Dataset Information

Rationale for and Design of the Study of Early Enteral Dextrose in Sepsis: A Pilot Placebo-Controlled Randomized Clinical Trial.

ABSTRACT:

Background

Sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection and affects over 1 million Americans annually. Loss of glycemic control in sepsis is associated with increased morbidity and mortality, and novel approaches are needed to promote euglycemia and improve outcomes in sepsis. Recent studies from our laboratory demonstrate that early low-level enteral dextrose infusion in septic mice attenuates the systemic inflammatory response and improves glycemic control by inducing intestine-derived incretin hormone secretion.

Aim

The aim of the Study of Early Enteral Dextrose in Sepsis (SEEDS) is to test the effect of a 24-hour enteral dextrose infusion in critically ill septic patients as a therapeutic agent to decrease systemic inflammation and promote euglycemia.

Methods

SEEDS is a single-center, double-blind, randomized, controlled trial that will enroll 60 septic patients admitted to the intensive care units at the University of Pittsburgh Medical Center Health System in Pittsburgh. Participants will be randomized 1:1 to receive enteral dextrose (n = 30) or water (placebo, n = 30) infusion for 24 hours. The primary outcome is the circulating interleukin-6 level measured after the 24-hour infusion compared between dextrose and placebo groups. Secondary outcomes include postinfusion circulating insulin, incretin, and other proinflammatory cytokine levels, as well as incidence of hyperglycemia and hypoglycemia during the infusion period.

Discussion

This trial will characterize the effects of early enteral dextrose on endogenous endocrine pathways and the systemic inflammatory response in sepsis. The results of this trial will inform future larger interventional studies of early enteral nutrients in critically ill patients with sepsis.

SUBMITTER: Shah FA

PROVIDER: S-EPMC6884652 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Rationale for and Design of the Study of Early Enteral Dextrose in Sepsis: A Pilot Placebo-Controlled Randomized Clinical Trial.

Shah Faraaz Ali FA Kitsios Georgios D GD Zhang Yingze Y Morris Alison A Yende Sachin S Huang David T DT O'Donnell Christopher P CP McVerry Bryan J BJ

JPEN. Journal of parenteral and enteral nutrition 20190530 3

<h4>Background</h4>Sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection and affects over 1 million Americans annually. Loss of glycemic control in sepsis is associated with increased morbidity and mortality, and novel approaches are needed to promote euglycemia and improve outcomes in sepsis. Recent studies from our laboratory demonstrate that early low-level enteral dextrose infusion in septic mice attenuates the systemic inflammatory ...[more]

PMID: 31148210

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Project description:Preclinical studies from our laboratory demonstrated therapeutic effects of enteral dextrose administration in the acute phase of sepsis, mediated by the intestine-derived incretin hormone glucose-dependent insulinotropic peptide. The current study investigated the effects of an early enteral dextrose infusion on systemic inflammation and glucose metabolism in critically ill septic patients.DesignSingle-center, double-blind, placebo-controlled randomized pilot clinical trial (NCT03454087).SettingTertiary-care medical center in Pittsburgh, PA.PatientsCritically ill adult patients within 48 hours of sepsis diagnosis and with established enteral access.InterventionsParticipants were randomized 1:1 to receive a continuous water (placebo) or enteral dextrose infusion (50% dextrose; 0.5 g/mL) at 10 mL per hour for 24 hours.Measurements and main resultsWe randomized 58 participants between June 2018 and January 2020 (placebo: n = 29, dextrose: n = 29). Protocol adherence was high with similar duration of study infusion in the placebo (median duration, 24 hr [interquartile range, 20.9-24 hr]) and dextrose (23.9 hr [23-24 hr]) groups (p = 0.59). The primary outcome of circulating interleukin-6 at end-infusion did not differ between the dextrose (median, 32 pg/mL [19-79 pg/mL]) and placebo groups (24 pg/mL [9-59 pg/mL]; p = 0.13) with similar results in other measures of the systemic host immune response. Enteral dextrose increased circulating glucose-dependent insulinotropic peptide (76% increase; 95% CI [35-119]; p < 0.01) and insulin (53% [17-88]; p < 0.01) compared with placebo consistent with preclinical studies, but also increased blood glucose during the 24-hour infusion period (153 mg/dL [119-223] vs 116 mg/dL [91-140]; p < 0.01). Occurrence of emesis, ICU and hospital length of stay, and 30-day mortality did not differ between the placebo and enteral dextrose groups.ConclusionsEarly infusion of low-level enteral dextrose in critically ill septic patients increased circulating levels of insulin and the incretin hormone glucose-dependent insulinotropic peptide without decreasing systemic inflammation.

Project description:IntroductionFrontotemporal dementia (FTD) is a neurodegenerative disorder for which there is no effective pharmacological treatment. Recently, interneuron activity responsible for fast oscillatory brain activity has been found to be impaired in a mouse model of FTD with consequent cognitive and behavioral alterations. In this study, we aim to investigate the safety, tolerability, and efficacy of a novel promising therapeutic intervention for FTD based on 40 Hz transcranial alternating current stimulation (tACS), a form of non-invasive brain stimulation thought to engage neural activity in a frequency-specific manner and thus suited to restore altered brain oscillatory patterns.MethodsThis is a multi-site, randomized, double-blind, placebo-controlled trial on 50 patients with a diagnosis of behavioral variant FTD (bvFTD). Participants will be randomized to undergo either 30 days of 1-hour daily tACS or Sham (placebo) tACS. The outcomes will be assessed at baseline, right after the intervention and at a 3- to 6-months follow-up. The primary outcome measures are represented by the safety and feasibility of tACS administration, which will be assessed considering the nature, frequency, and severity of adverse events as well as attrition rate, respectively. To assess secondary outcomes, participants will undergo extensive neuropsychological and behavioral assessments and fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans to evaluate changes in brain metabolism, functional and structural magnetic resonance imaging (MRI), resting and evoked electroencephalography, as well as blood biomarkers to measure changes in neurodegenerative and neuroinflammatory markers.ResultsThe trial started in October 2020 and will end in October 2023. Study protocols have been approved by the local institutional review board (IRB) at each data-collection site.DiscussionThis study will evaluate the safety and tolerability of 40 Hz tACS in bvFTD patients and its efficacy on gamma oscillatory activity, cognitive function, and brain glucose hypometabolism.

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Dataset Information

Rationale for and Design of the Study of Early Enteral Dextrose in Sepsis: A Pilot Placebo-Controlled Randomized Clinical Trial.

Background

Aim

Methods

Discussion

Publications

Rationale for and Design of the Study of Early Enteral Dextrose in Sepsis: A Pilot Placebo-Controlled Randomized Clinical Trial.

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