Clinical trial NCT06046417: A Fully Automated Lyumjev and Pramlintide Delivery System for Adults With Type 1 Diabetes
Official title: A Randomized, Controlled, Crossover Trial to Assess a Fully Automated, Dual-hormone (Insulin-and-pramlintide) Delivery System Without Carbohydrate Counting in Regulating Glucose Levels in Adults With Type 1 Diabetes.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: type1diabetes
Diabetes Mellitus, Type 1
Keywords: Pramlintide
fully automated delivery system
artificial pancreas
Insulin
Lyumjev
fully closed loop
adjunctive
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2023-09-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The aim of this study is to conduct an outpatient, randomized, crossover clinical trial to compare the glycemic outcomes of a fully automated Lyumjev-pramlintide delivery system to a hybrid automated Lyumjev-placebo delivery system with carbohydrate counting in 26 adults with type 1 diabetes.

Design-

All participants will undergo three interventions in a random order:

(i) Fully automated Lyumjev insulin-pramlintide delivery system. Ratio of 1 unit of inulin for 8μg of pramlintide.

(ii) Fully automated Lyumjev insulin-pramlintide delivery system. Ratio of 1 unit of insulin for 10μg of pramlintide.

(iii) Hybrid automated Lyumjev insulin-placebo delivery system with carbohydrate-matched boluses.

Study drugs-

Lyumjev is a Health Canada insulin for treatment of type 1 diabetes. Participants who do not currently use Lyumjev will be switched to it for the duration of the study.

Pramlintide is an FDA-approved drug used in the treatment of type 1 diabetes. It contributes to regulating glucose levels by delaying gastric emptying, suppressing nutrient-stimulated glucagon secretion and increasing satiety. It is not approved for commercial use by Health Canada, but has been approved for the purpose of the study.

Study Devices-

For the duration of the study, participants will use a Dexcom G6 Continuous Glucose Monitor (GCM), two YpsoPumps (for insulin and pramlintide) as well as a study smartphone with the Euglide application installed. The automated insulin delivery (AID) system will integrate these sets of devices to automate insulin (and pramlintide) delivery in response to an individual's glucose levels.

Treatment Period-

Each intervention will last three weeks and be preceded by a 5-day at-home run-in period. After both the second and third interventions, there will be a 14-45 day washout period. Participants will be followed-up with remotely on days 2 (+/-1) and 5 of each run-in and on days 2(+/-1), 3(+/-1) and 7(+/-2) of each intervention. Remote contact can be performed via phone, email, text message or another reasonable communication channel. After each intervention, participants will be interviewed and asked to complete questionnaires assessing diabetes control and quality of life. Participants will need approximately 15-30 weeks to complete the study.

The study will enroll up to 4 pilot participants, as well as 26 main study participants who meet the eligibility criteria.

Eligibility criteria: Inclusion Criteria:

* Individuals ≥ 18 years of age.
* A clinical diagnosis of type 1 diabetes for at least 12 months. The diagnosis of type 1 diabetes relies on the investigator's judgment; C peptide level and antibody determinations are unnecessary.
* Using insulin pump therapy for at least three months.
* 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:

* Current or recent use of antihyperglycemic agents other than insulin (≤ 2-week use of sodium-glucose cotransporter-2 inhibitor (SGLT2I), Metformin, etc.; ≤ 1-month for glucagon-like peptide-1 receptor agonists (GLP1-RA)).
* Current use of glucocorticoid medication (except low, stable doses and inhaled steroids).
* Individuals with confirmed gastroparesis.
* Use of medication that alters gastrointestinal motility (ex: domperidone).
* Use of hydroxyurea.
* Planned or ongoing pregnancy.
* Breastfeeding individuals.
* Severe hypoglycemia requiring hospitalization in the past month. Severe hypoglycemia is defined as requiring the assistance of another person, due to altered consciousness, to administer carbohydrates, glucagon, or other resuscitative actions.
* Diabetic ketoacidosis episode in the past month.
* Clinically significant nephropathy, neuropathy, or retinopathy as judged by the investigator.
* Recent (\< 6 months) acute macrovascular event, e.g., acute coronary syndrome.
* Other serious medical illnesses which are likely to interfere with study participation or the ability to complete the trial by the investigator's judgment.
* Known hypersensitivity to the study drugs or their excipients.

Primary outcomes:
measure: Percentage of time of glucose levels spent in the target range (3.9-10.0 mmol/L).
timeFrame: 18 days
Secondary outcomes:
measure: Percentage of time of glucose levels spent between 3.9-7.8 mmol/L.
timeFrame: 18 days
measure: Percentage of time of glucose levels spent between 3.0-3.9 mmol/L.
timeFrame: 18 days
measure: Percentage of time of glucose levels spent between 10.0-13.9 mmol/L.
timeFrame: 18 days
measure: Mean glucose levels.
timeFrame: 18 days
measure: Standard deviation of glucose levels.
timeFrame: 18 days
measure: Coefficient of variance of glucose levels.
timeFrame: 18 days
measure: Total pramlintide delivery (overall, basal, and bolus).
timeFrame: 18 days
measure: Total insulin delivery (overall, basal, and bolus).
timeFrame: 18 days
measure: Mean score on the Type 1 Diabetes Distress Scale (T1DDS) excluding the physician subscale.
timeFrame: 18 days
measure: Mean score on the Hypoglycemia Fear Survey - II (Worry Subscale) (HSF2).
timeFrame: 18 days
measure: Mean score on the INSPIRE questionnaire for adults (INSPIRE).
timeFrame: 18 days
measure: Mean score on selected items from The Diabetes Bowel Symptoms Questionnaire (DBSQ).
timeFrame: 18 days
measure: Mean score on a Treatment Satisfaction Questionnaire (TSQ) taken from Marrero et al.
timeFrame: 18 days
measure: Thematic interview analysis
timeFrame: 18 days
Other outcomes:
measure: Safety Endpoints
timeFrame: 18 days
Locations:
city: Montreal
country: Canada
facility: Research Institute of the McGill University Health Center
state: Quebec
Study officials:
affiliation: Research Institute of the McGill University Health Center
name: Michael Tsoukas, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Research Institute of the McGill University Health Center
name: Ahmad Haidar, Ph.D.
role: STUDY_CHAIR
affiliation: Montreal's Children's Hospital Division of Endocrinology
name: Laurent Legault, M.D.
role: STUDY_CHAIR
affiliation: Dalhousie University Psychologist
name: Michael Vallis, Ph.D.
role: STUDY_CHAIR
affiliation: Royal Victoria Hospital Division of Endocrinology
name: Natasha Garfield, M.D.
role: STUDY_CHAIR
affiliation: Research Institute of the McGill University Health Center
name: Melissa-Rosina Pasqua, M.D.
role: STUDY_CHAIR
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