Continuous Glucose Monitoring and Insulin for Ketosis-Prone Diabetes

Recruiting at 1 trial location

Overseen By Priyathama Vellanki, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Disqualifiers: Heart failure, Renal insufficiency, Liver insufficiency, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 months

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand daily changes in blood sugar levels in individuals with ketosis-prone diabetes, a form of diabetes where the body produces high levels of acids called ketones. Continuous glucose monitors will be used to adjust insulin doses, guiding patients toward remission. The trial targets African Americans who have experienced diabetic ketoacidosis, a serious complication involving very high blood sugar and ketones, and who have a BMI of 28 or higher. Participants will wear a glucose monitor to track blood sugar levels and adjust insulin as needed. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, helping to determine how it benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for insulin used in this trial?

Research has shown that insulin treatment is safe for people with diabetes. One study found that injecting insulin under the skin is a safe alternative to delivering it directly into a vein for treating diabetic ketoacidosis (DKA), a serious diabetes complication. This indicates that insulin is generally well-tolerated.

Another study highlighted the safety of automated insulin delivery systems, which automatically adjust insulin doses based on continuous glucose monitoring (CGM) data. This method is not only effective but also safe compared to traditional insulin treatments.

The insulin used in this trial is similar to what the FDA has already approved for managing diabetes, indicating a well-known safety record. While insulin is generally safe, it is important to follow dosing instructions and regularly check blood sugar levels to avoid complications. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the approach of using continuous glucose monitoring (CGM) with adjusted insulin doses for ketosis-prone diabetes because it offers a more personalized and responsive way to manage blood sugar levels. Unlike traditional methods that rely on periodic fingerstick tests, CGM provides real-time glucose readings, allowing for more precise insulin adjustments. This can lead to better glucose control and potentially reduce the risk of complications associated with erratic blood sugar levels. By tailoring insulin doses based on continuous data, this method could improve the overall management of ketosis-prone diabetes and enhance patients' quality of life.

What evidence suggests that continuous glucose monitoring with adjusted insulin doses is effective for ketosis-prone diabetes?

Research has shown that using continuous glucose monitoring (CGM) with adjusted insulin doses improves blood sugar control. In this trial, participants with ketosis-prone diabetes will use CGM systems to adjust insulin doses based on glucose readings. Studies have found that CGM systems can lower HbA1c levels, a measure of average blood sugar over time. They also increase the time spent with blood sugar in the target range, which is crucial for managing diabetes. Adjusting insulin based on CGM readings helps maintain stable blood sugar levels. This method is already known to be beneficial for managing diabetes, especially for those who need tight blood sugar control. ^{2 6 7 8 9}

Who Is on the Research Team?

Priyathama Vellanki, MD, MS

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for individuals with ketosis-prone diabetes (KPDM), a condition where the body produces high levels of blood acids called ketones. Participants should be experiencing this for the first time or have a history of similar episodes but not on long-term insulin therapy.

Inclusion Criteria

Meet diagnostic criteria for DKA. Diagnostic criteria for DKA will include a plasma glucose > 250 mg/dl, a venous pH < 7.30, a serum bicarbonate < 18 mmol/l, and serum ketones (beta-hydroxy butyrate) > 1.5 mmol/L.

Be of African American ancestry

My BMI is 28 or higher.

Exclusion Criteria

I was diagnosed with diabetes more than 90 days before my DKA episode.

Pregnant

I have an untreated hormone disorder like high cortisol, acromegaly, or overactive thyroid.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard-of-care insulin therapy and continuous glucose monitoring from hospital discharge until insulin discontinuation

Up to 3 months

Continuous monitoring with regular adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on remission duration

6 to 120 months

What Are the Treatments Tested in This Trial?

Interventions

• Insulin

Trial Overview The study is monitoring day-to-day blood sugar levels using Continuous Glucose Monitoring systems and treating participants with insulin to understand how KPDM goes into remission and to develop a mathematical model describing this process.

How Is the Trial Designed?

Group I: Continuous Glucose Monitoring with Adjusted Insulin Doses Experimental Treatment 2 Interventions

Patients with ketosis-prone diabetes will wear a continuous glucose monitor (CGM) from the time of hospital discharge until insulin discontinuation. Insulin doses will be adjusted based on CGM glucose readings.

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

Approved in European Union as Insulin for:

• Diabetes mellitus

Approved in United States as Insulin for:

• Diabetes mellitus

Approved in Canada as Insulin for:

• Diabetes mellitus

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

A comprehensive review of 50 studies over the past 20 years revealed significant differences in bioactivity between human insulin and various insulin analogues, affecting metabolism, cell growth, and other cellular functions.

The clinical implications of these differences in bioactivity are still unclear and require further investigation to understand their impact on different patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years. Werner, H., Chantelau, EA.[2021]

A comparison of insulin lispro and regular human insulin (Humulin R) in 3634 patients with type 1 and type 2 diabetes showed no significant differences in treatment-emergent adverse events, indicating similar safety profiles for both insulins.

Both insulin therapies did not differ in their effects on the progression of chronic diabetes complications, such as retinopathy, neuropathy, cardiovascular disease, or kidney disease, suggesting that insulin lispro is as safe as Humulin R.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of insulin lispro: pooled data from clinical trials. Glazer, NB., Zalani, S., Anderson, JH., et al.[2019]

The focus of insulin therapy has shifted from merely providing insulin to mimicking natural insulin secretion, which is crucial for preventing long-term complications of diabetes; this includes using fast-acting and long-acting insulin analogues to better control blood glucose levels.

Advancements in technology, such as continuous insulin pumps and glucose sensors, are improving blood glucose stability and may lead to semi-automated insulin delivery systems, enhancing the management of diabetes beyond traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Insulin substitution: new insulins, new modes of delivery]. Renard, E.[2019]

Humalog, evaluated in 2834 patients across eight international studies, showed significant improvements in postprandial glycaemic control and a reduction in hypoglycaemic episodes, particularly at night, despite no significant decrease in overall HbA1C levels.

In a crossover study, patients using Humalog experienced five times fewer severe hypoglycaemic episodes compared to those on standard treatment, indicating its potential for safer diabetes management, although intensive treatment with multiple injections is recommended for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The insulin analog, Humalog, in discontinuous: from pharmacology to clinical use]. Tauber, JP.[2011]

Short-acting insulin analogues like lispro, aspart, and glulisine provide faster action and better post-meal blood sugar control without increasing the risk of hypoglycemia, allowing for administration just before meals.

Long-acting insulin analogues such as glargine and detemir offer stable insulin levels for up to 24 hours with a lower risk of nighttime hypoglycemia, improving overall blood glucose management in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New developments in the treatment and monitoring of type 1 diabetes mellitus]. Otto-Buczkowska, E., Jarosz-Chobot, P., Tucholski, K.[2017]

In a study involving 10 type 1 diabetes patients, insulin lispro (Humalog) was found to enhance the liver's response to glucagon, leading to a greater increase in hepatic glucose production compared to regular human insulin (Humulin R).

This increased sensitivity to glucagon with insulin lispro may help reduce the risk of severe hypoglycemia in type 1 diabetes patients undergoing intensive insulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of continuous subcutaneous insulin infusion with lispro on hepatic responsiveness to glucagon in type 1 diabetes. Launay, B., Zinman, B., Tildesley, HD., et al.[2022]

In a study of 221 adults with type 1 diabetes, switching to ultra-long-acting insulin (degludec U100 and glargine U300) did not significantly change the incidence of diabetic ketoacidosis (DKA) episodes, indicating that this new insulin type may not reduce DKA risk.

Despite higher total daily insulin doses after switching to ultra-long-acting insulin, there was no significant change in glycated hemoglobin A1C (HbA1c) levels, suggesting that insulin type and dosage alone may not be sufficient to control diabetes effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Ultra-Long-Acting Insulin Compared to Long-Acting Insulin on Diabetic Ketoacidosis Incidence in Type 1 Diabetes Mellitus Patients. Alsofiani, WA., Alessa, BH., Alsabaan, F., et al.[2022]

Insulin detemir (Levemir) offers a long-acting and consistent insulin option for patients with type 1 or type 2 diabetes, providing a predictable effect with less variability in blood sugar control compared to NPH insulin.

It is at least as effective as NPH in managing overall blood sugar levels while reducing the risk of nocturnal hypoglycemia and causing less weight gain, making it a favorable choice for basal insulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Insulin detemir (Levemir)]. Scheen, AJ., Radermecker, RP., Philips, JC., et al.[2015]

Insulin remains the primary treatment for type 1 diabetes, but recent advancements in insulin analogues have significantly improved glycemic control and allowed for more physiological basal/bolus insulin regimens.

New basal insulin analogues, such as degludec, pegylated lispro, and glargine U300, have shown improvements in duration of action and reduced risk of hypoglycemia, addressing key challenges in intensive diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New insulin types in type 1 diabetes mellitus]. Mesa, J.[2015]

In a pilot study involving 19 adults using the MiniMed™ 670G system, both Novolog® and Fiasp® insulin showed similar effectiveness in managing blood sugar levels, with no significant differences in time spent within the target glucose range or hypoglycemia rates.

Fiasp® required a slightly higher daily insulin dose compared to Novolog®, but both insulins resulted in comparable glycemic outcomes, indicating that either can be effectively used in a hybrid closed-loop system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fast-Acting Insulin Aspart Use with the MiniMedTM 670G System. Hsu, L., Buckingham, B., Basina, M., et al.[2022]

In a study involving 28 critical care patients, Humalog insulin (Hlog) demonstrated a significantly less profound carryover effect and shorter duration of action compared to Humulin insulin (Hlin), indicating it may lead to more stable blood glucose levels after treatment ends.

Hlog also resulted in a faster drop in blood glucose during infusion and a quicker rise after discontinuation, suggesting it could be a more effective option for insulin infusion therapy in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin infusion therapy in critical care patients: regular insulin vs short-acting insulin. A prospective, crossover, randomized, multicenter blind study. Bilotta, F., Badenes, R., Lolli, S., et al.[2018]

In a study involving 112 children and adolescents with type 1 diabetes, the combination of ultrashort acting insulin aspart with detemir or glargine showed a significant decrease in HbA1c levels, indicating improved blood sugar control over 12 and 24 weeks.

The use of detemir and glargine significantly reduced the risk of hypoglycemia compared to traditional NPH-insulin, while maintaining a stable body mass index in the detemir group, suggesting a safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Basal insulin analogue versus traditional NPH insulin in basal bolus therapy of children and adolescents with type 1 diabetes]. Prikhodina, OA., Surikova, SV., Girsh, YV.[2020]

Basal insulin is crucial for regulating glucose and fatty acid release, and in type 1 diabetes, traditional long-acting insulins like NPH are inadequate due to their peak effects, which can lead to hypoglycemia and hyperglycemia.

Continuous subcutaneous insulin infusion (CSII) and long-acting insulin analogs like glargine and detemir are recommended for better management of basal insulin in type 1 diabetes, as they provide a more stable insulin release, reducing the risk of hypoglycemia and improving blood glucose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the replacement of basal insulin in type 1 diabetes mellitus: no longer an elusive goal in the post-NPH era. Bolli, GB., Andreoli, AM., Lucidi, P.[2013]

In a 32-week study involving 686 patients with Type 2 diabetes, insulin detemir (IDet) therapy was found to be safe, with no serious adverse drug reactions reported and a significant reduction in total hypoglycemic events from 435 to 204.

Patients experienced improved glycemic control, as indicated by a decrease in glycated hemoglobin A1c from 9.9% to 7.7% and fasting plasma glucose from 11.9 mmol/L to 7.4 mmol/L, alongside a slight reduction in body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety of insulin detemir in patients with Type 2 diabetes in the Gulf countries: The multicenter, noninterventional, open-label LevSafe study. El Shiekh, AR., Farrag, HA., Ashour, T., et al.[2020]

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A mathematical model for ketosis-prone diabetes suggests ... Although KPD patients are initially insulin-dependent, after a few months of insulin treatment, roughly 70% undergo near-normoglycemia remission ...