Clinical trial NCT04559191: Atheroma Progression and Vulnerability Under Continuous Glucose Monitoring
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Coronary Atherosclerosis
Keywords: type 2 diabetes mellitus
coronary atherosclerosis
intravascular ultrasound
near-infrared spectroscopy
continuous glucose monitoring
Lead sponsor: National Cerebral and Cardiovascular Center, Japan
Sponsor class: OTHER
First posted: 2020-09-22
Enrollment: 90
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: the normalized absolute change in total atheroma volume on serial intravascular ultrasound imaging.
timeFrame: from baseline to 12 months
Secondary outcomes:
measure: the absolute change in percent atheroma volume on serial intravascular ultrasound imaging.
timeFrame: from baseline to 12 months
measure: the percent change in lipid core burden index on serial near-infrared spectroscopy imaging.
timeFrame: from baseline to 12 months
measure: the change in coefficient variance evaluated by CGM
timeFrame: from baseline to 12 months
measure: the correlation of change in concentration of serum proprotein convertase subxilisin/kexin type 9 with the normalized absolute change in total atheroma volume
timeFrame: from baseline to 12 months
measure: 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)
timeFrame: from baseline to 12 months
measure: the frequency of hypoglycemia
timeFrame: from baseline to 12 months
Other outcomes:
Locations:
city: Suita
country: Japan
facility: National Cerebral & Cardiovascular Center
Study officials:
affiliation: National Cerebral & Cardiovascular Center
name: Yu Kataoka, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kataoka Y, Hosoda K, Makino H, Matsubara M, Matsuo M, Ohata Y, Koezuka R, Tamanaha T, Tomita T, Honda-Kohmo K, Noguchi M, Son C, Nishimura K, Asaumi Y, Miyamoto Y, Noguchi T, Yasuda S. 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 (OPTIMAL). Cardiovasc Diagn Ther. 2019 Oct;9(5):431-438. doi: 10.21037/cdt.2019.09.02.