Clinical trial NCT04862234: Perioperative Stress Hyperglycemia in General and Vascular Surgery Patients
Official title: Perioperative Stress Hyperglycemia in General and Vascular Surgery Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hyperglycemia Stress
Keywords: Perioperative
Surgery
Stress Hyperglycemia
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2021-04-27
Enrollment: 16
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Hyperglycemia is seen in approximately 30% of patients who do not have a history of diabetes and undergo general surgery. Hyperglycemia in this setting is associated with increased risk of postoperative complications. The purpose of this study is to investigate risk factors for developing high sugars during the time of surgery, and if these high sugars can be prevented by the use of an injectable diabetes medication (dulaglutide) prior to surgery.

Detailed description: Stress hyperglycemia (SH), defined as a blood glucose \>140 mg/dl in hospitalized patients without a prior history of diabetes mellitus (DM) is associated with increased risk of complications and mortality compared to patients with normoglycemia and with known history of DM. Increased counterregulatory hormones (cortisol, glucagon, epinephrine, growth hormone), free fatty acids, inflammation and oxidative stress are likely involved in the pathogenesis of impaired insulin secretion and action leading to stress hyperglycemia. However, no prospective studies have comprehensively examined preoperative glycemic control profiles and their association with the incidence, clinical predictors and underlying mechanisms of SH in general surgical patients. Accordingly, the researchers propose a prospective study investigating clinical, metabolic and inflammatory/oxidative stress biomarker profiles leading to SH. This study will use continuous glucose monitoring (CGM) technology to fully characterize the onset, duration and severity of SH during the perioperative period.

Given the association between stress hyperglycemia and poor hospital outcomes, this study aims to determine if the prevention of stress hyperglycemia is feasible with the single administration of a weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA), a common medication used to treat patients with established diabetes. In addition, the researchers will explore the role of beta-cell function, insulin resistance, and inflammation on the pathogenesis of stress hyperglycemia.

The goals of this study are to: 1) conduct an extensive analysis of preoperative glycemic control and its relationship to clinical, metabolic and biomarker profiles of SH in a high-risk population, and 2) conduct a pilot randomized controlled trial to prospectively determine if single dose use of dulaglutide can improve perioperative glycemic control compared to insulin administration (standard-of-care). Patients qualifying for the study will be approached at their preoperative clinic visit and invited to participate in the prospective observational study arm (Aim 1), and in the interventional trial for prevention of SH with dulaglutide (Aim 2) if they meet inclusion criteria based on oral glucose tolerance testing (OGTT) or lab testing performed for Aim 1. Within 72 hours prior to planned surgery, consented patients will present to the clinical research center (CRC) to undergo evaluation with OGTT and lab testing with CGM placement. Those patients with OGTT or lab results consistent with a diagnosis of prediabetes or newly diagnosed diabetes will be asked if they would like to participate in Aim 2. Patients consenting to participate in Aim 2 will be randomized to receive a subcutaneous injection of dulaglutide 0.75 mg or placebo during the CRC visit, and glycemic control parameters will be followed postoperatively during surgical admission (up to 14 days). In addition to the above, baseline and postoperative levels of serum inflammatory and oxidative stress markers will be obtained to provide further information regarding beta-cell function and insulin resistance in relation to the development of stress hyperglycemia.

Eligibility criteria: Inclusion criteria:

* Men and women without known history of diabetes with ages between 45 and 80 years undergoing non-cardiac general or vascular surgery
* BMI ≥30 kg/m2 and pre-DM or DM by OGTT or HbA1c

Exclusion criteria:

* Patients prescribed or taking antihyperglycemic medications
* Patients undergoing cardiac surgery or patients anticipated to require ICU care
* Patients expected to be admitted less than 48-72 hours after surgery
* Severely impaired renal function (eGFR \< 30 mL/min) or clinically significant hepatic failure
* Treatment with oral (equivalent to prednisone \> 5 mg/day) or injectable corticosteroids
* Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study; unable to consent
* Pregnant or breast feeding at time of enrollment
* Prisoners
* Patients undergoing gastrointestinal surgery or at high risk for gastrointestinal obstruction/ileus or expected to require gastrointestinal suction
* Patients with delayed gastric emptying, pancreatic or gallbladder disease
* Patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2)

Primary outcomes:
measure: Percentage of Time in Target Glucose Range (70-140 mg/dL) by CGM
timeFrame: During hospitalization (up to 5 days postoperatively)
Secondary outcomes:
measure: Percentage of Time in Hyperglycemia (Glucose>140 mg/dL)
timeFrame: During hospitalization (up to 5 days postoperatively)
measure: Percentage of Time in Hyperglycemia (Glucose>180 mg/dL)
timeFrame: During hospitalization (up to 5 days postoperatively)
measure: Percentage of Time in Hypoglycemia (Glucose <70 mg/dL)
timeFrame: During hospitalization (up to 5 days postoperatively)
measure: Percentage of Time in Hypoglycemia (Glucose <54 mg/dL)
timeFrame: During hospitalization (up to 5 days postoperatively)
measure: Percentage of Time in Hypoglycemia (Glucose <40 mg/dL)
timeFrame: During hospitalization (up to 5 days postoperatively)
measure: Mean Onset of Stress Hyperglycemia During the Postoperative Period
timeFrame: During hospitalization (up to 5 days postoperatively)
measure: Mean Duration of Stress Hyperglycemia During the Postoperative Period
timeFrame: During hospitalization (up to 5 days postoperatively)
measure: Mean Daily Glucose Values
timeFrame: During hospitalization (up to 5 days postoperatively)
measure: Maximum Daily Glucose Values
timeFrame: During hospitalization (up to 5 days postoperatively)
measure: Perioperative Insulin Requirements
timeFrame: During hospitalization (up to 5 days postoperatively)
measure: Change in Plasma Cortisol Level
timeFrame: Baseline, 48 to 72 hours postoperatively
measure: Change in Level of Free Fatty Acids (FFA)
timeFrame: Baseline, 48 to 72 hours postoperatively
measure: Change in High Sensitivity C-reactive Protein (hsCRP) Level
timeFrame: Baseline, 48 to 72 hours postoperatively
measure: Change in Tumor Necrosis Factor-alpha (TNF-α) Level
timeFrame: Baseline, 48 to 72 hours postoperatively
measure: Change in Adiponectin Level
timeFrame: Baseline, 48 to 72 hours postoperatively
measure: Change in Level of Thiobarbituric Acid Reactive Substances (TBARS)
timeFrame: Baseline, 48 to 72 hours postoperatively
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Grady Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Georgia Davis, MD
role: PRINCIPAL_INVESTIGATOR
References: