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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new insulin delivery system for people with type 1 diabetes. It aims to determine if an automated system using Lyumjev insulin and pramlintide (a hormone that slows digestion) can better control blood sugar compared to current methods that require counting carbohydrates. Participants will try different setups of the Fully Automated Insulin and Pramlintide Delivery System or a system using insulin and a placebo. This trial suits those who have managed type 1 diabetes with an insulin pump for at least three months. As a Phase 2/3 trial, the study focuses on measuring the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to advancing diabetes care.

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.

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

Research shows that a fully automated system for delivering insulin and pramlintide safely manages type 1 diabetes. One study found that people using this system experienced fewer episodes of low blood sugar (hypoglycemia) than those using a partly automated system. Specifically, only 33% of participants reported low blood sugar with the fully automated system, compared to 58% with the partly automated one. This suggests that the fully automated system might be easier to use.

Automated insulin delivery systems, in general, have been shown to help people with type 1 diabetes maintain stable blood sugar levels. These systems can also lower HbA1c, a measure of average blood sugar over time, and improve overall health. Additionally, using a device that combines fast-acting insulin and pramlintide has been found to control blood sugar better than using fast-acting insulin alone.

These findings come from studies conducted before this trial, providing evidence that the treatment might be safe and well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the automated insulin and pramlintide delivery system for Type 1 diabetes because it offers a novel approach to managing blood sugar levels without meal announcements. Unlike standard insulin pumps and continuous glucose monitors that often require users to announce meals or manually input carbohydrate counts, this system automates insulin and pramlintide delivery, potentially reducing the burden on users. The fully automated system has two variations: one with a ratio of 1 unit of insulin for 10 μg of pramlintide and another with 1 unit for 8 μg. This integration of pramlintide, an amylin analog that slows gastric emptying and suppresses glucagon secretion, adds an extra layer of blood sugar control that current insulin-only systems do not provide.

What evidence suggests that this trial's treatments could be effective for type 1 diabetes?

Research shows that a fully automated system for delivering insulin and pramlintide, which participants in this trial may receive, helps people with type 1 diabetes better control their blood sugar. Studies have found that this system keeps blood sugar levels in a healthy range for longer periods. One study discovered that using insulin and pramlintide together in this automated system reduces the need to count carbohydrates, making diabetes management easier without losing control over blood sugar levels. Early results also suggest that the system can be adjusted to find the right balance of insulin and pramlintide for each person. Overall, this approach using two hormones appears promising for making diabetes care more effective and less burdensome. ^{2 5 6 7 8}

Who Is on the Research Team?

Michael Tsoukas, M.D.

Principal Investigator

Research Institute of the McGill University Health Center

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

Michael Vallis, Ph.D.

Principal Investigator

Dalhousie University Psychologist

Natasha Garfield, M.D.

Principal Investigator

Royal Victoria Hospital Division of Endocrinology

Melissa-Rosina Pasqua, M.D.

Principal Investigator

Research Institute of the McGill University Health Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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 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]

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]

Citations

1. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/434416

A Fully Automated Lyumjev and Pramlintide Delivery System ... The aim of this clinical trial is to investigate whether a fully automated Lyumjev-and-pramlintide delivery system improves glycemic ...

2. withpower.com withpower.com/trial/phase-2-and-3-diabetes-mellitus-9-2023-a9c7d

Automated Insulin + Pramlintide Delivery for Type 1 Diabetes The aim of this clinical trial is to investigate whether a fully automated Lyumjev-and-pramlintide delivery system improves glycemic outcomes in adults with ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41174925/?utm_source=FeedFetcher&utm_medium=rss&utm_campaign=None&utm_content=0LAB9c0crr3A83hH-HGUC1eKWrPWmTpzj_4qs7g2IoX&fc=None&ff=20251101191909&v=2.18.0.post22+67771e2

A Pilot Outpatient Assessment of a Fully Closed-Loop ... This study suggests that automated insulin and pramlintide systems have the potential to alleviate carbohydrate counting without degrading ...

4. thelancet.com thelancet.com/journals/landig/article/PIIS2589-7500(24)00092-X/fulltext

Simple meal announcements and pramlintide delivery ... With the insulin-and-pramlintide system with simple meal announcements, 14 (47%) participants reported mild gastrointestinal symptoms and two (7%) reported ...

5. diabetesjournals.org diabetesjournals.org/care/article/43/3/597/35620/A-Novel-Dual-Hormone-Insulin-and-Pramlintide

A Novel Dual-Hormone Insulin-and-Pramlintide Artificial ... In this study, we compared two novel insulin-and-pramlintide artificial pancreas systems with rapid insulin-alone artificial pancreas. The rapid ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04243629

Co-administration of Pramlintide and Insulin Via an ... The aim of this project is to assess whether co-administration of pramlintide with rapid insulin in an artificial pancreas system will improve glycemic control ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12213545/

Research Gaps, Challenges, and Opportunities in ... Automated insulin delivery (AID) systems have enabled people living with T1D to safely manage their glucose, reduce their HbA1c, and improve their overall ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1530891X25009243

The Future of Automated Insulin Delivery Systems This review examines key limitations of current AID systems and explores future directions, including fully closed-loop control, novel insulin formulations, ...