Diabete Type 2
Conditions
Keywords
Semaglutide, Type 2 Diabetes Mellitus, MRI, C13 Hyperpolarized pyruvate
Brief summary
There has been a notable increase in the number of Canadians living with type II diabetes. People with this type of diabetes often have high levels of a substance called lactate in their blood, which might be linked to problems with thinking and heart failure. A new imaging technique has been developed that can help us see how lactate is being processed in the body. This involves using MRI technology to rapidly look at chemical reactions happening inside cells. This new method uses a special contrast agent that's injected into the body, which produces a much stronger magnetic signal, making it easier to see what's happening inside. In this study, we will use this new imaging method with a substance called carbon-13 pyruvate to monitor how it changes in the brain and heart of people with type II diabetes. We will also see how these changes relate to their treatment with a medication called semaglutide. This new MRI method has been used to study cancer, the brain and heart in human participants, but not in T2DM patients. The data we collect might help doctors improve the treatment of patients with T2DM, heart failure, dementia, and cognitive problems in the future. Health Canada has not approved the use of 13C-enriched pyruvate for use or sale for any condition, although they have allowed its use in this research study.
Detailed description
This study aims to see how well hyperpolarized 13C-pyruvate works to image the brain and heart of T2DM patients taking semaglutide, compared to those not taking it. Group 1: You will undergo two heart MRI scans. The first scan will take place before you begin taking semaglutide (referred to as Day 1). The second scan will occur at least 4 months after starting semaglutide. Both scans will use a special 13C pyruvate injection as a contrast agent. These MRI scans should take about 60 to 75 minutes each. Group 2: You will undergo two brain MRI scans. The first scan will take place before you begin taking semaglutide (referred to as Day 1). The second scan will occur at least 4 months after starting semaglutide. Both scans will use a special 13C pyruvate injection as a contrast agent. These MRI scans should take about 60 to 75 minutes each. Group 3: You will undergo two heart MRI scans. The first scan will be scheduled for a specific date, agreed upon by you and the research team (referred to as Day 1). The second scan will take place at least four months after the initial scan. Both scans will use a special 13C pyruvate injection. These MRI scans should take about 60 to 75 minutes each. Group 4: You will undergo two brain MRI scans. The first scan will be scheduled for a specific date, agreed upon by you and the research team (referred to as Day 1). The second scan will take place at least four months after the initial scan. Both scans will use a special 13C pyruvate injection. Each MRI scan should take about 60 to 75 minutes. All participants will complete standard cognitive tests within five days prior to each scan, (two assessments in total) to evaluate brain function. Alternatively, these tests may be performed on the day of the scan, prior to the procedure. Blood samples will be collected before each scan for a total of two samples. Blood samples will be stored in a secure, access-controlled laboratory freezer at Sunnybrook Research Institute. Each sample will be labeled with a unique study code and will not contain any directly identifying information. A master code list linking study codes to participant identifiers will be stored separately in a password-protected file on a secure server, accessible only to the principal investigator and authorized study staff. Upon completion of the study and after the retention period of 15 years, all remaining blood samples will be destroyed in accordance with Sunnybrook Research Institute biosafety procedures to ensure that samples cannot be reused or linked back to participants. All clinical procedures will be completed at Sunnybrook Health Sciences Centre (SHSC).
Interventions
DRUGC13 Hyperpolarized pyruvate injection
Participants will be injected with a 0.1 mmol/kg dose of hyperpolarized 13C pyruvate that is used as a contrast agent. The investigational medicinal product (IMP) hyperpolarized 13C pyruvate will be intravenously injected at a rate of 4 ml/second, followed by a 25 ml saline flush at 5 ml/second. Following injection, axial 3D gradient echo 13C sequences will be acquired using the applicable 13C imaging coil.
Sponsors
Sunnybrook Health Sciences Centre
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This is a pilot study in patients with type II Diabetes Mellitus using control groups
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult participants of all ethnic groups/race categories (≥ 18 years of age) * Blood lactate ≥ 2 mmol/L ≤ 5 mmol/L * Blood pressure target \< 130/80 * No history of macrovascular or microvascular disease * For participants in Groups 1 and 2: Prescribed a semaglutide dose of 0.5 mg S/C weekly * For participants in Groups 3 and 4: HbA1c between 7-9% on evidence-based medications as per the Diabetes Canada guidelines, but not GLP-1RA semaglutide * Written informed consent
Exclusion criteria
* History of macrovascular or microvascular disease * Automatic implantable cardiac-defibrillators (AICD) or pacemaker, either at time of study or required within 3 months of the study * Participants on anticonvulsants, benzodiazepines, immunosuppressants and/or antiarrhythmics * Any clinically significant or unstable medical condition that might limit their ability to complete the study * Any malignancy not considered cured, except basal cell carcinoma of the skin * Body mass index greater than 40.0 * Claustrophobia and/or inability to undergo MRI without sedation * Contraindications to MRI as indicated on the standard MRI safety screening questionnaire * Participant declines or is unable to
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the 13C-pyruvate | At baseline and during the second MRI scan | To measure changes in 13C-pyruvate in individual anatomical regions of the heart and brain by comparing pre- and post-semaglutide scans. |
| Changes in 13C-lactate | At baseline and during the second MRI scan | To measure the changes in 13C-lactate in individual anatomical regions of the heart and brain by comparing pre- and post-semaglutide scans. |
| Change in 13C-bicarbonate | At Baseline and during the second MRI scan | To measure the changes in 13C-bicarbonate in individual anatomical regions of the heart and brain by comparing pre- and post-semaglutide scans. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The difference in 13C-pyruvate between groups | At baseline and during the second MRI scan | To measure the difference in 13C pyruvate between groups in anatomical regions of the heart and brain by comparing pre- and post-semaglutide scans. |
| The difference in 13C-lactate between groups | At baseline and during the second MRI scan | To measure the difference in 13C-lactate between groups in anatomical regions of the heart and brain by comparing pre- and post-semaglutide scans. |
| The difference in 13C-bicarbonate between groups | At baseline and during the second MRI scan | To measure the difference in 13C-bicarbonate between groups in anatomical regions of the heart and brain by comparing pre- and post-semaglutide scans. |
Contacts
CONTACTNorberto Garcia
PRINCIPAL_INVESTIGATORCharles Cunningham, BASc, PhD
Sunnybrook Health Sciences Centre
Outcome results
None listed