Effects of Preoperative Long-Term Immunonutrition in Patients Listed for Liver Transplantation

Study Overview
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Brief Summary
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Patients with endstage liver disease characteristically are malnourished which is associated with poor outcome. Formulas enriched with arginine,ω3 fatty acids, and nucleotides potentially improve their nutritional status. This randomized placebo-controlled double blind multicenter clinical trial with longterm preoperative supplementation with such an enriched formula will evaluate evaluate effects of such formulas on patients' quality of life, survival, and posttransplant morbidities.

Detailed Description
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Background. Patients with end stage liver disease characteristically are malnourished which is associated with poor outcome. Formulas enriched with arginine, ω-3 fatty acids, and nucleotides, immunonutrients, potentially improve their nutritional status. This study is designed to evaluate the clinical outcome of long-term immunonutrition of patients with end-stage liver disease while on the waiting list for liver transplantation. Methods / design. A randomized controlled double blind multi-center clinical trial with two parallel groups comprising a total of 142 newly registered patients for primary liver transplantation has been designed to assess the safety and efficacy of the long-term administration of ORAL IMPACT®, an immunonutrient formula, while waiting for a graft. Patients will be enrolled the day of registration on the waiting list for liver transplantation. Study ends on the day of transplantation. Primary endpoints include patients' nutritional and physiological status, as measured by mid-arm muscle area, triceps skin fold thickness, grip strength, and fatigue score, as well as patients' health related quality of life. Furthermore, patients will be followed for 12 postoperative weeks to evaluate anabolic recovery after transplantation as shown by reduced post-transplant mechanical ventilation, hospital stay, wound healing, infectious morbidities (pneumonia, intra-abdominal abscess, sepsis, line sepsis, wound infection, and urinary tract infection), acute and chronic rejection, and mortality. Discussion. Formulas enriched with arginine, ω-3 fatty acids, and nucleotides have been proven to be beneficial in reducing postoperative infectious complications and length of hospital stay among the patients undergoing elective gastrointestinal surgery. Possible mechanisms include downregulation of the inflammatory responses to surgery and immune modulation rather than a sole nutritional effect.

Official Title
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Randomized Controlled Double Blind Multi-Center Clinical Trial to Assess the Effects of Preoperative Long-Term Immunonutrition in Patients Listed for Liver Transplantation

Conditions
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Newly Registered Patients for Primary Liver Transplantation

Intervention / Treatment
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* Dietary Supplement: Immunonutrition
* Dietary Supplement: food for special medical purposes (FSMP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between 18 and 68 years of age Scheduled for first liver transplantation Written informed consent Protein-calorie malnutrition: Mid-arm muscle area (MAMA) <85% standard Exclusion Criteria: Patients < 18 and > 68 years Pregnant or nursing women History of hypersensitivity to arginine, ω-3 fatty acids, or nucleotides Inability to take oral nutrition Patients with fulminant or subacute hepatic failure requiring urgent transplantation Mental condition rendering the subject incapable to understand the nature, scope, and consequences of the trial Simultaneous participation in another clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 68 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Study group will receive formula enriched with arginine, ω-3 fatty acids, and nucleotides once daily | Dietary Supplement: Immunonutrition<br>* food for special medical purpose (FSMP)<br>* Other names: ORAL IMPACT®;|
| Active Comparator: 2<br>controls receive an isocaloric isonitrogenous non-specific nutritional support | Dietary Supplement: food for special medical purposes (FSMP)<br>* an isocaloric isonitrogenous non-specific nutritional support<br>* Other names: IMPACT-Control Supplement;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improved patients' nutritional and physiological status, fatigue score, as well as patients' health related quality of life. |  | while in the waiting list for liver transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| enhanced anabolic recovery after transplantation as shown by reduced post-transplant morbidities and mortalities |  | the first 12 posttransplant weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunonutrition, immune enhancing diets, arginine, ω-3 fatty acids, nucleotides, liver transplantation, clinical trial