Perioperative Stress Hyperglycemia in General and Vascular Surgery Patients

Hyperglycemia Stress Clinical Trial

Official title:

Perioperative Stress Hyperglycemia in General and Vascular Surgery Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04862234
• Other study ID #: IRB00097659
• Secondary ID: K23DK122199
• Status: Recruiting
• Phase: Phase 4
• Start date: July 29, 2021
• Est. completion date: May 30, 2026

Study information

• Verified date: April 2023
• Source: Emory University
• Contact: Georgia Davis, MD
• Phone: 404-251-8957
• Email: georgia.marie.davis[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 245
• Est. completion date: May 30, 2026
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

Inclusion criteria (Aim 1):

• Men and women between the ages of 45 and 80 years undergoing non-cardiac general or vascular surgery

• BMI =30 kg/m^2 without a previously known history of DM

Inclusion criteria (Aim 2):

• Men and women without known history of diabetes with ages between 45 and 80 years undergoing non-cardiac general or vascular surgery participating in Aim 1.

• BMI =30 kg/m2 and pre-DM or DM by OGTT or HbA1c.

Exclusion criteria (Aim 1):

• 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

Exclusion criteria (Aim 2):

• Same as in Aim 1, with the following additional exclusion criteria:

• 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)

Related Conditions & MeSH terms

• Hyperglycemia
• Hyperglycemia Stress

Intervention

Drug:
• Dulaglutide
A subcutaneous injection of dulaglutide 0.75 mg will be administered within 72 hours prior to a planned surgical intervention.
• Placebo
A subcutaneous injection of a saline placebo will be administered within 72 hours prior to a planned surgical intervention.

Device:
• Continuous glucose monitor (CGM), blinded
Continuous glucose monitor (CGM) sensor will be placed preoperatively and continued during surgical hospitalization to monitor glucose levels. CGM provides an estimated capillary blood glucose (BG) level through direct measurement of interstitial glucose levels every 5-15 minutes.

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	Grady Hospital	Atlanta	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Emory University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of stress hyperglycemia (SH)	Incidence of stress hyperglycemia will be determine in a population at high-risk for perioperative dysglycemia among participants in Aim 1.	Up to 14 days (depending on length of hospitalization)
Primary	Percentage of time in target glucose range (70-140 mg/dL) by CGM	Proportion of time in target glucose range (70-140 mg/dL) by CGM data will be calculated for participants of Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Baseline Insulin Secretion	Baseline insulin secretion between patients with and without stress hyperglycemia will be examined among participants in Aim 1.	Baseline
Secondary	Baseline Insulin Sensitivity	Baseline insulin sensitivity between patients with and without stress hyperglycemia will be examined among participants in Aim 1.	Baseline
Secondary	Mean Onset of Stress Hyperglycemia (Glucose >140 mg/dL)	Mean onset time of stress hyperglycemia by CGM (glucose >140 mg/dL) during the postoperative period will be examined for participants of Aim 1.	Up to 14 days (depending on length of hospitalization)
Secondary	Mean Duration of Stress Hyperglycemia (Glucose >140 mg/dL)	The mean duration of stress hyperglycemia by CGM (glucose >140 mg/dL) during the postoperative period will be examined for participants of Aim 1.	Up to 14 days (depending on length of hospitalization)
Secondary	Mean Daily Glucose Values	The mean daily glucose values values, as measured by both point-of-care (POC) glucose testing and CGM data, will be examined among participants in Aim 1.	Up to 14 days (depending on length of hospitalization)
Secondary	Maximum Daily Glucose Values	The maximum daily glucose values values, as measured by both POC glucose testing and CGM data, will be examined among participants in Aim 1.	Up to 14 days (depending on length of hospitalization)
Secondary	Total Daily Insulin Dose	The total daily insulin dose in patients with and without stress hyperglycemia will be examined among participants in Aim 1.	Up to 14 days (depending on length of hospitalization)
Secondary	Length of Hospital Stay	The length of hospital stay (in days) in patients with and without stress hyperglycemia will be examined among participants in Aim 1.	Up to 14 days (depending on length of hospitalization)
Secondary	Number of ICU Transfers	The number of ICU transfers in patients with and without stress hyperglycemia will be examined among participants in Aim 1.	Up to 14 days (depending on length of hospitalization)
Secondary	Number of Hospital Readmissions After Discharge	Number of hospital readmissions after discharge patients with and without stress hyperglycemia (SH) will be examined among participants in Aim 1.	Up to 3 months after discharge
Secondary	Number of Emergency Room Visits After Discharge	The number of emergency room visits after discharge patients with and without stress hyperglycemia (SH) will be examined among participants in Aim 1.	Up to 3 months after discharge
Secondary	Number of Participants Experiencing Complications	A composite of complications including wound infection, respiratory failure, pneumonia, acute kidney injury (increase in creatinine by 0.5 mg/dL), and major adverse cardiac events (MACE) will be examined among participants in Aim 1.	Up to 14 days (depending on length of hospitalization)
Secondary	Percentage of Time in Hyperglycemia (Glucose>140 mg/dL)	The percentage of time in hyperglycemia with glucose>140 mg/dL will be examined for participants of Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Percentage of Time in Hyperglycemia (Glucose>180 mg/dL)	The percentage of time in hyperglycemia with glucose>180 mg/dL will be examined for participants of Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Percentage of Time in Hypoglycemia (Glucose <70 mg/dL)	The percentage of time in hypoglycemia with glucose <70 mg/dL will be examined for participants of Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Percentage of Time in Hypoglycemia (Glucose <54 mg/dL)	The percentage of time in hypoglycemia with glucose <54 mg/dL will be examined for participants of Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Percentage of Time in Hypoglycemia (Glucose <40 mg/dL)	The percentage of time in hypoglycemia with glucose <40 mg/dL will be examined for participants of Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Mean Onset of Stress Hyperglycemia During the Postoperative Period	The mean onset time of stress hyperglycemia during the postoperative period by CGM data will be examined for participants of Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Mean Duration of Stress Hyperglycemia During the Postoperative Period	The mean duration of stress hyperglycemia during the postoperative period by CGM data will be examined for participants of Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Mean Daily Glucose Values (Aim 2)	The mean daily glucose values values, as measured by both POC glucose testing and CGM data, will be examined among participants in Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Maximum Daily Glucose Values (Aim 2)	The maximum daily glucose values values, as measured by both POC glucose testing and CGM data, will be examined among participants in Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Perioperative Insulin Requirements	Perioperative insulin requirements will be assessed as the total daily insulin dose, among participants from Aim 2.	Up to 14 days (depending on length of hospitalization)
Secondary	Change in Plasma Cortisol Level	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.	Baseline, 48 to 72 hours postoperatively
Secondary	Change in Level of Free Fatty Acids (FFA)	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.	Baseline, 48 to 72 hours postoperatively
Secondary	Change in High Sensitivity C-reactive Protein (hsCRP) Level	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.	Baseline, 48 to 72 hours postoperatively
Secondary	Change in Tumor Necrosis Factor-alpha (TNF-a) Level	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.	Baseline, 48 to 72 hours postoperatively
Secondary	Change in Adiponectin Level	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.	Baseline, 48 to 72 hours postoperatively
Secondary	Change in Level of Thiobarbituric Acid Reactive Substances (TBARS)	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.	Baseline, 48 to 72 hours postoperatively