Effects of Semaglutide on Intracranial Blood Flow and Brain-Barrier Permeability in Type-2 Diabetes

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Semaglutide Auto-Injector
  Subjects have an equal chance of receiving semaglutide or placebo. Which treatment subjects receive is decided at random by a computer (purely by chance, like the tossing of a coin). Neither subjects, Study Site personnel nor image reviewers will know which treatment subjects are assigned to. The study drug must be taken weekly. The subject's other medications may be changed by the study's un-blinded Endocrinologist. At baseline subject will receive and take home 0.25mg injector for use 3 more
• Другое Placebo
  Placebo

Первичные конечные точки

• Intracranial blood flow (IBF) [Срок оценки: Approximately 12 Months]
• bloodbrain barrier Ktrans [Срок оценки: Approximately 12 Months]

Вторичные конечные точки (1)

• Inflammatory markers [Срок оценки: Approximately 12 Months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Скрининг

Центры проведения

США · 1 центр

• University of Washington - Harborview Medical Center — Seattle

Идентификаторы

NCT: NCT05780905 · STUDY00016594 · U1111-1271-3352

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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