Automated Insulin + Pramlintide Delivery for Type 1 Diabetes

(FCL Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Michael Tsoukas, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

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

Prior Safety Data

Approved in 2 Jurisdictions

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}

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 am 18 years old or older.

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

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

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.

Trial 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 (Other)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Research Institute of the McGill University Health Center Montreal, Canada

Who Is Running the Clinical Trial?

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

Juvenile Diabetes Research Foundation Collaborator

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] For people with type 1 diabetes, there is currently no automated insulin delivery system that does not require meal input. We aimed to assess the efficacy of a novel faster-acting insulin aspart (Fiasp) plus pramlintide fully closed-loop system that does not require meal input.

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] To assess the safety and efficacy of the addition of pramlintide to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM).

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] To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of pramlintide in treating adolescents with type 1 diabetes.

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

Properties of pramlintide and insulin upon mixing. [2019] The pharmacokinetics, pharmacodynamics, and safety of pramlintide and various insulin formulations in patients with type 1 diabetes mellitus (DM) when given as separate injections or mixed in the same syringe before injection were studied.

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] To assess safety, efficacy, and tolerability of pramlintide dose escalation with proactive mealtime insulin reduction, followed by insulin optimization, in patients with type 1 diabetes.

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] Pramlintide improves postprandial glucose but requires additional injections. We investigated the pharmacokinetics/pharmacodynamics, efficacy and safety of ADO09, pramlintide/insulin A21G co-formulation, in type 1 diabetes (T1D).

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] We aim to assess the efficacy and safety of pramlintide plus insulin therapy in patients with type 1 diabetes.

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

Fully Automated Artificial Pancreas for Adults With Type 1 Diabetes Using Multiple Hormones: Exploratory Experiments. [2022] A fully automated insulin-pramlintide-glucagon artificial pancreas that alleviates the burden of carbohydrate counting without degrading glycemic control was iteratively enhanced until convergence through pilot experiments on adults with type 1 diabetes.

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] Postprandial hyperglycemia and preprandial hypoglycemia contribute to poor glycemic control in type 1 diabetes. We hypothesized that postprandial glycemic excursions could be normalized in type 1 diabetes by suppressing glucagon with pramlintide acetate in the immediate postprandial period and supplementing glucagon in the late postprandial period. A total of 11 control subjects were compared with 8 type 1 diabetic subjects on insulin pump therapy, using the usual insulin bolus-to-carbohydrate ratio during a standard liquid meal. Type 1 diabetic subjects were then randomized to two open-labeled studies. On one occasion, type 1 diabetic subjects received a 60% increase in the insulin bolus-to-carbohydrate ratio with minidose glucagon rescue injections, and on the other occasion type 1 diabetic subjects received 30-45 microg pramlintide with their usual insulin bolus-to-carbohydrate ratio. Glucose, glucagon, amylin (pramlintide), and insulin concentrations were measured for 420 min. The plasma glucose area under the curve (AUC) for 0-420 min was lower in control versus type 1 diabetic subjects (316 +/- 5 vs. 929 +/- 18 mg x h(-1) x dl(-1), P