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

NCT ID: NCT05780905

Last Updated: 2024-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-11
• Study Completion Date: 2026-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Diabetes Mellitus, Type 2; Stroke (CVA) or Transient Ischemic Attack

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Subjects randomized to placebo for 1 year.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Active

Subjects randomized to semaglutide for 1 year.

Group Type: ACTIVE_COMPARATOR

Semaglutide Auto-Injector

Intervention Type: DRUG

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 times. They will be given a 0.5mg injector and a 1mg injector for use beginning 5 and 9 weeks from baseline respectively.

The target dose for subjects is 1mg per week up to the 52 week treatment duration.

Interventions

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 times. They will be given a 0.5mg injector and a 1mg injector for use beginning 5 and 9 weeks from baseline respectively.

The target dose for subjects is 1mg per week up to the 52 week treatment duration.

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Other Intervention Names

ozempic

Eligibility Criteria

Inclusion Criteria

1. Men and women 40-65 years of age

2. Subjects with type-2 diabetes >= 3 years and HbA1C 7%-10% with blood sugar control medications including insulin, metformin, sulfonylureas, or SGLT2 inhibitors

3. Medically stable

4. Has not received any investigational drug in the past 6 months

5. Willing to participate and sign informed consent.

Exclusion Criteria

1. Contraindication to MRI or contrast agent

2. eGFR<45 mL/min/1.73m2 (eGFR is a measurement of kidney function)

3. Currently treated with glucagon-like peptide-1 receptor antagonist (same drug class as study intervention)

4. Unable to perform home-glucose monitoring

5. Currently need more than 100 units of insulin daily

6. Uncontrolled hypertension with systolic blood pressure (SBP)>180 mmHg or diastolic blood pressure (DBP)>100 mmHg

7. LDL-C>130 mg/dL or not on stable statin therapy in the past 6 months

8. Treatment with pioglitazone in the past 3 months

9. History of pancreatitis

10. History of myocardial infarction, stroke or transient ischemic attack

11. History or family history of Medullary Thyroid Carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

12. Hypersensitivity to semaglutide or any of the product components

13. Participating in other clinical trial

14. 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Francis Kim

Professor, Division of Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francis Kim, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

University of Washington - Harborview Medical Center

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Francis Kim, MD

Role: CONTACT

fkim@u.washington.edu

206-744-8305

Facility Contacts

Francis Kim, MD

Role: primary

fkim@u.washington.edu

206-744-8305

Other Identifiers

U1111-1271-3352

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

STUDY00016594

Identifier Type: -

Identifier Source: org_study_id