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

Sponsor
University of Washington (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05780905
Collaborator
Novo Nordisk A/S (Industry)
50
Enrollment
1
Location
2
Arms
44.9
Anticipated Duration (Months)
1.1
Patients Per Site Per Month

Study Details

Study Description

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 our preliminary data showing that T2D had significantly reduced total number of distal arterial branches in the brain than non-T2D, we expect treatment with semaglutide will be associated with improved intracranial blood flow condition.

Condition or Disease Intervention/Treatment Phase
  • Drug: Semaglutide Auto-Injector
  • Other: Placebo
 Phase 4

Detailed Description

Our preliminary data showed that T2D had significantly reduced total number of distal branches as assessed using our 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. We propose to conduct 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. Our 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, we 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized, double-blind and placebo controlled MRI studyRandomized, double-blind and placebo controlled MRI study
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Screening
Official Title:
Effects of Semaglutide on Intracranial Blood Flow and Brain-Barrier Permeability in Type-2 Diabetes
Anticipated Study Start Date :
Apr 3, 2023
Anticipated Primary Completion Date :
Mar 31, 2026
Anticipated Study Completion Date :
Dec 31, 2026

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Subjects randomized to placebo for 1 year.

Other: Placebo
Placebo
Active Comparator: Active

Subjects randomized to semaglutide for 1 year.

Drug: 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.
Other Names:
  • ozempic

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Intracranial blood flow (IBF) [Approximately 12 Months]

      measured as total length and number of distal vessels

    2. bloodbrain barrier Ktrans [Approximately 12 Months]

      measured by dynamic contrast-enhanced MRI

    Secondary Outcome Measures

    1. Inflammatory markers [Approximately 12 Months]

      hsCRP, interleukin-6 and tumor necrosis factor -a

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Washington - Harborview Medical Center Seattle Washington United States 98104

    Sponsors and Collaborators

    • University of Washington
    • Novo Nordisk A/S

    Investigators

    • Principal Investigator: Francis Kim, MD, University of Washington

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Francis Kim, Professor, Division of Cardiology, University of Washington
    ClinicalTrials.gov Identifier:
    NCT05780905
    Other Study ID Numbers:
    • STUDY00016594
    • U1111-1271-3352
    First Posted:
    Mar 23, 2023
    Last Update Posted:
    Mar 23, 2023
    Last Verified:
    Mar 1, 2023
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:
    Ischemic Attack, Transient
    Diabetes Mellitus
    Diabetes Mellitus, Type 2

    Study Results

    No Results Posted as of Mar 23, 2023