Atheroma Progression and Vulnerability Under Continuous Glucose Monitoring

Study Overview
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Brief Summary
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The OPTIMAL is a single-center, randomized trial to evaluate the efficacy of CGM-based glycemic control on atheroma progression in T2DM patients with CAD by using serial intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) imaging. A total of 90 eligible subjects will be randomized 1:1 into 2 groups to receive either CGM-based glycemic control or HbA1c-baded glycemic management. Coronary angiography and NIRS/IVUS imaging is repeated at the end of the assigned treatment period. Results: The primary endpoint is the normalized absolute change in total atheroma volume from baseline to 12 months. The secondary endpoints include (1) the absolute change in percent atheroma volume, (2) the percent change in lipid core burden index, (3) the change in coefficient variance measured by CGM, (4) the change in atherogenic markers (high-density lipoprotein functionality, proprotein convertase subxilisin/kexin type 9 and fatty-acid binding proteins), and (5) the frequency of hypoglycemia. Safety will also be evaluated.

Detailed Description
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Enrollment of 90 patients is planned at National Cerebral & Cardiovascular Center in Japan. Study participants are randomly assigned to either CGM-based glucose management or HbA1c-based glucose management. Eligible subjects should have CAD requiring elective PCI. HbA1c at screening should be between 7.0 and 10.0%. Non-culprit vessel with its severe tortuousty and/or calcification will be excluded. Subjects with baseline estimated glomerular filtration rate <40 mL/min/1.73m2 will not be eligible. After informed consent has been obtained, elective PCI will be conducted to treat culprit lesion. NIRS/IVUS imaging will be conducted to evaluate coronary atheroma. In the CGM-based glucose management group, CGM (FreeStyle Libre Pro®, Abbott, Chicago, Illinoi, the United States) and HbA1c measurement will be undertaken at baseline and 3, 6, 9 and 12 months following PCI. In the HbA1c-based glucose management group, HbA1c will be measured at baseline and 3, 6, 9 and 12 months after PCI, and CGM will be used at baseline and 12 months in a similar fashion.. With regard to the use of anti-diabetic drugs, in the CGM-guided glycemic control group, endocrinologist will select glucose lowering drugs to fulfill the following CGM-derived goals: (a) the frequency of hypoglycemia=0%, (b) the coefficient of variation <36% and (c) averaged glucose level between 70-180 mg/dl.6 If the frequency of hypoglycemia is over 10% and/or the averaged glucose level is more than 400 mg/dl, patients will be asked to visit within 1 month after CGM measurement. In the HbA1c-guided therapy group, the selection of glucose lowering agents will be made according to the discretion of each endocrinologist to achieve HbA1c <7.0%. At 12 months following PCI, patients will be hospitalized to take follow-up coronary angiography and intravascular imaging study. NIRS/IVUS imaging in the non-culprit vessel will be conducted again in a similar fashion.

Official Title
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The Efficacy of Glycemic Control With Continuous Glucose Monitoring on Atheroma Progression: Rationale and Design of the Observation of Coronary Atheroma Progression Under Continuous Glucose Monitoring Guidance in Patients With Type 2 Diabetes Mellitus

Conditions
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Coronary Atherosclerosis

Intervention / Treatment
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* Device: continuous glucose monitoring (CGM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male of female between 20 and 85 years of age Type 2 diabetic patients with coronary artery disease who require PCI The presence of mild stenosis in the non-target vessel (% diameter stenosis between 10-50%) 7.0 ≤ HbA1c ≤ 10.0% HbA1c ≤ 10.0% in subjects who receive insulin, sulfonylurea or nateglinide Ability to understand the requirements of the study and to provide informed consent Exclusion Criteria: very tortuous coronary artery and/or severe calcification which is unsuitable for intravascular imaging Subjects with severe renal dysfunction (estimated glomerular filtration rate < 40 mL/min/1.73m2) the absence of any atherosclerotic lesions in the non-target vessel those who take PCSK9 inhibitor current enrolment in another investing device or drug study pregnancy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: HbA1c-guided group<br>Glycemic control is controlled by guideline-recommended HbA1c control. | |
| Active Comparator: CGM-guided group<br>Glycemic control is controlled by CGM-guided control. | Device: continuous glucose monitoring (CGM)<br>* CGM (FreeStyle Libre Pro®, Abbott, Chicago, Illinoi, the United States)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the normalized absolute change in total atheroma volume on serial intravascular ultrasound imaging. | This measure is analyzed by serial intravascular ultrasound imaging. | from baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the absolute change in percent atheroma volume on serial intravascular ultrasound imaging. | This measure is analyzed by serial intravascular ultrasound imaging. | from baseline to 12 months | 
| the percent change in lipid core burden index on serial near-infrared spectroscopy imaging. | This measure is analyzed by serial near-infrared spectroscopy imaging. | from baseline to 12 months | 
| the change in coefficient variance evaluated by CGM | This measure is analyzed by CGM. | from baseline to 12 months | 
| the correlation of change in concentration of serum proprotein convertase subxilisin/kexin type 9 with the normalized absolute change in total atheroma volume | The correlation of IVUS measure with concentration of serum proprotein convertase subxilisin/kexin type 9 is analyzed. | from baseline to 12 months | 
| change in TAV under the use of specific anti-diabetic agents (dipeptidyl peptidase-4 inhibitors, sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 agonists) | This measure is analyzed by serial intravascular ultrasound imaging. | from baseline to 12 months | 
| the frequency of hypoglycemia | This event is collected through each clinical visit. | from baseline to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes mellitus, coronary atherosclerosis, intravascular ultrasound, near-infrared spectroscopy, continuous glucose monitoring