Effects of Semaglutide on Intracranial Blood Flow and Brain-Barrier Permeability in Type-2 Diabetes
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Intracranial blood flow (IBF)
研究概览
简要总结
A human subjects research study, the primary purpose of which is to assess the EFFECTS OF SEMAGLUTIDE ON INTRACRANIAL BLOOD FLOW AND BLOOD-BRAIN BARRIER PERMEABILITY IN TYPE-2 DIABETES (T2D) through testing of the intervention on patients in a clinical setting. The study will randomize subjects with diabetes to either semaglutide or matching placebo. Magnetic resonance images will be primary endpoint measured at baseline and at one year to assess effect of this FDA approved medication.
Given the available evidence supporting the neuroprotective effect of this drug class and stroke reduction with semaglutide, and the investigators preliminary data showing that T2D had significantly reduced total number of distal arterial branches in the brain than non-T2D, the investigators expect treatment with semaglutide will be associated with improved intracranial blood flow condition.
详细描述
The investigators preliminary data showed that T2D had significantly reduced total number of distal branches as assessed using the investigators quantitative magnetic resonance angiography (MRA) feature measurement method (iCafe) than non-T2D. This reduction represents a decrease in intracranial blood flow condition and can be an indication for ischemia. Clinical trial showed that semaglutide reduces stroke incidence in T2D. The investigators are conducting a randomized, double blind and placebo-controlled study to investigate the biological basis of the observed stroke reduction with semaglutide by demonstrating semaglutide can improve intracranial blood flow condition and reduce bloodbrain barrier (BBB) permeability. The investigators working hypothesis is that it is known that semaglutide has beneficial effects on T2D, therefore, it improves endothelial function for a better cerebral flow condition. However, semaglutide may also improve cerebral flow independently from glucose lowering. Together, the improved cerebral flow condition results in stroke reduction. In order to investigate the independent effects of semaglutide on intracranial blood flow condition and BBB permeability, the investigators will have a designated diabetes care specialist unblinded to the study randomization to carry out glucose management to achieve HbA1C<7.5% for both treatment groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women 40-65 years of age
- •Subjects with type-2 diabetes >= 3 years and HbA1C 7%-10% with blood sugar control medications including insulin, metformin, sulfonylureas, or SGLT2 inhibitors
- •Medically stable
- •Has not received any investigational drug in the past 6 months
- •Willing to participate and sign informed consent.
排除标准
- •Contraindication to MRI or contrast agent
- •eGFR<45 mL/min/1.73m2 (eGFR is a measurement of kidney function)
- •Currently treated with glucagon-like peptide-1 receptor antagonist (same drug class as study intervention)
- •Unable to perform home-glucose monitoring
- •Currently need more than 100 units of insulin daily
- •Uncontrolled hypertension with systolic blood pressure (SBP)>180 mmHg or diastolic blood pressure (DBP)>100 mmHg
- •LDL-C>130 mg/dL or not on stable statin therapy in the past 6 months
- •Treatment with pioglitazone in the past 3 months
- •History of pancreatitis
- •History of myocardial infarction, stroke or transient ischemic attack
- •History or family history of Medullary Thyroid Carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- •Hypersensitivity to semaglutide or any of the product components
- •Participating in other clinical trial
- •Women of child-bearing potential (ie, those who are not chemically or surgically sterilized or who are not post-menopausal) who have a positive pregnancy test at enrollment or who are breastfeeding or who plan to become pregnant in the next 15 months.
研究组 & 干预措施
Placebo
Subjects randomized to placebo for 1 year.
干预措施: Placebo (Other)
Active
Subjects randomized to semaglutide for 1 year.
干预措施: Semaglutide Auto-Injector (Drug)
结局指标
主要结局
Intracranial blood flow (IBF)
时间窗: Approximately 12 Months
measured as total length and number of distal vessels
bloodbrain barrier Ktrans
时间窗: Approximately 12 Months
measured by dynamic contrast-enhanced MRI
次要结局
- Inflammatory markers(Approximately 12 Months)
研究者
Francis Kim
Professor, Division of Cardiology
University of Washington