Hyperglycemia StressPhase 4NCT04862234
Perioperative Stress Hyperglycemia in General and Vascular Surgery Patients
A Phase 4 study testing Dulaglutide and Continuous glucose monitor (CGM), blinded in people with Hyperglycemia Stress, run by Emory University at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 45 to 80 years
- Conditions the study is for
- Hyperglycemia Stress
- What is being tested?
- Dulaglutide and Continuous glucose monitor (CGM), blinded
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Aug 2021to 22 Jun 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Emory University Hospital
Atlanta, Georgia, 30322
Grady Hospital
Atlanta, Georgia, 30322
About this study
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.
Read the 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.
- Conditions
- Hyperglycemia Stress
- Being tested
- Dulaglutide, Placebo, Continuous glucose monitor (CGM), blinded
- Keywords
- Perioperative, Surgery, Stress Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DulaglutideDrug
Also called Trulicity
A subcutaneous injection of dulaglutide 0.75 mg will be administered within 72 hours prior to a planned surgical intervention.
PlaceboDrug
A subcutaneous injection of a saline placebo will be administered within 72 hours prior to a planned surgical intervention.
Continuous glucose monitor (CGM), blindedDevice
Also called FreeStyle Libre Pro
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.
| Study group | Role | What they receive |
|---|---|---|
| Dulaglutide | Experimental | Participants randomized to receive dulaglutide within 72 hours prior to a planned surgery. Receives: Drug: Dulaglutide; Device: Continuous glucose monitor (CGM), blinded |
| Placebo | Placebo comparator | Participants randomized to receive a placebo to match dulaglutide within 72 hours prior to a planned surgery. Receives: Drug: Placebo; Device: Continuous glucose monitor (CGM), blinded |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Time in Target Glucose Range (70-140 mg/dL) by CGM
The percentage of time in the target glucose range of 70-140 mg/dL, as measured by a continuous glucose monitor (CGM) data was determined.
Measured: During hospitalization (up to 5 days postoperatively)
Secondary outcomes (16)
Percentage of Time in Hyperglycemia (Glucose>140 mg/dL)
The percentage of time in hyperglycemia with glucose>140 mg/dL will be examined.
Measured: During hospitalization (up to 5 days postoperatively)
Percentage of Time in Hyperglycemia (Glucose>180 mg/dL)
The percentage of time in hyperglycemia with glucose>180 mg/dL will be examined.
Measured: During hospitalization (up to 5 days postoperatively)
Percentage of Time in Hypoglycemia (Glucose <70 mg/dL)
The percentage of time in hypoglycemia with glucose <70 mg/dL will be examined.
Measured: During hospitalization (up to 5 days postoperatively)
Percentage of Time in Hypoglycemia (Glucose <54 mg/dL)
The percentage of time in hypoglycemia with glucose <54 mg/dL will be examined.
Measured: During hospitalization (up to 5 days postoperatively)
Percentage of Time in Hypoglycemia (Glucose <40 mg/dL)
The percentage of time in hypoglycemia with glucose <40 mg/dL will be examined.
Measured: During hospitalization (up to 5 days postoperatively)
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.
Measured: During hospitalization (up to 5 days postoperatively)
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.
Measured: During hospitalization (up to 5 days postoperatively)
Mean Daily Glucose Values
The mean daily glucose values, as measured by both point of care (POC) glucose testing and CGM data, will be examined.
Measured: During hospitalization (up to 5 days postoperatively)
Maximum Daily Glucose Values
The maximum daily glucose values, as measured by both POC glucose testing and CGM data, will be examined.
Measured: During hospitalization (up to 5 days postoperatively)
Perioperative Insulin Requirements
Perioperative insulin requirements will be assessed as the total daily insulin dose.
Measured: During hospitalization (up to 5 days postoperatively)
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.
Measured: Baseline, 48 to 72 hours postoperatively
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.
Measured: Baseline, 48 to 72 hours postoperatively
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.
Measured: Baseline, 48 to 72 hours postoperatively
Change in Tumor Necrosis Factor-alpha (TNF-α) Level
Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.
Measured: Baseline, 48 to 72 hours postoperatively
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.
Measured: Baseline, 48 to 72 hours postoperatively
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.
Measured: Baseline, 48 to 72 hours postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2021
- Study start6 Aug 2021
- Primary completion22 Jun 2023
- Study completion22 Jun 2023
Why it stopped: This clinical trial was terminated on June 7, 2024 due to new information about contraindications of using the study drug in this population.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hyperglycemia StressStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Principal investigator, Georgia Davis, Emory University
- Investigators
- Georgia Davis, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04862234
- Sponsor's protocol ID
- IRB00097659
- Other IDs
- K23DK122199
- Status last verified
- Dec 2024
- First submitted
- 23 Apr 2021
- Last updated
- 17 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in the publication for this study (including text, tables, figures, and appendices) will be available to other researchers, after deidentification.
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Stress Hyperglycemia in General and Vascular Surgery Patients
- ClinicalTrials.gov ID
- NCT04862234
- Acronym / sponsor ID
- IRB00097659
- Conditions
- Hyperglycemia Stress
- Keywords
- Perioperative, Surgery, Stress Hyperglycemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This clinical trial was terminated on June 7, 2024 due to new information about contraindications of using the study drug in this population.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 6 Aug 2021 (actual)
- Primary completion
- 22 Jun 2023 (actual)
- Study completion
- 22 Jun 2023 (actual)
- First posted
- 27 Apr 2021 (actual)
- Results
- Posted 17 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dulaglutide | Experimental | Drug: Dulaglutide, Device: Continuous glucose monitor (CGM), blindedParticipants randomized to receive dulaglutide within 72 hours prior to a planned surgery. |
| Placebo | Placebo comparator | Drug: Placebo, Device: Continuous glucose monitor (CGM), blindedParticipants randomized to receive a placebo to match dulaglutide within 72 hours prior to a planned surgery. |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DulaglutideAlso: TrulicityA subcutaneous injection of dulaglutide 0.75 mg will be administered within 72 hours prior to a planned surgical intervention. | Drug | Dulaglutide |
| PlaceboA subcutaneous injection of a saline placebo will be administered within 72 hours prior to a planned surgical intervention. | Drug | Placebo |
| Continuous glucose monitor (CGM), blindedAlso: FreeStyle Libre ProContinuous 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. | Device | Dulaglutide, Placebo |
Primary outcome
Percentage of Time in Target Glucose Range (70-140 mg/dL) by CGM
Time frame: During hospitalization (up to 5 days postoperatively)
The percentage of time in the target glucose range of 70-140 mg/dL, as measured by a continuous glucose monitor (CGM) data was determined.
16 secondary outcomes
Percentage of Time in Hyperglycemia (Glucose>140 mg/dL)
Time frame: During hospitalization (up to 5 days postoperatively)
Percentage of Time in Hyperglycemia (Glucose>180 mg/dL)
Time frame: During hospitalization (up to 5 days postoperatively)
Percentage of Time in Hypoglycemia (Glucose <70 mg/dL)
Time frame: During hospitalization (up to 5 days postoperatively)
Percentage of Time in Hypoglycemia (Glucose <54 mg/dL)
Time frame: During hospitalization (up to 5 days postoperatively)
Percentage of Time in Hypoglycemia (Glucose <40 mg/dL)
Time frame: During hospitalization (up to 5 days postoperatively)
Mean Onset of Stress Hyperglycemia During the Postoperative Period
Time frame: During hospitalization (up to 5 days postoperatively)
Mean Duration of Stress Hyperglycemia During the Postoperative Period
Time frame: During hospitalization (up to 5 days postoperatively)
Mean Daily Glucose Values
Time frame: During hospitalization (up to 5 days postoperatively)
Maximum Daily Glucose Values
Time frame: During hospitalization (up to 5 days postoperatively)
Perioperative Insulin Requirements
Time frame: During hospitalization (up to 5 days postoperatively)
Change in Plasma Cortisol Level
Time frame: Baseline, 48 to 72 hours postoperatively
Change in Level of Free Fatty Acids (FFA)
Time frame: Baseline, 48 to 72 hours postoperatively
Change in High Sensitivity C-reactive Protein (hsCRP) Level
Time frame: Baseline, 48 to 72 hours postoperatively
Change in Tumor Necrosis Factor-alpha (TNF-α) Level
Time frame: Baseline, 48 to 72 hours postoperatively
Change in Adiponectin Level
Time frame: Baseline, 48 to 72 hours postoperatively
Change in Level of Thiobarbituric Acid Reactive Substances (TBARS)
Time frame: Baseline, 48 to 72 hours postoperatively
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in the publication for this study (including text, tables, figures, and appendices) will be available to other researchers, after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Georgia Davis, MD principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dulaglutide and Continuous glucose monitor (CGM), blinded in people with Hyperglycemia Stress, run by Emory University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Time in Target Glucose Range (70-140 mg/dL) by CGM (time frame: During hospitalization (up to 5 days postoperatively)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2025.