Ignite Creation Date:
2024-05-05 @ 11:15 PM
Last Modification Date:
2024-10-26 @ 10:30 AM
Study NCT ID:
NCT01284049
Status:
COMPLETED
Last Update Posted:
2016-03-30
First Post:
2011-01-25
Brief Title:
Evaluation of OMEGAVEN 10 n-3 EFA Lipid Emulsion in Home Parenteral Nutrition-associated Liver Disease
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Study in Adults on HPN Who Have Developed PNALD Comparing Equivalent Doses of Two Lipid Emulsions OMEGAVEN 10 Enriched in n-3 EFA and a Standard Lipid Emulsion Intralipid 20 Not Enriched in n-3 EFA Vitamin E Supplement
Status:
COMPLETED
Status Verified Date:
2016-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MEGANORM
Brief Summary:
The objective of the study is to show that substitution of the usual lipid emulsion Intralipid 20 at a dose between 05 and 10 gkginfusion of parenteral nutrition n-6n-3 ratio 71 by an equivalent dose of 05 to 1 gkginfusion of another lipid emulsion OMEGAVEN 10 very rich in omega-3 n-3 n-6n-3 ratio 17 induces regression of PNALD due to the anti-inflammatory and anti-fibrotic effects of n-3 EFA
Regression of liver disease will be defined by normalization of the five liver function tests LFT conjugated bilirubin gamma GT alkaline phosphatase AST and ALT transaminases
Regression of liver disease will be defined by normalization of the five liver function tests LFT conjugated bilirubin gamma GT alkaline phosphatase AST and ALT transaminases
Detailed Description:
Background Parenteral nutrition-associated liver disease PNALD in the context of home parenteral nutrition for non-neoplastic chronic intestinal failure is the main metabolic complication of HPN as reflected by the combined liver and intestine transplantation rate of 45 in adults Prior to the onset of severe fibrosis the main basic histological lesions of cholangitis and steatosis evolve in parallel with abnormal liver function tests LFT the prevalence of which increases with the duration of HPN An n-6 polyunsaturated fatty acid lipid supplement based on soybean oil has been shown to be a major and independent determinant of PNALD at doses greater than 1 gkginfusion
Study objective to demonstrate that replacement of the usual lipid emulsion Intralipid 20 at a dose of 05 to 10 gkgPN infusion n-6n-3 ratio 7 by an equivalent dose of a new lipid emulsion OMEGAVEN 10 very rich in n-3 polyunsaturated fatty acids n-3n-6 ratio 7 induces regression of PNALD via the anti-inflammatory and anti-fibrotic effects of n-3 polyunsaturated fatty acids
Material and methods The treated population presents with severe chronic non-neoplastic intestinal failure rare disease requiring HPN in an accredited centre The median actuarial risk of PNALD is 50 after 5 years of HPN in adults PNALD will be defined on inclusion by 2 out of 5 abnormal LFTs ALT and AST transaminases conjugated bilirubin alkaline phosphatase and gamma-glutamyltranspeptidase This multicentre prospective randomized double-blind study will include patients with no organ failure other than intestinal failure and especially no signs of decompensated cirrhosis on abdominal Doppler ultrasound It will exclude unstable patients especially as a result of recent infection 6 weeks On inclusion HPN must have been administered for at least 12 weeks and after inclusion in the study 6 weeks of HPN will be devoted to standardization of inter-centre practices To be eligible for inclusion patients must have a predictable duration of HPN of more than 18 weeks with a degree of dependence 2 nutritional infusions per week
Other causes of liver disease will be excluded viral autoimmune alcohol hepatotoxic drugs biliary obstruction
The study duration per patient will be 22 weeks 6 weeks of standardization of HPN 12 weeks of treatment in one of the two arms and 4 weeks of follow-up HPN with Intralipid 20 will be continued unchanged in the HPN control arm and Intralipid 20 will be replaced by an equivalent dose 05 to 10 gkgInfusion of OMEGAVEN 10 up to a maximum dose of 40 mg per infusion due to formulation constraints in the interventional arm
The primary endpoint will be normalization of the 5 LFT parameters at the 12th week of treatment W18 According to published data the probability of normalization of LFT is less than 10 in the control arm and 50 in the treated arm A total of 32 patients must therefore be recruited in each arm to demonstrate a significant difference of normalization of LFT at the 12th week of treatment Chi-square or Fisher test p005 between the two groups This population could be recruited over a period of 18 months from the population treated in the three centres participating in the study Paris for the Ile-de-France region Lyon for the Rhone-Alpes region and Lille for the Nord-Pas de Calais region as these three centres follow 50 of the French adult HPN population representing 250 patients
A monthly safety study will be performed by clinical examination and determination of the usual laboratory parameters Fibrosis evaluated by Fibroscan in kilopascal and steatosis evaluated by abdominal Doppler ultrasound in three grades the relevant laboratory parameters reflecting the lipid supplements such as n-3 and n-6 essential fatty acids lipoperoxidation index explanatory factors of the harmful effect of n-6 polyunsaturated fatty acids and the protective effect of n-3 polyunsaturated fatty acids such as proinflammatory and anti-inflammatory cytokines and serum markers of hepatic fibrosis will be compared between the two arms at the beginning and at the end of treatment
Expected result This innovative prospective randomized study concerns PNALD which at the stage of cirrhosis in adults is responsible for the patients death in more than 22 of cases and requires combined liver and small intestine transplantation in 45 of cases The proposed therapeutic intervention prior to onset of severe PNALD is based on emerging rational hypotheses associated with a highly probable positive clinical expression
Study objective to demonstrate that replacement of the usual lipid emulsion Intralipid 20 at a dose of 05 to 10 gkgPN infusion n-6n-3 ratio 7 by an equivalent dose of a new lipid emulsion OMEGAVEN 10 very rich in n-3 polyunsaturated fatty acids n-3n-6 ratio 7 induces regression of PNALD via the anti-inflammatory and anti-fibrotic effects of n-3 polyunsaturated fatty acids
Material and methods The treated population presents with severe chronic non-neoplastic intestinal failure rare disease requiring HPN in an accredited centre The median actuarial risk of PNALD is 50 after 5 years of HPN in adults PNALD will be defined on inclusion by 2 out of 5 abnormal LFTs ALT and AST transaminases conjugated bilirubin alkaline phosphatase and gamma-glutamyltranspeptidase This multicentre prospective randomized double-blind study will include patients with no organ failure other than intestinal failure and especially no signs of decompensated cirrhosis on abdominal Doppler ultrasound It will exclude unstable patients especially as a result of recent infection 6 weeks On inclusion HPN must have been administered for at least 12 weeks and after inclusion in the study 6 weeks of HPN will be devoted to standardization of inter-centre practices To be eligible for inclusion patients must have a predictable duration of HPN of more than 18 weeks with a degree of dependence 2 nutritional infusions per week
Other causes of liver disease will be excluded viral autoimmune alcohol hepatotoxic drugs biliary obstruction
The study duration per patient will be 22 weeks 6 weeks of standardization of HPN 12 weeks of treatment in one of the two arms and 4 weeks of follow-up HPN with Intralipid 20 will be continued unchanged in the HPN control arm and Intralipid 20 will be replaced by an equivalent dose 05 to 10 gkgInfusion of OMEGAVEN 10 up to a maximum dose of 40 mg per infusion due to formulation constraints in the interventional arm
The primary endpoint will be normalization of the 5 LFT parameters at the 12th week of treatment W18 According to published data the probability of normalization of LFT is less than 10 in the control arm and 50 in the treated arm A total of 32 patients must therefore be recruited in each arm to demonstrate a significant difference of normalization of LFT at the 12th week of treatment Chi-square or Fisher test p005 between the two groups This population could be recruited over a period of 18 months from the population treated in the three centres participating in the study Paris for the Ile-de-France region Lyon for the Rhone-Alpes region and Lille for the Nord-Pas de Calais region as these three centres follow 50 of the French adult HPN population representing 250 patients
A monthly safety study will be performed by clinical examination and determination of the usual laboratory parameters Fibrosis evaluated by Fibroscan in kilopascal and steatosis evaluated by abdominal Doppler ultrasound in three grades the relevant laboratory parameters reflecting the lipid supplements such as n-3 and n-6 essential fatty acids lipoperoxidation index explanatory factors of the harmful effect of n-6 polyunsaturated fatty acids and the protective effect of n-3 polyunsaturated fatty acids such as proinflammatory and anti-inflammatory cytokines and serum markers of hepatic fibrosis will be compared between the two arms at the beginning and at the end of treatment
Expected result This innovative prospective randomized study concerns PNALD which at the stage of cirrhosis in adults is responsible for the patients death in more than 22 of cases and requires combined liver and small intestine transplantation in 45 of cases The proposed therapeutic intervention prior to onset of severe PNALD is based on emerging rational hypotheses associated with a highly probable positive clinical expression
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2010-022893-15 | EUDRACT_NUMBER | None | None |