Clinical trial NCT06422325: Two Way Crossover Closed Loop Study Insulin vs Insulin and Pramlintide
Official title: A Crossover Study to Evaluate Insulin/Pramlintide Versus Insulin Alone Delivery Strategy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: automated insulin delivery systems
glucose sensor
pramlintide
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2024-05-20
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test how well a new investigational closed loop system manages your blood sugar with the ability to deliver insulin and pramlintide. Pramlintide is a drug that is used with mealtime insulin to control blood sugar in people who have diabetes. It works by slowing down the movement of food through the stomach which prevents blood sugar from rising too high after a meal. The closed loop system will receive glucose values from the Dexcom G6 continuous glucose monitoring (CGM) and automatically send commands to one Omnipod for insulin and one Omnipod for pramlintide delivery.

Detailed description: Participants will undergo two 12.5 hour clinic visits. Participants will complete a training on how to start the Dexcom G6 sensor at home. Participants will start the G6 sensor the day before each study visit. For one visit, the system will use insulin only for managing blood sugar. For the other study, the system will use both insulin and pramlintide. The order of the visits will be randomly chosen. For 3 days before the insulin and pramlintide visit, participants will dose with pramlintide before each meal. During the visits, participants will wear one or two Omnipods to delivery insulin and insulin/pramlintide and a Dexcom G6 CGM. The CGM system will provide sensor glucose data every 5 minutes. Sensor glucose data will be wirelessly transmitted via Bluetooth Low Energy (BTLE) from the Dexcom G6 to the smartphone master controller every 5 minutes. The smartphone will communicate via BTLE to an Omnipod for insulin delivery. The closed loop system will receive activity data through a Polar M600 watch worn by the participant. Participants will eat breakfast and lunch in clinic.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of type 1 diabetes mellitus for at least 1 year.
* Participants 18 to 70 years of age.
* Current use of an insulin pump for at least 3 months with stable insulin pump settings for \>2 weeks OR current use of multiple day injection insulin therapy with stable doses for \>2 weeks.
* Uses a carbohydrate ratio, at lease occasionally, to dose meal time insulin.
* HbA1c ≤ 10.5% at screening.
* Total daily insulin requirement is less than 139 units/day.
* Willingness to follow all study procedures, including attending all clinic visits.
* Willingness to sign informed consent and HIPAA documents.

Exclusion Criteria:

* Individual of childbearing potential who is pregnant or intending to become pregnant or breast-feeding, or is not using adequate contraceptive methods. Acceptable contraception includes birth control pill / patch / vaginal ring, Depo-Provera, Norplant, an IUD, the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
* Any cardiovascular disease, defined as a clinically significant EKG abnormality at the time of screening or any history of: stroke, heart failure, myocardial infarction, angina pectoris, or coronary arterial bypass graft or angioplasty. Diagnosis of 2nd or 3rd degree heart block or any non-physiological arrhythmia judged by the investigator to be exclusionary.
* Renal insufficiency (GFR \< 60 ml/min, using the MDRD equation as reported by the OHSU laboratory).
* Liver failure, cirrhosis, or any other liver disease that compromises liver function as determined by the investigator.
* History of severe hypoglycemia during the past 3 months prior to screening visit or hypoglycemia unawareness as judged by the investigator. Participants will complete a hypoglycemia awareness questionnaire. Participants will be excluded for four or more R responses.
* History of diabetes ketoacidosis during the prior 3 months prior to screening visit, as diagnosed on hospital admission or as judged by the investigator.
* Adrenal insufficiency.
* Any active infection requiring treatment (example soft tissue infection requiring antibiotics).
* Known or suspected abuse of alcohol, narcotics, or illicit drugs.
* Seizure disorder.
* Active foot ulceration.
* Major surgical operation within 30 days prior to screening.
* Use of an investigational drug within 30 days prior to screening.
* Chronic usage of any immunosuppressive medication (such as cyclosporine, azathioprine, sirolimus, or tacrolimus).
* Bleeding disorder, treatment with warfarin, or platelet count below 50,000.
* Allergy to aspart insulin.
* Allergy to pramlintide.
* Current administration of oral or parenteral corticosteroids.
* Any life-threatening disease, including malignant neoplasms and medical history of malignant neoplasms within the past 5 years prior to screening (except basal and squamous cell skin cancer).
* Current use of any medication intended to lower glucose other than insulin or pramlintide (ex. use of liraglutide, metformin).
* Gastroparesis
* Diets consisting of less than 50 grams of carbohydrates per day.
* Dietary restrictions or allergies to the study meals
* Any clinically significant disease or disorder which in the opinion of the Investigator may jeopardize the participant's safety or compliance with the protocol.

Primary outcomes:
measure: Incremental area under the curve of postprandial glucose following the first meal
timeFrame: 6 hours following first meal
measure: Percent of time with sensed glucose between 70 - 180 mg/dl following first meal
timeFrame: 6 hours following first meal
Secondary outcomes:
measure: Incremental area under the curve of postprandial glucose following the second meal
timeFrame: 6 hours following second meal
measure: Percent of time with sensed glucose between 70 - 180 mg/dl following second meal
timeFrame: 6 hours following second meal
measure: Net area under the curve of postprandial glucose following the first meal
timeFrame: 6 hours following first meal
measure: Net area under the curve of postprandial glucose following the second meal
timeFrame: 6 hours following second meal
measure: Net area under the curve of postprandial glucose
timeFrame: 12 hour clinic visit
measure: Percent of time with sensed glucose <70 mg/dL following first meal
timeFrame: 6 hours following first meal
measure: Percent of time with sensed glucose <70 mg/dL following second meal
timeFrame: 6 hours following second meal
measure: Percent of time with sensed glucose <70 mg/dL
timeFrame: 12 hour clinic visit
measure: Percent of time with sensed glucose between 70-140 mg/dL following first meal
timeFrame: 6 hours following first meal
measure: Percent of time with sensed glucose between 70-140 mg/dL following second meal
timeFrame: 6 hours following second meal
measure: Percent of time with sensed glucose between 70-140 mg/dL
timeFrame: 12 hour clinic visit
measure: Mean sensed glucose following first meal
timeFrame: 6 hours following first meal
measure: Mean sensed glucose following second meal
timeFrame: 6 hours following second meal
measure: Mean sensed glucose
timeFrame: 12 hour clinic visit
measure: Percent of time with sensed glucose <54 mg/dL following first meal
timeFrame: 6 hours following first meal
measure: Percent of time with sensed glucose <54 mg/dL following second meal
timeFrame: 6 hours following second meal
measure: Percent of time with sensed glucose <54 mg/dL
timeFrame: 12 hour clinic visit
measure: Percent of time with sensed glucose >180 mg/dL following first meal
timeFrame: 6 hours following first meal
measure: Percent of time with sensed glucose >180 mg/dL following second meal
timeFrame: 6 hours following second meal
measure: Percent of time with sensed glucose >180 mg/dL
timeFrame: 12 hour clinic visit
measure: Percent of time with sensed glucose >250 mg/dL following first meal
timeFrame: 6 hours following first meal
measure: Percent of time with sensed glucose >250 mg/dL following second meal
timeFrame: 6 hours following second meal
measure: Percent of time with sensed glucose >250 mg/dL
timeFrame: 12 hour clinic visit
measure: Mean amount of insulin delivered following first meal
timeFrame: 6 hours following the first meal
measure: Mean amount of insulin delivered following second meal
timeFrame: 6 hours following the second meal
measure: Mean amount of insulin delivered
timeFrame: 12 hour clinic visit
measure: Mean amount of pramlintide delivered following first meal
timeFrame: 6 hours following the first meal
measure: Mean amount of pramlintide delivered following second meal
timeFrame: 6 hours following the second meal
measure: Mean amount of pramlintide delivered
timeFrame: 12 hour clinic visit
measure: Coefficient of variation following first meal
timeFrame: 6 hours following the first meal
measure: Coefficient of variation following second meal
timeFrame: 6 hours following the second meal
measure: Coefficient of variation
timeFrame: 12 hour clinic visit
measure: Low Blood Glucose Index (LBGI) following the first meal
timeFrame: 6 hours following the first meal
measure: Low Blood Glucose Index (LBGI) following the second meal
timeFrame: 6 hours following the second meal
measure: Low Blood Glucose Index (LBGI)
timeFrame: 12 hour clinic visit
measure: High Blood Glucose Index (HBGI) following the first meal
timeFrame: 6 hours following the first meal
measure: High Blood Glucose Index (HBGI) following the second meal
timeFrame: 6 hours following the second meal
measure: High Blood Glucose Index (HBGI)
timeFrame: 12 hour clinic visit
measure: Adverse events related to pramlintide
timeFrame: 4 days of pramlintide use
measure: Baxter Retching Faces (BARF)/VAS scale for gastrointestinal issues after the first meal
timeFrame: 6 hours following first meal
measure: Baxter Retching Faces (BARF)/VAS scale for gastrointestinal issues after the second meal
timeFrame: 6 hours following second meal
measure: Mean duration of gastrointestinal issues after the first meal
timeFrame: 6 hours following first meal
measure: Mean duration of gastrointestinal issues after the second meal
timeFrame: 6 hours following second meal
measure: Episodes of carbohydrate intake to treat hypoglycemia
timeFrame: 12 hour clinic visit
measure: Episodes of hypoglycemia
timeFrame: 12 hour clinic visit
measure: Number of provider-administered insulin injections
timeFrame: 12 hour clinic visit
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Leah Wilson, MD
role: PRINCIPAL_INVESTIGATOR
References: