Clinical trial NCT03454087: Study of Early Enteral Dextrose in Sepsis
Official title: Study of Early Enteral Dextrose in Sepsis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Keywords: enteral nutrition
inflammation
incretin hormones
microbiome
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of General Medical Sciences (NIGMS)
First posted: 2018-03-05
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized in a blinded 1:1 fashion to receive either a low level enteral infusion of dextrose solution (intervention group) or an enteral infusion of free water (placebo group)
Primary purpose: TREATMENT

Brief summary: This study is a prospective single-center randomized double-blinded placebo-controlled clinical trial testing the effects of early enteral dextrose as a therapeutic agent in critically ill patients with sepsis. Primary outcomes are differences in circulating plasma levels of the pro-inflammatory cytokine IL-6 to be tested 24 hours after the start of enteral infusion. Secondary outcomes include differences in circulating incretin hormone levels, differences in other pro-inflammatory cytokines including IL-1β and TNF-α, changes in intestinal microbial composition and function after intervention, glycemic control and variability as assessed by capillary blood glucose measurements and exogenous insulin dosing during the intervention period, and clinical outcomes including intensive care unit (ICU) and hospital stay and in-hospital mortality.

Detailed description: The central objective of this research project is to determine how early caloric support impacts inflammatory and metabolic outcomes in the acute phase of sepsis. Preliminary data from our mouse models suggest that provision of dextrose via an intravenous route, even at low levels early in the course of sepsis, markedly impairs glucose tolerance and decreases insulin sensitivity and insulin secretion. In contrast, provision of low-level dextrose by the enteral route at identical levels during the early phase of sepsis is associated with decreased inflammation, increased secretion of beneficial intestine-derived incretin hormones, and significant improvements in glucose metabolism. The goals of this clinical study are to translate findings on the beneficial role of early enteral dextrose in a pilot interventional trial in critically-ill patients with sepsis. This clinical trial will provide further insight into the optimal timing and route of early caloric support in the care of septic patients-an area of clinical practice that will benefit from further studies in fundamental biology and clear guidelines for physicians.

Eligibility criteria: Inclusion Criteria:

1. New presentation of sepsis characterized by a confirmed or suspected infection, with an acute increase from baseline in a modified Sepsis-Related Organ Failure Assessment (SOFA) score of greater than or equal to 2 points. If baseline values are unknown, baseline SOFA score of 0 will be assumed.
2. Available enteral access defined by: (1) an existing nasogastric or orogastric tube, (2) plans to place a nasogastric or orogastric tube, or (3) an existing percutaneous endoscopic gastrostomy (PEG) tube.
3. Less than 48 hours since meeting criteria for sepsis.
4. Expected to stay at least 24 hours in the ICU.

Exclusion Criteria:

1. Pre-existing continuous enteral tube feed use prior to study entry.
2. Diabetic ketoacidosis or diabetic hyperosmolar hyperglycemic syndrome.
3. Previously enrolled in this study within the same hospital admission.
4. ICU physician request to exclude patient based on clinical assessment.

Primary outcomes:
measure: Plasma IL-6
timeFrame: 24 hours after start of infusion
Secondary outcomes:
measure: Additional pro-inflammatory cytokines
timeFrame: 24 hours after start of infusion
measure: Incretin hormone levels
timeFrame: 24 hours after start of infusion
measure: Microbiome composition
timeFrame: 24 hours after start of infusion
measure: Glycemic control
timeFrame: First 24 hours
measure: Mortality
timeFrame: 30 days
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Faraaz A Shah, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shah FA, Kitsios GD, Yende S, Dunlap DG, Scholl D, Chuan B, Al-Yousif N, Zhang Y, Nouraie SM, Morris A, Huang DT, O'Donnell CP, McVerry BJ. A Pilot Double-Blind Placebo-Controlled Randomized Clinical Trial to Investigate the Effects of Early Enteral Nutrients in Sepsis. Crit Care Explor. 2021 Oct 8;3(10):e550. doi: 10.1097/CCE.0000000000000550. eCollection 2021 Oct.
citation: Shah FA, Mahmud H, Gallego-Martin T, Jurczak MJ, O'Donnell CP, McVerry BJ. Therapeutic Effects of Endogenous Incretin Hormones and Exogenous Incretin-Based Medications in Sepsis. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5274-5284. doi: 10.1210/jc.2019-00296.