Sepsis
Conditions
Keywords
enteral nutrition, inflammation, incretin hormones, microbiome
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.
Interventions
OTHEREnteral Dextrose Infusion
A standard solution of 50% Dextrose (0.85 kcal/mL) will be infused via enteral route at a rate of 10 mL per hour for a duration of 24 hours.
OTHERFree Water Infusion
An infusion of free water will be initiated via enteral route at a rate of 10 mL per hour for a duration of 24 hours.
Sponsors
National Institutes of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Infusion solutions will be prepared by pharmacy services at the local institution but participants, investigators, care providers, and outcomes assessors will be blinded to group allocation until the end of the study.
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)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma IL-6 | 24 hours after start of infusion | Pro-inflammatory cytokine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Additional pro-inflammatory cytokines | 24 hours after start of infusion | Circulating levels of other pro-inflammatory cytokines including IL-1 beta and TNF-alpha (each to be determined in pg/mL) |
| Incretin hormone levels | 24 hours after start of infusion | Circulating levels of the intestine-derived hormones GIP and GLP-1 (each to be determined in pg/mL) |
| Microbiome composition | 24 hours after start of infusion | Analysis of the composition and distribution of microorganisms of the gut and respiratory microbiome measured after intervention from tracheal aspirates and rectal swabs |
| Glycemic control | First 24 hours | Capillary blood glucose measurements during infusion period |
| Mortality | 30 days | In-hospital mortality at 30 days |
Countries
United States
Outcome results
None listed