Study of Early Enteral Dextrose in Sepsis (SEEDS)

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.

Study Overview

• Status: Completed
• Conditions: Sepsis
• Intervention / Treatment: Other: Enteral Dextrose Infusion; Other: Free Water Infusion

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15237
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Enteral Dextrose Infusion; Critically-ill participants with sepsis enrolled in the interventional arm will receive a 24-hour infusion of dextrose solution by the enteral route to be initiated via an existing nasogastric or orogastric tube within the first 48 hours of meeting sepsis criteria.	Other: Enteral 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.
PLACEBO_COMPARATOR: Placebo; Critically-ill participants with sepsis in the placebo arm will receive a 24-hour enteral free water infusion via an existing orogastric or nasogastric tube within 48 hours of meeting sepsis criteria.	Other: Free 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma IL-6	Pro-inflammatory cytokine	24 hours after start of infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional pro-inflammatory cytokines	Circulating levels of other pro-inflammatory cytokines including IL-1 beta and TNF-alpha (each to be determined in pg/mL)	24 hours after start of infusion
Incretin hormone levels	Circulating levels of the intestine-derived hormones GIP and GLP-1 (each to be determined in pg/mL)	24 hours after start of infusion
Microbiome composition	Analysis of the composition and distribution of microorganisms of the gut and respiratory microbiome measured after intervention from tracheal aspirates and rectal swabs	24 hours after start of infusion
Glycemic control	Capillary blood glucose measurements during infusion period	First 24 hours
Mortality	In-hospital mortality at 30 days	30 days

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Faraaz A Shah, MD, University of Pittsburgh

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 4, 2018
• Primary Completion (ACTUAL): March 2, 2020
• Study Completion (ACTUAL): April 1, 2020

Study Registration Dates

• First Submitted: February 19, 2018
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (ACTUAL): March 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 7, 2020
• Last Update Submitted That Met QC Criteria: April 3, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: inflammation; microbiome; enteral nutrition; incretin hormones
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: PRO17010532; 5K23GM122069 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No