Extended Insulin Bolus for Type 1 Diabetes

Overseen By Laya Ekhlaspour, MD

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must be taking: Insulin

Must not be taking: Non-insulin anti-diabetics

Disqualifiers: Severe hypoglycemia, DKA, Gastroparesis, 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

Compensation: Varies

Number of Visits: 2

Duration: 2 days

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study aims to evaluate whether the use of an extended bolus will improve glucose control with high-fat high protein meals using a closed-loop system. The new knowledge gained from this study may provide a method to allow for the proper administration of insulin over an extended period to mitigate the risk of prolonged hyperglycemia or early hypoglycemia.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot start any new non-insulin glucose-lowering medications during the trial.

Is extended insulin bolus safe for humans?

Insulin detemir (Levemir) has been shown to reduce the risk of low blood sugar episodes, especially at night, without causing weight gain, which suggests it is generally safe for humans. Additionally, biosimilar insulin lispro has demonstrated similar safety to its original version in adults with type 1 diabetes. ^{1 2 3 4 5}

How is the extended insulin bolus treatment different from other insulin therapies for Type 1 Diabetes?

The extended insulin bolus treatment is unique because it delivers insulin over a longer period compared to the standard bolus, which may help in better managing blood sugar levels during meals that are high in fat or protein, as these can cause delayed blood sugar spikes. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Extended Insulin Bolus for Type 1 Diabetes?

Research shows that insulin detemir (Levemir) and insulin glargine (Lantus), which are part of the insulin therapy, can improve blood sugar control and reduce the risk of low blood sugar episodes in people with type 1 diabetes. These insulins help maintain stable blood sugar levels, especially overnight, and improve quality of life without causing weight gain. ^{3 11 12 13 14}

Who Is on the Research Team?

Laya Ekhlaspour, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for teens (13-18) with Type 1 Diabetes who use a smartphone and the Control IQ closed-loop system. They must have an A1C over 6%, not be on new diabetes meds other than insulin, and agree to follow meal/study guidelines. It's not for those with severe diabetes complications, untreated thyroid issues, or certain chronic conditions.

Inclusion Criteria

I have been diagnosed with type 1 diabetes for over a year.

You are currently using the Control IQ closed-loop system.

Willing to abide by meal recommendations and study procedures

Exclusion Criteria

Pregnancy or lactation

Current illness that would interfere with participation in the study

I am currently receiving cancer treatment or taking steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive standard and extended insulin bolus for high-fat high-protein meals over two days

2 days

2 visits (in-person)

Follow-up

Participants are monitored for glucose control effectiveness and safety post-treatment

5 hours post-bolus

What Are the Treatments Tested in This Trial?

Interventions

• Extended bolus of insulin
• Standard bolus of insulin

Trial Overview The study tests if extending the time insulin is delivered after eating high-fat/protein meals can better control blood sugar in Type 1 Diabetics using a closed-loop system. Participants will try both standard and extended boluses of insulin to see which manages glucose levels more effectively.

How Is the Trial Designed?

Group I: High Fat High Protein (HFHP) Meal- standard then extended insulin bolus arm Experimental Treatment 1 Intervention

Subjects will receive standard meal bolus for breakfast on the first day and extended meal bolus on the second day.

Group II: High Fat High Protein (HFHP) Meal- extended then standard insulin bolus arm Experimental Treatment 1 Intervention

Subjects will receive extended meal bolus for breakfast on the first day and standard meal bolus on the second day of the study.

Extended bolus of insulin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as insulin for:

• diabetes mellitus in adults, adolescents and children aged 2 years and above

Approved in United States as insulin for:

• type 1 diabetes
• type 2 diabetes

Approved in Canada as insulin for:

• type 1 diabetes
• type 2 diabetes

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study involving 232 type 1 diabetic patients over 26 weeks, switching to insulin detemir from NPH insulin or glargine did not change HbA1c levels but significantly reduced fasting blood glucose variability and the risk of nighttime hypoglycemic episodes.

Insulin detemir improved patients' quality of life with only a slight increase in daily insulin doses and no associated weight gain, highlighting its safety and efficacy as a basal insulin option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Insulin detemir in the predictive study: results in patients with type 1 diabetes in the Belgian cohort]. Philips, JC., Scheen, AJ.[2022]

In a study involving 100 young patients with type 1 diabetes, switching to insulin glargine (Lantus) and insulin glulisine (Apidra) significantly reduced average HbA1c levels from 8.3% to 7.7% over 24 months, indicating improved blood sugar control.

The therapy was found to be safe, with no recorded cases of severe or nocturnal hypoglycemia, and it did not lead to the progression of microvascular complications, enhancing the overall quality of life for the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of human insulin analogues in young patients with type 1 diabetes mellitus: Results of the RESULT observational program on the use of insulin glargine (Lantus) in combination with insulin glulisine (Apidra) as a basal-bolus regimen]. Efremova, NV., Bolotskaya, LL., Atarshchikov, DS., et al.[2019]

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]

In a study of 746 patients with type 2 diabetes, those who added rapid-acting insulin (RAI) to their existing insulin glargine therapy showed better treatment persistence and adherence compared to those who switched to premixed insulin (PMX).

Both treatment strategies resulted in similar reductions in A1C levels and incidences of hypoglycemia, indicating that while the basal-bolus approach may be more sustainable, both methods are effective in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world outcomes of adding rapid-acting insulin versus switching to analog premix insulin among US patients with type 2 diabetes treated with insulin glargine. Miao, R., Wei, W., Baser, O., et al.[2021]

Long-acting basal insulins, such as insulin glargine and insulin detemir, provide effective glycemic control for type 1 and type 2 diabetes while reducing the risk of hypoglycemia compared to intermediate-acting insulins.

Newer insulins like insulin glargine 300 units/mL and ultra-long-acting insulin degludec offer longer durations of action and improved pharmacokinetic profiles, which may enhance glycemic control and patient outcomes in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The past, present, and future of basal insulins. Pettus, J., Santos Cavaiola, T., Tamborlane, WV., et al.[2022]

Insulin analogues like insulin lispro and insulin aspart have a more rapid onset and shorter duration of action compared to conventional human insulin, which may improve flexibility in managing blood sugar levels.

However, these analogues do not significantly change overall blood sugar control (measured by hemoglobin A1c levels) or reduce the risk of hypoglycemia compared to standard human insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on insulin analogues. [2019]

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]

In a one-year cost analysis of insulin treatments for Type 2 diabetes patients in Germany, insulin glargine (Lantus) was found to be significantly cheaper than insulin detemir (Levemir), with average annual treatment costs of €849 versus €1,334, respectively, resulting in savings of €486 per patient (36%).

Both insulin types demonstrated equivalent treatment efficacy in managing diabetes, suggesting that patients can achieve the same glycemic control while using the more cost-effective insulin glargine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of one-year costs of type 2 diabetes treatment with insulin glargine or insulin detemir in a basal supported oral therapy (BOT) in Germany. Pscherer, S., Dietrich, ES., Dippel, FW., et al.[2019]

In a phase 3 study involving 507 adults with type 1 diabetes, SAR342434 (SAR-Lis) demonstrated similar efficacy to insulin lispro-Humalog (Ly-Lis) in reducing HbA1c levels, confirming its noninferiority as a treatment option.

Both SAR-Lis and Ly-Lis showed comparable safety profiles, with no significant differences in hypoglycemic events, treatment-emergent adverse events, or immunogenicity over a 12-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 1 Diabetes Also Using Insulin Glargine-SORELLA 1 Study. Garg, SK., Wernicke-Panten, K., Rojeski, M., et al.[2022]

In a study of 565 women treated with onabotulinumtoxinA for overactive bladder, there was no significant difference in urinary retention requiring clean intermittent catheterization between diabetic patients (5.8%) and non-diabetic patients (9%).

However, diabetic patients had a higher rate of urinary tract infections (UTIs) post-procedure (38.1% vs. 27.6%), and the presence of diabetes-related complications was linked to an increased risk of UTIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Correlation of Diabetes Mellitus and Urinary Retention From Intravesical OnabotulinumtoxinA Injection for Overactive Bladder. Takashima, Y., Handler, S., Laus, K., et al.[2023]

In a pooled analysis of two Phase III studies involving 374 participants, treatment with 50 U of abobotulinumtoxinA (aboBoNT-A) solution resulted in 88% of subjects experiencing none-or-mild glabellar lines one month after treatment, with effects lasting up to 6 months.

The treatment was well tolerated, with mostly mild or moderate nonserious adverse events, and showed high subject satisfaction regarding both appearance and psychological well-being compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid AbobotulinumtoxinA: Pooled Data From Two Double-Blind, Randomized, Placebo-Controlled Phase III Studies of Glabellar Line Treatment. Hilton, S., Kestemont, P., Sattler, G., et al.[2022]

Botulinum toxin type A (BoNTA) is recommended for managing refractory idiopathic Overactive Bladder, with guidelines emphasizing the importance of treating urinary tract infections before injection and ensuring patients can self-catheterize.

The injection procedure should be performed under local anesthesia in a controlled setting, with specific techniques to minimize risks, such as avoiding overfilling the bladder and monitoring patients post-injection for effective outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Guidelines for practical usage of botulinum toxin type A (BoNTA) for refractory idiopathic overactive bladder management]. Hermieu, JF., Ballanger, P., Amarenco, G., et al.[2017]

Botulinum toxin type A (BoNTA) is recommended for managing refractory idiopathic overactive bladder, with guidelines emphasizing the importance of treating urinary tract infections before injections and ensuring patients can self-catheterize.

The injection procedure should be performed under local anesthesia, with specific techniques to minimize risks, such as avoiding overfilling the bladder and monitoring patients post-injection to assess effectiveness and plan for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for practical usage of botulinum toxin type A (BoNTA) for refractory idiopathic overactive bladder management: Translation of French recommendations. Hermieu, JF., Ballanger, P., Amarenco, G., et al.[2014]

In a long-term study of up to 4 years involving patients with neurogenic detrusor overactivity, onabotulinumtoxinA consistently reduced urinary incontinence episodes by 3.2 to 4.1 episodes per day, significantly improving patients' quality of life.

The treatment showed a median duration of effect of 9 months, with common side effects being urinary tract infections and urinary retention, but no new safety concerns were identified over the study period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of onabotulinumtoxinA therapy are sustained over 4 years of treatment in patients with neurogenic detrusor overactivity: Final results of a long-term extension study. Kennelly, M., Dmochowski, R., Schulte-Baukloh, H., et al.[2022]

Citations

1. Belgium pubmed.ncbi.nlm.nih.gov

[Insulin detemir in the predictive study: results in patients with type 1 diabetes in the Belgian cohort]. [2022]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Use of human insulin analogues in young patients with type 1 diabetes mellitus: Results of the RESULT observational program on the use of insulin glargine (Lantus) in combination with insulin glulisine (Apidra) as a basal-bolus regimen]. [2019]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Basal insulin analogue versus traditional NPH insulin in basal bolus therapy of children and adolescents with type 1 diabetes]. [2020]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Real world outcomes of adding rapid-acting insulin versus switching to analog premix insulin among US patients with type 2 diabetes treated with insulin glargine. [2021]

5. England pubmed.ncbi.nlm.nih.gov

The past, present, and future of basal insulins. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Update on insulin analogues. [2019]

7. England 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. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Comparison of one-year costs of type 2 diabetes treatment with insulin glargine or insulin detemir in a basal supported oral therapy (BOT) in Germany. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 1 Diabetes Also Using Insulin Glargine-SORELLA 1 Study. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

The Correlation of Diabetes Mellitus and Urinary Retention From Intravesical OnabotulinumtoxinA Injection for Overactive Bladder. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Liquid AbobotulinumtoxinA: Pooled Data From Two Double-Blind, Randomized, Placebo-Controlled Phase III Studies of Glabellar Line Treatment. [2022]

12. France pubmed.ncbi.nlm.nih.gov

[Guidelines for practical usage of botulinum toxin type A (BoNTA) for refractory idiopathic overactive bladder management]. [2017]

13. France pubmed.ncbi.nlm.nih.gov

Guidelines for practical usage of botulinum toxin type A (BoNTA) for refractory idiopathic overactive bladder management: Translation of French recommendations. [2014]

14. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of onabotulinumtoxinA therapy are sustained over 4 years of treatment in patients with neurogenic detrusor overactivity: Final results of a long-term extension study. [2022]