Experimental Hyperglycemia for Type 1 Diabetes

Overseen By Anjali Kumar, PA-C

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must be taking: Insulin

Must not be taking: Glucocorticoids, Niacin

Disqualifiers: Pregnancy, Hypertension, Neuropathy, Retinopathy, others

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how certain brain functions change in people with type 1 diabetes who experience low blood sugar without the usual warning signs. Participants will undergo controlled episodes of high blood sugar (experimental hyperglycemia) to study these changes, with different target levels set for testing. The trial seeks individuals who have had type 1 diabetes for 2 to 30 years, maintain blood sugar levels under control (Hemoglobin A1C under 8.5%), and can feel when their blood sugar is low. As an unphased trial, this study offers a unique opportunity to contribute to scientific understanding and potentially improve future diabetes care.

Will I have to stop taking my current medications?

The trial requires that you stop taking drugs that can alter glucose metabolism, like glucocorticoids and niacin, but you can continue using insulin and other glucose-lowering drugs for diabetes.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that high blood sugar affects individuals differently depending on its duration and severity. This trial examines short-term high blood sugar, distinct from prolonged high levels. Long-term high blood sugar can cause issues like memory loss, but the effects of short-term elevations remain less understood.

Participants in this study will have their blood sugar temporarily raised in a controlled manner, which is generally safe in a medical setting. Researchers will closely monitor blood sugar levels throughout the study to manage any immediate risks or side effects.

Although specific safety data for this exact setup is unavailable, the trial's controlled and short-term nature suggests relative safety. By focusing on monitoring, researchers can quickly address any side effects, ensuring a safe experience for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the experimental hyperglycemia approach for Type 1 Diabetes because it explores a novel way of managing blood sugar levels by intentionally maintaining them at higher targets. Unlike traditional treatments that focus on tightly controlling blood sugar with insulin to avoid hyperglycemia, this method investigates the potential benefits of less stringent glucose control, aiming for targets such as 150 mg/dL, 225 mg/dL, and 300 mg/dL. This could reveal new insights into how different glucose targets impact overall health and diabetes management, potentially leading to more personalized treatment strategies.

What evidence suggests that this trial's treatments could be effective for impaired awareness of hypoglycemia?

This trial will explore different levels of experimental hyperglycemia in participants with type 1 diabetes, with separate treatment arms targeting blood sugar levels of 150 mg/dL, 225 mg/dL, and 300 mg/dL. Studies have shown that stable blood sugar levels are crucial for people with type 1 diabetes. Automated insulin delivery systems can help reduce episodes of low blood sugar. This suggests that controlled changes in blood sugar, such as temporarily raising it, could provide insights into how the brain responds to low blood sugar. Research also supports using continuous glucose monitoring to effectively track blood sugar changes. Although direct evidence is not yet available to show that temporarily raising blood sugar will improve awareness in type 1 diabetes, these studies highlight the importance of understanding blood sugar control in managing the condition. ^{6 7 8 9 10}

Who Is on the Research Team?

Elizabeth R Seaquist, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for people with Type 1 diabetes who've had it for 2-30 years and have a Hemoglobin A1C below 8.5%. It's not for those pregnant, with uncontrolled high blood pressure, substance abuse issues, unable to undergo MRI scans due to various reasons like claustrophobia or having certain implants, over 300 lbs., or with a history of serious heart conditions, depression requiring hospitalization, arrhythmias in the last five years.

Inclusion Criteria

Your average blood sugar level (Hemoglobin A1C) is less than 8.5%.

I have had diabetes for 2 to 30 years.

I have been diagnosed with Type 1 diabetes.

Exclusion Criteria

Unable to complete all study visits or procedures, as determined by the investigator

I am not taking medication that affects my blood sugar, except for diabetes treatment.

I have symptoms like dizziness when standing up or slow stomach emptying.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-study Monitoring

Participants' glycemic variability and activity/sleep are monitored for 1 week before each study

1 week

Induction of Hypoglycemia

Participants undergo three 2-hour long hypoglycemic clamps to induce impaired awareness of hypoglycemia

6 hours

Neurochemical Measurement

Neurochemical profiles are measured by high field MRS before and after induction of impaired awareness of hypoglycemia

1 session

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Experimental hyperglycemia

Trial Overview The study tests how repeated low blood sugar episodes affect the brain's ability to detect hypoglycemia in Type 1 diabetics. Participants will experience controlled low blood sugar events while their brain responses are monitored using advanced imaging techniques.

How Is the Trial Designed?

Group I: 300 mg/dL Experimental Treatment 1 Intervention

Hyperglycemia target of 300 mg/dL

Group II: 225 mg/dL Experimental Treatment 1 Intervention

Hyperglycemia target of 225 mg/dL

Group III: 150 mg/dL Experimental Treatment 1 Intervention

Hyperglycemia target of 150 mg/dL

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

A study analyzing FDA Adverse Event Reporting System data from January 2013 to March 2022 found that different DPP-4 inhibitors have varying risks for serious side effects, such as acute kidney injury and pemphigoid, which can guide treatment choices for diabetes patients.

Specifically, alogliptin showed a significantly lower risk of acute kidney injury compared to sitagliptin, but a higher risk of pemphigoid, highlighting the importance of selecting the appropriate DPP-4 inhibitor based on a patient's specific health concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Adverse Events Occurred During Administration of Dipeptidyl Peptidase-4 Inhibitor in Patients with Diabetes Using FDA Adverse Event Reporting System. Ogura, T., Shiraishi, C.[2023]

SGLT2 inhibitors significantly lower key diabetes markers in type 1 diabetes patients, including glycated hemoglobin (HbA1c) and fasting plasma glucose, while also reducing body weight and total insulin dosage, based on a meta-analysis of 16 randomized controlled trials involving 7192 patients.

Importantly, the use of SGLT2 inhibitors does not increase the risk of hypoglycemia, urinary tract infections, or diarrhea, suggesting they can be safely integrated into treatment regimens for type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium glucose cotransporter2 inhibitors for type 1 diabetes mellitus: A meta-analysis of randomized controlled trials. Nan, J., Wang, D., Zhong, R., et al.[2023]

Incretin-based therapies, including DPP-4 inhibitors and GLP-1 receptor agonists, provide effective glycemic control in type 2 diabetes with lower rates of hypoglycemia compared to other diabetes medications, based on a review of 112 clinical trials lasting at least 26 weeks.

The most common side effects were infections for DPP-4 inhibitors and gastrointestinal issues for GLP-1 receptor agonists, but serious concerns like pancreatitis and thyroid tumors were rare, indicating a favorable safety profile, though long-term safety monitoring is still necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of incretin-based therapies in type 2 diabetes. Evans, M., Bain, SC., Vora, J.[2019]

In a study of patients with type 1 diabetes, those using insulin glargine 300 U/mL (IG300) and insulin degludec (ID) showed similar long-term safety and efficacy compared to those continuing with insulin glargine 100 U/mL (IG100), with low rates of severe hypoglycemia and stable HbA1c levels over an average follow-up of 1.1 to 1.6 years.

Patients on IG100 experienced higher rates of severe adverse events and mortality (1.95%) compared to those on IG300 (0.7%) and ID (0.8%), suggesting that IG300 and ID may offer better safety profiles for long-term management of type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Treatment with New Basal Insulin Analogues in Type 1 Diabetes: Nation-Wide Survey. Svensson, AM., Ekelund, J., Miftaraj, M., et al.[2020]

Citations

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Real-World Analysis of Therapeutic Outcome in Type 1 ... Hypoglycaemia was less frequent (P<0.001), sensor-augmented therapy was more common (P=0.003) and mean body mass index (BMI) was higher (P=0.002) with CSII ...

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Glycometabolic outcomes in adult type 1 diabetic patients ... This study aimed to evaluate glycometabolic outcomes in AID technology-naïve T1D patients after switching to Hybrid Closed Loop (HCL) and Advanced Hybrid ...

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Data-driven blood glucose level prediction in type 1 diabetes Accurate prediction of blood glucose level (BGL) has proven to be an effective way to help in type 1 diabetes management.

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Predictive Hyperglycemia and Hypoglycemia Minimization The objective of this study was to determine the safety, feasibility, and efficacy of a predictive hyperglycemia and hypoglycemia minimization (PHHM) system

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Diabetes Management and Hyperglycemia in Safety ... Over the long term, chronic hyperglycemia is a risk for cognitive decline. Acute episodes of hyperglycemia, above 15 mmol/L have also been shown to affect ...

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Efficacy and safety of closed-loop control system for type ... CLC insulin delivery exhibits significantly better day and night efficacy and safety than SAP therapy in adolescents with type 1 diabetes.

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The Relation Between Hyperglycemia and Outcomes in 2471 ... OBJECTIVE— To examine whether hyperglycemia at the time of presentation was associated with outcomes in patients admitted to non–intensive care settings ...

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Efficacy and Safety of Automated Insulin Delivery Systems ... Patients on AID systems had more pronounced improvement of time below range when diabetes duration was more than 20 years (–1.80% vs. –0.86%, P= ...