Clinical trial NCT00495859: Effects of Preoperative Long-Term Immunonutrition in Patients Listed for Liver Transplantation
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Newly Registered Patients for Primary Liver Transplantation
Keywords: Immunonutrition
immune enhancing diets
arginine
ω-3 fatty acids
nucleotides
liver transplantation
clinical trial
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2007-07-03
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: improved patients' nutritional and physiological status, fatigue score, as well as patients' health related quality of life.
timeFrame: while in the waiting list for liver transplantation
Secondary outcomes:
measure: enhanced anabolic recovery after transplantation as shown by reduced post-transplant morbidities and mortalities
timeFrame: the first 12 posttransplant weeks
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Department of Surgery, Ruprecht-Karls University
state: Baden-Württemberg
Study officials:
affiliation: Department of Surgery, Ruprecht-Karls University of Heidelberg, Germany
name: Peter Schemmer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nickkholgh A, Schneider H, Encke J, Buchler MW, Schmidt J, Schemmer P. PROUD: effects of preoperative long-term immunonutrition in patients listed for liver transplantation. Trials. 2007 Aug 27;8:20. doi: 10.1186/1745-6215-8-20.