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

Sponsor

Heidelberg University (Other)

Overall Status

Unknown status

CT.gov ID

NCT00495859

Collaborator

Novartis (Industry)

156

Enrollment

Location

Arms

Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Newly Registered Patients for Primary Liver Transplantation	Dietary Supplement: Immunonutrition Dietary Supplement: food for special medical purposes (FSMP)	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

156 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Supportive Care

Official Title:

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

Study Start Date :

Apr 1, 2008

Anticipated Primary Completion Date :

Apr 1, 2011

Anticipated Study Completion Date :

Apr 1, 2011

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: 1

Study group will receive formula enriched with arginine, ω-3 fatty acids, and nucleotides once daily

Dietary Supplement: Immunonutrition

food for special medical purpose (FSMP)

Other Names:

ORAL IMPACT®

Active Comparator: 2

controls receive an isocaloric isonitrogenous non-specific nutritional support

Dietary Supplement: food for special medical purposes (FSMP)

an isocaloric isonitrogenous non-specific nutritional support

Other Names:

IMPACT-Control Supplement

Outcome Measures

Primary Outcome Measures

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

enhanced anabolic recovery after transplantation as shown by reduced post-transplant morbidities and mortalities [the first 12 posttransplant weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 68 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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