High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial

Abstract

IntroductionAcute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high quality experimental observations in this area, no randomised trials have been conducted to date to address the requirements for energy intake in the early phase of AP.Methods/designThis is a randomised controlled two-arm double-blind multicentre trial. Patients with AP will be randomly assigned to groups A (30 kcal/kg/day energy administration starting within 24 hours of hospital admission) or B (low energy administration during the first 72 hours of hospital admission). Energy will be delivered by nasoenteric tube feeding with additional intravenous glucose supplementation or total parenteral nutrition if necessary. A combination of multiorgan failure for more than 48 hours and mortality is defined as the primary endpoint, whereas several secondary endpoints such as length of hospitalisation or pain will be determined to elucidate more detailed differences between the groups. The general feasibility, safety and quality checks required for high quality evidence will be adhered to.Ethics and disseminationThe study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (55961-2/2016/EKU). This study will provide evidence as to whether early high energy nutritional support is beneficial in the clinical management of AP. The results of this trial will be published in an open access way and disseminated among medical doctors.Trial registrationThe trial has been registered at the ISRCTN (ISRTCN 63827758).

Haemorheological and haemostatic alterations in coeliac disease and inflammatory bowel disease in comparison with non-coeliac, non-IBD subjects (HERMES): a case–control study protocol

“…The Centre for Translational Medicine at the University of Pécs, which was established to advance medical research in gastroenterology, is the co-ordinator and designer of the HERMES study. The centre is experienced in running investigator-initiated clinical trials 46. A steering committee will be set up to supervise the entire study process.…”

Acute Pancreatitis: Exploring Nutrition Implications

“…3 Early phases of AP cause mitochondrial damage and adenosine triphosphate depletion in pancreatic ductal cells driving the cell death, ultimately leading to pancreatic necrosis. 5,7 Alcohol, however, exerts localized toxic effects on pancreatic stellate cells. This causes inflammation of the pancreas during AP.…”

“…1 Overall mortality for all causes of AP is ≈2%. 2,[5][6][7][8][9] Age >60, multiple comorbid conditions, obesity, and long-term heavy alcohol use all predict higher mortality. 2 Admission laboratory results are also associated with a higher likelihood of mortality (eg, hemoconcentration, azotemia, C-reactive protein (CRP) >150, and acute fluctuations of blood glucose).…”

“…22 If bacterial translocation can be reduced through maintenance of intraluminal nutrition therapy, it is reasonable to attempt it. 7 EN preserves gut barrier integrity and function, reducing colonic bacterial overgrowth and diminishing endotoxin and bacterial translocation. 7,38,39 EN over PN showed decreased levels of TNF, IL-1, IL-6, and IL-8 in the EN group.…”

“…7 EN preserves gut barrier integrity and function, reducing colonic bacterial overgrowth and diminishing endotoxin and bacterial translocation. 7,38,39 EN over PN showed decreased levels of TNF, IL-1, IL-6, and IL-8 in the EN group. 38 The 2016 American Society for Parenteral and Enteral Nutrition/society of critical care medicine guidelines recommend EN over PN and show a reduction in infectious morbidity (42.6% vs 16.1%, P < .0001) and mortality (16.4% vs 6.1%, P = .02).…”