottoporsi alle visite definite dal protocollo |
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E.4 | Principal exclusion criteria |
Women who are pregnant or lactating Presence of cancer at enrollment or within five years preceding Presence of gastrointestinal bleeding or episodes that occurred in the four weeks prior to enrollment transplant patients Patients who have ongoing treatment with immunosuppressive or interferon Patients with a BMI more than 30 or less than 18 Patients in chronic therapy with folate, or medications / supplements containing B vitamins |
Donne in stato di gravidanza o in fase di allattamento Presenza di neoplasie al momento dell’arruolamento o nei cinque anni precedenti Presenza di emorragia gastrointestinale o episodi occorsi nelle quattro settimane precedenti all’arruolamento Pazienti trapiantati Pazienti che abbiano terapie in atto con trattamenti immunosoppressivi o interferone Pazienti con BMI maggiore di 30 o minore di 18 Pazienti in terapia cronica con folati, o farmaci / integratori contenenti vitamine del gruppo B |
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluate, through a feasibility study, the pharmacokinetic characteristics in terms of absorption, distribution, metabolism of the active form of folate (5-MTHF) and of the inactive form (folic acid), in patients with viral liver cirrhosis related to severity of the disease. |
Valutare, tramite uno studio di fattibilità, le caratteristiche farmacocinetiche in termini di assorbimento, distribuzione, metabolismo della forma attiva dei folati (5-MTHF) rispetto alla forma inattiva (acido folico), in pazienti affetti da cirrosi epatica ad eziologia virale in relazione alla severità della malattia. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After single dose administration, in the following 24 hours |
Dopo somminstrazione di singola dose, nelle 24 ore successive |
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E.5.2 | Secondary end point(s) |
Evaluation of folates (total plasma, circulating and intraerythrocytic), hemoglobin, MCV and homocysteine in patients with liver cirrhosis after long-term (8 weeks) administration of 5-MTHF or folic acid.
Evaluation of 5-MTHF and folic acid pharmacokinetics in patients with liver cirrhosis in relation to severity of portal hypertension.
Evaluation of folate levels correlating with MTHFR possible mutation and concomitant therapies.
Evaluation of the correlation between values of hemoglobin, MCV and homocysteine with folate levels (total plasma, circulating and intraerythrocytic) in patients with liver cirrhosis. |
Valutazione dei livelli di folati (plasmatici totali, circolanti, intraeritrocitari), emoglobina, MCV e omocisteina nei pazienti con cirrosi epatica dopo somministrazione a lungo termine (8 settimane) di 5-MTHF o di acido folico.
Valutazione della farmacocinetica del 5-MTHF e dell’acido folico nei pazienti con cirrosi epatica in relazione alla severità dell’ipertensione portale.
Valutazione dei livelli di folati correlando con la possibile mutazione del MTHFR e le terapie concomitanti.
Valutazione della correlazione tra valori di emoglobina, MCV ed omocisteinemia con i livelli di folati (plasmatici totali, circolanti, intraeritrocitari) nei pazienti con cirrosi epatica. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline, in the 24 hours following one single dose administration, and after 8 weeks of long-term administration |
Alla visita basale, dopo somminstrazione di singola dose (nelle 24 ore successive) e dopo 8 settimane di trattamento continuativo |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
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 | 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 | 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.8.6 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 | 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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |