search
Back to results

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

Primary Purpose

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

Status
Not yet recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Semaglutide Auto-Injector
Placebo
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional screening trial for Diabetes Mellitus, Type 2

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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.

Sites / Locations

  • University of Washington - Harborview Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Active

Arm Description

Subjects randomized to placebo for 1 year.

Subjects randomized to semaglutide for 1 year.

Outcomes

Primary Outcome Measures

Intracranial blood flow (IBF)
measured as total length and number of distal vessels
bloodbrain barrier Ktrans
measured by dynamic contrast-enhanced MRI

Secondary Outcome Measures

Inflammatory markers
hsCRP, interleukin-6 and tumor necrosis factor -a

Full Information

First Posted
March 10, 2023
Last Updated
March 10, 2023
Sponsor
University of Washington
Collaborators
Novo Nordisk A/S
search

1. Study Identification

Unique Protocol Identification Number
NCT05780905
Brief Title
Effects of Semaglutide on Intracranial Blood Flow and Brain-Barrier Permeability in Type-2 Diabetes
Official Title
Effects of Semaglutide on Intracranial Blood Flow and Brain-Barrier Permeability in Type-2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 3, 2023 (Anticipated)
Primary Completion Date
March 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
Novo Nordisk A/S

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, Stroke (CVA) or Transient Ischemic Attack

7. Study Design

Primary Purpose
Screening
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind and placebo controlled MRI study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to placebo for 1 year.
Arm Title
Active
Arm Type
Active Comparator
Arm Description
Subjects randomized to semaglutide for 1 year.
Intervention Type
Drug
Intervention Name(s)
Semaglutide Auto-Injector
Other Intervention Name(s)
ozempic
Intervention Description
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
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Intracranial blood flow (IBF)
Description
measured as total length and number of distal vessels
Time Frame
Approximately 12 Months
Title
bloodbrain barrier Ktrans
Description
measured by dynamic contrast-enhanced MRI
Time Frame
Approximately 12 Months
Secondary Outcome Measure Information:
Title
Inflammatory markers
Description
hsCRP, interleukin-6 and tumor necrosis factor -a
Time Frame
Approximately 12 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Francis Kim, MD
Phone
206-744-8305
Email
fkim@u.washington.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francis Kim, MD
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Washington - Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francis Kim, MD
Phone
206-744-8305
Email
fkim@u.washington.edu
First Name & Middle Initial & Last Name & Degree
Francis Kim, MD

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs