Two Way Crossover Closed Loop Study Insulin vs Insulin and Pramlintide

Oregon Health and Science University33 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

MPC closed-loop system in insulin only modeDEVICE

The Model Predictive Control (MPC) insulin infusion algorithm contains a model within the controller that takes as an input the aerobic metabolic expenditure in addition to the CGM and meal in puts. The algorithm uses heart rate and accelerometer data collected on the patient's body to calculate metabolic expenditure (METs). The METs then acts on the model for the insulin dynamics, whereby more energy expenditure and longer duration exercise can lead to a more substantial effect of insulin on the CGM. The MPC also has missed meal insulin bolus detection where the system will calculate the amount of insulin that was missed for a meal. The missed meal boluses can be delivered automatically without any input from the user. This feature can also be disabled. The device in this mode will administer insulin continuously for managing blood sugar.

MPC closed-loop system in insulin/pramlintide modeDEVICE

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Incremental Area Under the Curve of Postprandial Glucose Following the First Meal

Incremental area under the curve (iAUC) of postprandial glucose (mg/dL\*min) calculated using a trapezoidal method, which sums all continuous glucose monitoring (CGM) values above the starting glucose for the obseration period. Values shown are (mg/dL\*min)/1000.

Time frame: 6 hours following first meal

Percent of Time With Sensed Glucose Between 70 - 180 mg/dl Following First Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. Percent of time in range can take values between 0 and 100 and uses the six hours following the meal as the denominator.

Time frame: 6 hours following first meal

Secondary Outcomes

Incremental Area Under the Curve of Postprandial Glucose Following the Second Meal

Time frame: 6 hours following second meal

Percent of Time With Sensed Glucose Between 70 - 180 mg/dl Following Second Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. Percent of time in range can take values between 0 and 100 and uses the six hours following the meal as the denominator.

Time frame: 6 hours following second meal

Net Area Under the Curve of Postprandial Glucose Following the First Meal

Net area under the curve (netAUC) of postprandial glucose (mg/dL\*min) calculated using a trapezoidal method, which sums all continuous glucose monitoring (CGM) values above the starting glucose and subtracts CGM values below the starting glucose for the observation period. Values shown are (mg/dL\*min)/1000.

Time frame: 6 hours following first meal

Net Area Under the Curve of Postprandial Glucose Following the Second Meal

Time frame: 6 hours following second meal

Net Area Under the Curve of Postprandial Glucose

Time frame: 12 hour clinic visit

Percent of Time With Sensed Glucose <70 mg/dL Following First Meal

Assess the percent of time that the Dexcom G6 reported sensor glucose values less than 70 mg/dl using Dexcom sensor in the 6 hours following the start of the first meal. Because so few participants had any sensed glucose values \<70 mg/dL, this summary shows the count of participants with any time (\>0) with sensed glucose \<70 mg/dL

Time frame: 6 hours following first meal

Percent of Time With Sensed Glucose <70 mg/dL Following Second Meal

Because so few participants had any sensed glucose values \<70 mg/dL, this summary shows the count of participants with any time (\>0) with sensed glucose \<70 mg/dL

Time frame: 6 hours following second meal

Percent of Time With Sensed Glucose <70 mg/dL

Because so few participants had any sensed glucose values \<70 mg/dL, this summary shows the count of participants with any time (\>0) with sensed glucose \<70 mg/dL

Time frame: 12 hour clinic visit

Percent of Time With Sensed Glucose Between 70-140 mg/dL Following First Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. Percent of time in range can take values between 0 and 100 and uses the six hours following the meal as the denominator.

Time frame: 6 hours following first meal

Percent of Time With Sensed Glucose Between 70-140 mg/dL Following Second Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. Percent of time in range can take values between 0 and 100 and uses the six hours following the meal as the denominator.

Time frame: 6 hours following second meal

Percent of Time With Sensed Glucose Between 70-140 mg/dL

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. Percent of time in range can take values between 0 and 100 and uses the twelve hours of the clinic visit as the denominator.

Time frame: 12 hour clinic visit

Mean Sensed Glucose Following First Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. The outcome is calculated as the average of these values for the six hours following the meal.

Time frame: 6 hours following first meal

Mean Sensed Glucose Following Second Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. The outcome is calculated as the average of these values for the six hours following the meal.

Time frame: 6 hours following second meal

Mean Sensed Glucose

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. The outcome is calculated as the average of these values for the twelve-hour clinic visit.

Time frame: 12 hour clinic visit

Percent of Time With Sensed Glucose <54 mg/dL Following First Meal

Because so few participants had any sensed glucose values \<54 mg/dL, this summary shows the count of participants with any time (\>0) with sensed glucose \<54 mg/dL

Time frame: 6 hours following first meal

Percent of Time With Sensed Glucose <54 mg/dL Following Second Meal

Because so few participants had any sensed glucose values \<54 mg/dL, this summary shows the count of participants with any time (\>0) with sensed glucose \<54 mg/dL

Time frame: 6 hours following second meal

Percent of Time With Sensed Glucose <54 mg/dL

Because so few participants had any sensed glucose values \<54 mg/dL, this summary shows the count of participants with any time (\>0) with sensed glucose \<54 mg/dL.

Time frame: 12 hour clinic visit

Percent of Time With Sensed Glucose >180 mg/dL Following First Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. Percent of time in range can take values between 0 and 100 and uses the six hours following the meal as the denominator.

Time frame: 6 hours following first meal

Percent of Time With Sensed Glucose >180 mg/dL Following Second Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. Percent of time in range can take values between 0 and 100 and uses the six hours following the meal as the denominator.

Time frame: 6 hours following second meal

Percent of Time With Sensed Glucose >180 mg/dL

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. Percent of time in range can take values between 0 and 100 and uses the twelve-hour clinic visit as the denominator.

Time frame: 12 hour clinic visit

Percent of Time With Sensed Glucose >250 mg/dL Following First Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. Percent of time in range can take values between 0 and 100 and uses the six hours after the meal as the denominator.

Time frame: 6 hours following first meal

Percent of Time With Sensed Glucose >250 mg/dL Following Second Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. Percent of time in range can take values between 0 and 100 and uses the six hours after the meal as the denominator.

Time frame: 6 hours following second meal

Percent of Time With Sensed Glucose >250 mg/dL

Time frame: 12 hour clinic visit

Median Amount of Insulin Delivered Following First Meal

Amount of insulin (units) delivered in the 6 hours following the first meal.

Time frame: 6 hours following the first meal

Median Amount of Insulin Delivered Following Second Meal

Amount of insulin (units) delivered. in the 6 hours following the second meal.

Time frame: 6 hours following the second meal

Median Amount of Insulin Delivered

Amount of insulin (units) delivered

Time frame: 12 hour clinic visit

Median Amount of Pramlintide Delivered Following First Meal

Amount of pramlintide (mcg) delivered in the 6 hours following the first meal.

Time frame: 6 hours following the first meal

Median Amount of Pramlintide Delivered Following Second Meal

Amount of pramlintide (mcg) delivered in the 6 hours following the second meal.

Time frame: 6 hours following the second meal

Median Amount of Pramlintide Delivered

Amount of pramlintide (mcg) delivered

Time frame: 12 hour clinic visit

Coefficient of Variation Following First Meal

Blood glucose values are recorded every 5 minutes using the Dexcom G6 sensor. The coefficient of variation outcome is calculated as (100 \* \[standard deviation\] / mean) of these values for the six hours following the meal.

Time frame: 6 hours following the first meal

Coefficient of Variation Following Second Meal

Time frame: 6 hours following the second meal

Coefficient of Variation

Time frame: 12 hour clinic visit

Low Blood Glucose Index (LBGI) Following the First Meal

The Low Blood Glucose Index (LBGI) was calculated and categorized following accepted methods as described in: Clarke W, Kovatchev B. Statistical tools to analyze continuous glucose monitor data. Diabetes Technol Ther. 2009;11(Suppl 1):S-45-S-54. doi:10.1089/dia.2008.0138

Time frame: 6 hours following the first meal

Low Blood Glucose Index (LBGI) Following the Second Meal

Time frame: 6 hours following the second meal

Low Blood Glucose Index (LBGI)

Time frame: 12 hour clinic visit

High Blood Glucose Index (HBGI) Following the First Meal

The High Blood Glucose Index (HBGI) was calculated and categorized following accepted methods as described in: Clarke W, Kovatchev B. Statistical tools to analyze continuous glucose monitor data. Diabetes Technol Ther. 2009;11(Suppl 1):S-45-S-54. doi:10.1089/dia.2008.0138

Time frame: 6 hours following the first meal

High Blood Glucose Index (HBGI) Following the Second Meal

Time frame: 6 hours following the second meal

High Blood Glucose Index (HBGI)

Time frame: 12 hour clinic visit

Adverse Events Related to Pramlintide

Assess the number of adverse events probably or possibly associated with pramlintide administration.

Time frame: 4 days of pramlintide use

Baxter Retching Faces (BARF) Visual Analog Scale for Gastrointestinal Issues After the First Meal

Six hours after the meal, participants were asked to use the Baxter Retching Faces (BARF) visual analog scale to indicate the worst nausea/vomiting discomfort they felt over the prior 6 hours. The scale ranges from 0 (none) to 10 (most discomfort).

Time frame: 6 hours following first meal

Baxter Retching Faces (BARF) Visual Analog Scale for Gastrointestinal Issues After the Second Meal

Time frame: 6 hours following second meal

Mean Duration of Gastrointestinal Issues After the First Meal

Six hours after the meal, participants were asked to report the approximate number of minutes they felt nausea during the prior 6 hours.

Time frame: 6 hours following first meal

Mean Duration of Gastrointestinal Issues After the Second Meal

Six hours after the meal, participants were asked to report the approximate number of minutes they felt nausea during the prior 6 hours.

Time frame: 6 hours following second meal

Episodes of Hypoglycemia

Counts of the number of episodes when the continuous glucose monitoring (CGM) values were \<70 mg/dL for 10 minutes or more.

Time frame: 12 hour clinic visit

Episodes of Carbohydrate Intake to Treat Hypoglycemia

Assess the number of rescue carbohydrate treatments (defined as 15 grams of carbohydrate intake) needed to treat hypoglycemia.

Time frame: 12 hour clinic visit

Number of Provider-administered Insulin Injections

Assess the number of provider-administered insulin injections due to hyperglycemia.

Time frame: 12 hour clinic visit

Two Way Crossover Closed Loop Study Insulin vs Insulin and Pramlintide

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes