Automated Insulin + Pramlintide Delivery for Type 1 Diabetes

(FCL Trial)

Overseen By Ahmad Haidar, PhD.

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must be taking: Insulin

Must not be taking: Antihyperglycemics, Glucocorticoids, Hydroxyurea

Disqualifiers: Gastroparesis, Pregnancy, Severe hypoglycemia, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 9 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The aim of this clinical trial is to investigate whether a fully automated Lyumjev-and-pramlintide delivery system improves glycemic outcomes in adults with type 1 diabetes. The main question we aim to answer is whether a Lyumjev-pramlintide fully closed loop system improves time in range compared to a hybrid closed loop system with carbohydrate counting. We also aim to find the optimal insulin to pramlintide ratio for glycemic control in the fully automated system. In this cross-over study, patients will undergo the following three interventions in a random order: (i) fully automated Lyumjev insulin-and-pramlintide (8 μg/u) (ii) fully automated Lyumjev insulin-and-pramlintide (10 μg/u) (iii) rapid automated Lyumjev insulin-and-placebo with carbohydrate-matched boluses For all interventions, participants will be required to wear two Ypsomed pumps programmed by our developed EuGlide system.

Do I need to stop my current medications to join the trial?

You may need to stop certain medications to join the trial. If you are currently using antihyperglycemic agents other than insulin, you must stop them for a specific period before participating. Also, if you are using medications that affect gastrointestinal motility or glucocorticoids, you may need to stop those as well.

What data supports the effectiveness of the drug for type 1 diabetes?

Research shows that pramlintide, when added to insulin therapy, helps improve blood sugar control and reduce body weight in people with type 1 diabetes. Additionally, pramlintide has been found to lower blood sugar spikes and is well-tolerated in adolescents with type 1 diabetes. ^{1 2 3 4 5}

Is the Automated Insulin + Pramlintide Delivery System safe for humans?

Research shows that pramlintide, when used with insulin, is generally safe for people with type 1 diabetes. Studies have found it to be well-tolerated, meaning most people did not experience serious side effects. ^{1 3 4 6 7}

What makes the Fully Automated Insulin and Pramlintide Delivery System unique for type 1 diabetes?

This treatment is unique because it is a fully automated system that delivers both insulin and pramlintide without requiring meal input, which simplifies management by eliminating the need for carbohydrate counting while maintaining good blood sugar control. ^{1 4 7 8 9}

Research Team

Ahmad Haidar, Ph.D.

Principal Investigator

Research Institute of the McGill University Health Center

Laurent Legault, M.D.

Principal Investigator

Montreal's Children's Hospital Division of Endocrinology

Natasha Garfield, M.D.

Principal Investigator

Royal Victoria Hospital Division of Endocrinology

Michael Tsoukas, M.D.

Principal Investigator

Research Institute of the McGill University Health Center

Michael Vallis, Ph.D.

Principal Investigator

Dalhousie University Psychologist

Melissa-Rosina Pasqua, M.D.

Principal Investigator

Research Institute of the McGill University Health Center

Eligibility Criteria

Adults over 18 with type 1 diabetes using insulin pump therapy for at least three months can join. They must not have had diabetic ketoacidosis or severe hypoglycemia recently, be pregnant or breastfeeding, use certain diabetes medications like SGLT2I or GLP1-RA, and should agree to effective birth control if applicable.

Inclusion Criteria

I have been using an insulin pump for at least 3 months.

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

Individuals of childbearing potential using an effective birth-control method. An individual of childbearing potential must agree to use a highly effective method of birth control

Exclusion Criteria

Breastfeeding individuals

I do not have severe kidney, nerve, or eye problems.

I have been hospitalized for severe low blood sugar in the last month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Participants undergo a 5-day at-home run-in period before each intervention

5 days

Remote follow-up on days 2 and 5

Treatment

Participants undergo three interventions with different insulin-pramlintide ratios or placebo over three weeks each

9 weeks

Remote follow-up on days 2, 3, and 7 of each intervention

Washout

14-45 day washout period between interventions

14-45 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Fully Automated Insulin and Pramlintide Delivery System

Trial Overview The trial tests a fully automated system delivering insulin and pramlintide in different ratios (8 μg/u and 10 μg/u) against an automated system with insulin and placebo. The goal is to see which method keeps blood sugar levels within the target range best using two Ypsomed pumps.

Participant Groups

Group I: Fully automated Lyumjev-and-pramlintide delivery system (8 μg/u) Experimental Treatment 3 Interventions

Lyumjev and pramlintide fully automated delivery system with no meal announcement. Ratio of 1 unit of insulin for 8 μg of pramlintide.

Group II: Fully automated Lyumjev-and-pramlintide delivery system (10 μg/u) Experimental Treatment 3 Interventions

Lyumjev and pramlintide fully automated delivery system with no meal announcement. Ratio of 1 unit of insulin for 10 μg of pramlintide.

Group III: Hybrid automated Lyumjev-and-placebo delivery system with carbohydrate-matched boluses Active Control 1 Intervention

Lyumjev and saline placebo hybrid automated delivery system with meal announcement. Participants must input the carbohydrate content of their meals to inform the insulin bolus doses based on their pre-programmed insulin-to-carbohydrate ratios.

Fully Automated Insulin and Pramlintide Delivery System is already approved in United States, European Union for the following indications:

Approved in United States as Pramlintide for:

• Type 1 diabetes management when used with mealtime insulin

Approved in European Union as Pramlintide for:

• Type 1 diabetes management when used with mealtime insulin

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

Findings from Research

In a study involving 28 adults with type 1 diabetes, the novel fully closed-loop system using faster-acting insulin aspart (Fiasp) and pramlintide achieved a time in the glucose target range of 74.3%, which was not significantly inferior to the 78.1% achieved by the hybrid closed-loop system that required precise carbohydrate counting.

The fully closed-loop system resulted in fewer hypoglycemia events (33% of participants) compared to the hybrid system (58% of participants), suggesting it may offer a safety advantage despite not being statistically superior in overall glucose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fully artificial pancreas versus a hybrid artificial pancreas for type 1 diabetes: a single-centre, open-label, randomised controlled, crossover, non-inferiority trial. Tsoukas, MA., Majdpour, D., Yale, JF., et al.[2022]

The addition of pramlintide to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes significantly improved glycemic control, reducing HbA1c levels by -0.4% in the randomized controlled trial and -0.3% in the clinical practice trial, while also decreasing mealtime insulin doses by approximately 24% to 28%.

Pramlintide was found to be safe, with mild to moderate nausea being the most common side effect, and it did not increase the risk of severe hypoglycemia compared to placebo, making it a viable option for patients struggling to manage postprandial blood glucose levels and body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pramlintide improved measures of glycemic control and body weight in patients with type 1 diabetes mellitus undergoing continuous subcutaneous insulin infusion therapy. Herrmann, K., Frias, JP., Edelman, SV., et al.[2022]

In a study involving 12 adolescents with type 1 diabetes, pramlintide effectively reduced post-meal glucagon and glucose levels, indicating its potential to help manage blood sugar after eating.

Pramlintide was well tolerated with no adverse events reported, suggesting it is a safe option for this age group, but further long-term studies are needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pramlintide lowered glucose excursions and was well-tolerated in adolescents with type 1 diabetes: results from a randomized, single-blind, placebo-controlled, crossover study. Chase, HP., Lutz, K., Pencek, R., et al.[2022]

In a study involving 51 patients with type 1 diabetes, mixing pramlintide with short- or long-acting insulin in the same syringe did not significantly alter the pharmacokinetics or pharmacodynamics of either medication, indicating that this method of administration is safe and effective.

No unexpected adverse events or injection-site reactions were reported, suggesting that combining these injections is a safe option for patients managing their diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Properties of pramlintide and insulin upon mixing. Weyer, C., Fineman, MS., Strobel, S., et al.[2019]

In a 29-week study involving 296 patients with type 1 diabetes, pramlintide combined with reduced mealtime insulin effectively decreased postprandial glucose levels and weight, while both pramlintide and placebo groups showed similar reductions in HbA1c levels.

Although nausea was more common in the pramlintide group, it was mostly mild to moderate, and the rates of severe hypoglycemia were low in both groups, indicating that pramlintide can be a safe adjunct therapy for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled trial assessing pramlintide treatment in the setting of intensive insulin therapy in type 1 diabetes. Edelman, S., Garg, S., Frias, J., et al.[2022]

ADO09, a co-formulation of pramlintide and insulin A21G, significantly improved glycemic control in type 1 diabetes patients compared to insulin aspart, particularly in the high-dose group, with a 69% reduction in glucose increments after meals.

Patients using ADO09 experienced a significant reduction in body weight and improved time-in-range for blood glucose levels, although there were slightly more hypoglycemic and gastrointestinal events, which were generally transient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A co-formulation of pramlintide and insulin A21G (ADO09) improves postprandial glucose and short-term control of mean glucose, time in range, and body weight versus insulin aspart in adults with type 1 diabetes. Andersen, G., Eloy, R., Famulla, S., et al.[2023]

In a meta-analysis of 10 randomized placebo-controlled studies involving 3,297 participants, the addition of pramlintide to insulin therapy significantly improved glycemic control, reduced total daily insulin doses, and decreased body weight in patients with type 1 diabetes.

While pramlintide was effective, it also increased the risk of nausea, vomiting, anorexia, and transient hypoglycemia, particularly at the start of treatment, indicating the need for careful monitoring during initiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pramlintide injection adjunct to insulin therapy in patients with type 1 diabetes mellitus: a systematic review and meta-analysis. Qiao, YC., Ling, W., Pan, YH., et al.[2019]

A fully automated multihormone artificial pancreas, which combines insulin and pramlintide, showed comparable glycemic control to an insulin-only system in adults with type 1 diabetes, achieving similar time in target glucose range (81% vs 83%).

The iterative enhancements to the system, including adjustments to dosing algorithms and meal detection, indicate that while the multihormone approach can maintain glycemic control, further optimization is needed before proceeding to larger randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fully Automated Artificial Pancreas for Adults With Type 1 Diabetes Using Multiple Hormones: Exploratory Experiments. Majdpour, D., Tsoukas, MA., Yale, JF., et al.[2022]

In a study involving 8 type 1 diabetic subjects and 11 control subjects, the use of pramlintide acetate significantly reduced immediate postprandial hyperglycemia compared to just increasing insulin doses, indicating its efficacy in managing blood sugar levels after meals.

Pramlintide not only lowered post-meal blood sugar spikes but also suppressed glucagon levels, while glucagon injections helped prevent late postprandial hypoglycemia, suggesting a beneficial role for glucagon modulation in type 1 diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of amylin and glucagon in the dampening of glycemic excursions in children with type 1 diabetes. Heptulla, RA., Rodriguez, LM., Bomgaars, L., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

A fully artificial pancreas versus a hybrid artificial pancreas for type 1 diabetes: a single-centre, open-label, randomised controlled, crossover, non-inferiority trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pramlintide improved measures of glycemic control and body weight in patients with type 1 diabetes mellitus undergoing continuous subcutaneous insulin infusion therapy. [2022]

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

Pramlintide lowered glucose excursions and was well-tolerated in adolescents with type 1 diabetes: results from a randomized, single-blind, placebo-controlled, crossover study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Properties of pramlintide and insulin upon mixing. [2019]

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

A double-blind, placebo-controlled trial assessing pramlintide treatment in the setting of intensive insulin therapy in type 1 diabetes. [2022]

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

A co-formulation of pramlintide and insulin A21G (ADO09) improves postprandial glucose and short-term control of mean glucose, time in range, and body weight versus insulin aspart in adults with type 1 diabetes. [2023]

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

Efficacy and safety of pramlintide injection adjunct to insulin therapy in patients with type 1 diabetes mellitus: a systematic review and meta-analysis. [2019]

8. Canada pubmed.ncbi.nlm.nih.gov

Fully Automated Artificial Pancreas for Adults With Type 1 Diabetes Using Multiple Hormones: Exploratory Experiments. [2022]

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

The role of amylin and glucagon in the dampening of glycemic excursions in children with type 1 diabetes. [2019]