Brain Glucose Transport Study for Type 2 Diabetes

Overseen By Elizabeth Sanchez Rangel, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Steroids, Illicit drugs

Disqualifiers: Uncontrolled hypertension, Neurological disorders, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how high blood sugar affects the brain in individuals with poorly controlled type 2 diabetes. Researchers aim to determine if better blood sugar management can resolve these issues. Participants will undergo tests, such as magnetic resonance spectroscopy (a type of brain scan), to observe changes in glucose transport in the brain. The study seeks individuals with a history of high blood sugar levels and a willingness to improve their diabetes care.

As an unphased trial, this study provides a unique opportunity to contribute to understanding diabetes' impact on the brain and potentially enhance personal diabetes management.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must be willing to follow an intensified diabetes management plan, which might involve changes to your current diabetes treatment.

What prior data suggests that this method is safe for studying brain glucose transport in individuals with Type 2 Diabetes?

Research shows that Magnetic Resonance Spectroscopy (MRS) is a safe and non-invasive method to study the brain. Studies have found that MRS provides important details about brain chemicals, aiding in the understanding of conditions like diabetes. Participants need not worry about harmful side effects, as MRS uses magnetic fields and radio waves, similar to an MRI scan.

Participants in past studies have generally tolerated MRS well, with no major reports of negative effects. This makes it a reliable and safe method for examining glucose movement in the brain, especially for those with type 2 diabetes. Thus, MRS is a good choice for anyone considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Brain Glucose Transport Study for Type 2 Diabetes because it aims to explore how glucose is transported to the brain, specifically the occipital lobe, during high blood sugar events. Unlike standard treatments for Type 2 Diabetes, such as insulin therapy or oral medications like metformin, this study uses MRSI (Magnetic Resonance Spectroscopic Imaging) to provide detailed insights into brain metabolism. This technique could reveal new aspects of how diabetes affects the brain, potentially leading to novel treatment strategies that target brain health in diabetic patients. Understanding these mechanisms might open up new avenues for managing diabetes more effectively, especially for those with uncontrolled conditions.

What evidence suggests that this trial's treatment could be effective for Type 2 Diabetes?

Research has shown that Magnetic Resonance Spectroscopy (MRS) effectively measures changes in brain glucose levels. MRS detects changes in the body's chemistry without surgery. Studies have found that MRS identifies problems with glucose transport in the brain, especially in people with type 2 diabetes. In this trial, participants will undergo MRS to measure brain glucose transport specifically in the occipital lobe during acute hyperglycemia. This allows researchers to assess how well glucose enters the brain and whether better glucose control helps. Overall, MRS provides valuable insights into how diabetes affects the brain and helps evaluate the benefits of improving glucose control. ^{6 7 8 9 10}

Who Is on the Research Team?

Elizabeth Sanchez Rangel, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with Type 2 diabetes who have high blood sugar levels (HbA1c > 7.5%) and a BMI of at least 18 kg/m2. Participants must consent to the study's procedures, be available throughout its duration, and agree to intensify their diabetes management.

Inclusion Criteria

I have a history of Type 2 diabetes.

I have a history of Type 2 diabetes.

I am willing and able to follow all study rules and attend all appointments.

Exclusion Criteria

I am not pregnant, trying to get pregnant, or breastfeeding.

Illicit drug use

I have a diagnosed neurological disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Pre-Treatment

Placement of a continuous glucose monitor (CGM) 2 weeks before the first magnetic resonance spectroscopy (MRS) at week 0

2 weeks

1 visit (in-person)

Treatment

Intensification of diabetes management and nutrition visits, with a second MRS at week 12

12 weeks

Multiple visits/phone calls

Follow-up

Participants are monitored for changes in brain glucose transport and glycemic control

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MRSI

Trial Overview The study uses Magnetic Resonance Spectroscopy Imaging (MRSI) to see if brain glucose transport changes in people with uncontrolled Type 2 diabetes can be reversed by improving blood sugar control over a period of three months.

How Is the Trial Designed?

Group I: Aim 1 Experimental Treatment 3 Interventions

Intervention before and after study with subjects with uncontrolled T2DM to measured brain glucose transport specifically in the occipital lobe during acute hyperglycemia

MRSI is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Magnetic Resonance Spectroscopy Imaging for:

• Diagnostic imaging for various conditions including brain disorders

Approved in European Union as Magnetic Resonance Spectroscopy Imaging for:

• Diagnostic imaging for various conditions including neurological disorders

Approved in Canada as Magnetic Resonance Spectroscopy Imaging for:

• Diagnostic imaging for various conditions including brain disorders

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

A meta-analysis of 10 studies involving 244 patients with type 2 diabetes mellitus (T2DM) revealed significant changes in brain metabolites, including decreased N-Acetyl Aspartate (NAA) levels and increased choline (Cho) and myo-inositol (MI) levels in various brain regions, indicating potential metabolic disturbances associated with T2DM.

These metabolite alterations, observed through proton magnetic resonance spectroscopy (MRS), suggest a link between brain chemistry changes and clinical symptoms in T2DM, highlighting the importance of understanding these changes for better management of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in cerebral metabolites in type 2 diabetes mellitus: A meta-analysis of proton magnetic resonance spectroscopy. Wu, GY., Zhang, Q., Wu, JL., et al.[2018]

In a study of eight children with type 1 diabetes, MRI scans revealed abnormal signals in the frontal brain region, indicating potential cerebral edema, particularly in those presenting with diabetic ketoacidosis (DKA).

The study found increased levels of taurine, myoinositol, and glucose in the brain, suggesting that these metabolic changes may contribute to the vulnerability of diabetic children to cerebral complications during DKA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insights into the acute cerebral metabolic changes associated with childhood diabetes. Cameron, FJ., Kean, MJ., Wellard, RM., et al.[2016]

An advanced magnetic resonance spectroscopy (MRS) protocol was developed that significantly improved the measurement of brain metabolites, achieving a 60% increase in signal-to-noise ratio using BaTiO3 dielectric padding, which enhances data quality during scans.

This protocol successfully monitored changes in neurotransmitter levels, showing reliable detection of decreased glucose and a trend of lower glutamate levels during hypoglycemia in patients with type 1 diabetes, facilitating better understanding of brain responses to glycemic changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring the Neurotransmitter Response to Glycemic Changes Using an Advanced Magnetic Resonance Spectroscopy Protocol at 7T. Park, YW., Deelchand, DK., Joers, JM., et al.[2022]

In a study using 1H magnetic resonance spectroscopy on Zucker Diabetic Fatty rats, significant increases in hippocampal glucose, myo-inositol, and total creatine levels were observed, indicating metabolic changes associated with type 2 diabetes.

The findings suggest that elevated levels of glucose and myo-inositol in the brain may reflect similar changes seen in human patients with diabetes, highlighting potential metabolic markers for the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic profile of the hippocampus of Zucker Diabetic Fatty rats assessed by in vivo 1H magnetic resonance spectroscopy. van der Graaf, M., Janssen, SW., van Asten, JJ., et al.[2006]

In a study involving 14 patients with poorly controlled diabetes and 14 healthy volunteers, brain glucose concentrations were found to be lower in diabetic patients, but the difference was not statistically significant, suggesting that chronic hyperglycemia may not affect brain glucose levels in humans.

The study utilized proton magnetic resonance spectroscopy to measure glucose levels in the occipital cortex at a plasma glucose level of 300 mg/dL, indicating that even with high blood sugar, brain glucose concentrations remained similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain glucose concentrations in poorly controlled diabetes mellitus as measured by high-field magnetic resonance spectroscopy. Seaquist, ER., Tkac, I., Damberg, G., et al.[2022]

In a study involving 11 mice with GL261 gliomas, acute hyperglycemia significantly increased glucose levels in brain tumors during hypothermia, with levels rising to an average of 1.6-fold, indicating a metabolic response to temperature changes.

Ex vivo analysis showed even greater glucose increases (up to 6.6-fold) in specific tumor regions during acute hyperglycemia, highlighting the heterogeneity of brain tumors and their varying responses to metabolic challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1H-MRSI pattern perturbation in a mouse glioma: the effects of acute hyperglycemia and moderate hypothermia. Simões, RV., Delgado-Goñi, T., Lope-Piedrafita, S., et al.[2010]

In a study involving 7 subjects, insulin did not significantly affect brain glucose concentrations during hyperglycemic clamp studies, suggesting that brain glucose metabolism is largely independent of insulin.

The research utilized advanced (1)H-magnetic resonance spectroscopy to measure glucose levels in different brain regions, confirming a linear relationship between plasma and brain glucose, and indicating that most cerebral glucose uptake occurs without insulin involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of insulin on in vivo cerebral glucose concentrations and rates of glucose transport/metabolism in humans. Seaquist, ER., Damberg, GS., Tkac, I., et al.[2019]

This study used proton magnetic resonance spectroscopy (1H-MRS) to show that brain lactate levels significantly increase during visual stimulation, indicating a broader role for lactate in brain energy metabolism.

Variations in blood glucose levels did not affect the lactate response during visual stimulation, suggesting that the brain's lactate response is stable across normal glucose ranges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: a proton magnetic resonance spectroscopy study at 1.5 Tesla. Maddock, RJ., Buonocore, MH., Lavoie, SP., et al.[2018]

Proton magnetic resonance spectroscopic imaging (1H-MRSI) at 7T offers a safer and more effective way to study brain glucose metabolism compared to deuterium MRSI (2H-MRSI), with better sensitivity and spatial resolution.

In a study involving five volunteers, 1H-MRSI successfully differentiated various metabolites, including glutamate and glucose, which could enhance our understanding of glucose metabolism's role in neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1H magnetic resonance spectroscopic imaging of deuterated glucose and of neurotransmitter metabolism at 7 T in the human brain. Bednarik, P., Goranovic, D., Svatkova, A., et al.[2023]

This study demonstrates that it is feasible to measure glucose concentration changes in the human hypothalamus using a standard 3T MRI system and MR spectroscopy, with reliable results obtained during hyperglycemic conditions.

Increased glucose and taurine concentrations were observed in the hypothalamus during hyperglycemia, particularly in subjects with plasma glucose levels above 300 mg/dl, indicating a significant relationship between hypothalamic glucose levels and blood glucose concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of Hypothalamic Glucose Under Euglycemia and Hyperglycemia by MRI at 3T. Joers, JM., Deelchand, DK., Kumar, A., et al.[2018]

In a study involving 20 patients with type 2 diabetes mellitus (T2DM) and 22 control subjects, significant metabolic differences were found in the lenticular nuclei, with lower NAA/Cr ratios and higher Cho/Cr ratios in T2DM patients, indicating altered brain metabolism associated with the disease.

The study suggests that the lenticular nuclei are more affected by T2DM than the thalamus, as these metabolic changes were detected before any visible lesions appeared, highlighting the early impact of diabetes on brain health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolite differences in the lenticular nucleus in type 2 diabetes mellitus shown by proton MR spectroscopy. Lin, Y., Zhou, J., Sha, L., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3292308/

Magnetic Resonance Spectroscopy Studies of Human ... MRS studies were a key factor in elucidating the role of glucose transport in the mechanism of muscle insulin resistance in type 2 diabetes. Insulin ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8576452/

Identifying Type 2 Diabetic Brains by Investigating Disease ... The present study aims to investigate four methods to extract features from MRI, characterize imaging biomarkers, as well as identify subjects with T2DM and CI.

3. nature.com nature.com/articles/emm2014101

Use of in vivo magnetic resonance spectroscopy for ... Magnetic resonance spectroscopy (MRS), which is fundamentally similar to magnetic resonance imaging, can detect metabolic changes in vivo noninvasively.

4. mdpi.com mdpi.com/2218-1989/12/12/1223

Magnetic Resonance Imaging and Spectroscopy Methods ... This review provides an overview of current MR techniques to measure hepatic glucose metabolism and the insights obtained by the application of these techniques

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5846391/

Magnetic resonance spectroscopy reveals abnormalities of ... Our findings reveal pronounced metabolic abnormalities in the AD brain and strongly suggest that brain glucose merits further investigation as a candidate AD ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12313504/

Advances in in vivo magnetic resonance spectroscopy for ... Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Imaging (MRI) yield valuable metabolic information in a non-invasive way.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6127672/

Altered brain metabolites in patients with diabetes mellitus ... This review aims to discuss current MRS data describing brain metabolite levels in DM patients with or without complications.

8. diabetesjournals.org diabetesjournals.org/diabetes/article/60/5/1361/33631/Magnetic-Resonance-Spectroscopy-Studies-of-Human

Magnetic Resonance Spectroscopy Studies of Human ... MRS studies were a key factor in elucidating the role of glucose transport in the mechanism of muscle insulin resistance in type 2 diabetes.

9. sciencedirect.com sciencedirect.com/topics/medicine-and-dentistry/magnetic-resonance-spectroscopy-data-acquisition

Magnetic Resonance Spectroscopy Data Acquisition MRS data acquisition is defined as the process of obtaining localized magnetic resonance spectroscopy data, which involves steps such as coil selection, ...

10. ajnr.org ajnr.org/content/early/2023/06/29/ajnr.A7895

Exploratory Multisite MR Spectroscopic Imaging Shows ... Our pilot study suggests that MRSI differentiates GM and WM by NAA/Cr in this population, disease complications may lead to neuroaxonal loss in WM in children.