Type 1 Diabetes
Conditions
Keywords
automated insulin delivery systems, glucose sensor, pramlintide
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.
Interventions
DEVICEMPC closed-loop system in insulin only mode
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.
DEVICEMPC closed-loop system in insulin/pramlintide mode
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 both insulin and pramlintide continuously for managing blood sugar. The system will deliver pramlintide in a fixed ratio to insulin at 6 mcg of pramlintide delivered for every 1 unit of insulin.
Sponsors
Oregon Health and Science University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incremental Area Under the Curve of Postprandial Glucose Following the First Meal | 6 hours following 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. |
| Percent of Time With Sensed Glucose Between 70 - 180 mg/dl Following First Meal | 6 hours 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incremental Area Under the Curve of Postprandial Glucose Following the Second Meal | 6 hours following second 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 iAUC/1000. |
| Percent of Time With Sensed Glucose Between 70 - 180 mg/dl Following Second Meal | 6 hours 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. |
| Net Area Under the Curve of Postprandial Glucose Following the First Meal | 6 hours following 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. |
| Net Area Under the Curve of Postprandial Glucose Following the Second Meal | 6 hours following second 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 |
| Net Area Under the Curve of Postprandial Glucose | 12 hour clinic visit | 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. |
| Percent of Time With Sensed Glucose <70 mg/dL Following First Meal | 6 hours 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 |
| Percent of Time With Sensed Glucose <70 mg/dL Following Second Meal | 6 hours 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 |
| Percent of Time With Sensed Glucose <70 mg/dL | 12 hour clinic visit | 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 |
| Percent of Time With Sensed Glucose Between 70-140 mg/dL Following First Meal | 6 hours 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. |
| Percent of Time With Sensed Glucose Between 70-140 mg/dL Following Second Meal | 6 hours 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. |
| Percent of Time With Sensed Glucose Between 70-140 mg/dL | 12 hour clinic visit | 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. |
| Mean Sensed Glucose Following First Meal | 6 hours 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. |
| Mean Sensed Glucose Following Second Meal | 6 hours 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. |
| Mean Sensed Glucose | 12 hour clinic visit | 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. |
| Percent of Time With Sensed Glucose <54 mg/dL Following First Meal | 6 hours 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 |
| Percent of Time With Sensed Glucose <54 mg/dL Following Second Meal | 6 hours 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 |
| Percent of Time With Sensed Glucose <54 mg/dL | 12 hour clinic visit | 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. |
| Percent of Time With Sensed Glucose >180 mg/dL Following First Meal | 6 hours 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. |
| Percent of Time With Sensed Glucose >180 mg/dL Following Second Meal | 6 hours 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. |
| Percent of Time With Sensed Glucose >180 mg/dL | 12 hour clinic visit | 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. |
| Percent of Time With Sensed Glucose >250 mg/dL Following First Meal | 6 hours 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. |
| Percent of Time With Sensed Glucose >250 mg/dL Following Second Meal | 6 hours 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. |
| Percent of Time With Sensed Glucose >250 mg/dL | 12 hour clinic visit | 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. |
| Median Amount of Insulin Delivered Following First Meal | 6 hours following the first meal | Amount of insulin (units) delivered in the 6 hours following the first meal. |
| Median Amount of Insulin Delivered Following Second Meal | 6 hours following the second meal | Amount of insulin (units) delivered. in the 6 hours following the second meal. |
| Median Amount of Insulin Delivered | 12 hour clinic visit | Amount of insulin (units) delivered |
| Median Amount of Pramlintide Delivered Following First Meal | 6 hours following the first meal | Amount of pramlintide (mcg) delivered in the 6 hours following the first meal. |
| Median Amount of Pramlintide Delivered Following Second Meal | 6 hours following the second meal | Amount of pramlintide (mcg) delivered in the 6 hours following the second meal. |
| Median Amount of Pramlintide Delivered | 12 hour clinic visit | Amount of pramlintide (mcg) delivered |
| Coefficient of Variation Following First Meal | 6 hours following the 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. |
| Coefficient of Variation Following Second Meal | 6 hours following the second 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. |
| Coefficient of Variation | 12 hour clinic visit | 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 twelve hours in the clinic. |
| Low Blood Glucose Index (LBGI) Following the First Meal | 6 hours 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 |
| Low Blood Glucose Index (LBGI) Following the Second Meal | 6 hours following the second 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 |
| Low Blood Glucose Index (LBGI) | 12 hour clinic visit | 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 |
| High Blood Glucose Index (HBGI) Following the First Meal | 6 hours 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 |
| High Blood Glucose Index (HBGI) Following the Second Meal | 6 hours following the second 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 |
| High Blood Glucose Index (HBGI) | 12 hour clinic visit | 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 |
| Adverse Events Related to Pramlintide | 4 days of pramlintide use | Assess the number of adverse events probably or possibly associated with pramlintide administration. |
| Baxter Retching Faces (BARF) Visual Analog Scale for Gastrointestinal Issues After the First Meal | 6 hours following 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). |
| Baxter Retching Faces (BARF) Visual Analog Scale for Gastrointestinal Issues After the Second Meal | 6 hours following second 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). |
| Mean Duration of Gastrointestinal Issues After the First Meal | 6 hours following 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. |
| Mean Duration of Gastrointestinal Issues After the Second Meal | 6 hours following 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. |
| Episodes of Hypoglycemia | 12 hour clinic visit | Counts of the number of episodes when the continuous glucose monitoring (CGM) values were \<70 mg/dL for 10 minutes or more. |
| Episodes of Carbohydrate Intake to Treat Hypoglycemia | 12 hour clinic visit | Assess the number of rescue carbohydrate treatments (defined as 15 grams of carbohydrate intake) needed to treat hypoglycemia. |
| Number of Provider-administered Insulin Injections | 12 hour clinic visit | Assess the number of provider-administered insulin injections due to hyperglycemia. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLeah Wilson, MD
Oregon Health and Science University
Participant flow
Recruitment details
A total of 35 people (19 females and 16 males) with type 1 diabetes mellitus have completed screening visits for the study from July-December 2024.
Pre-assignment details
Participants were randomized immediately after screening.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 34.8 Years STANDARD_DEVIATION 10.6 |
| Duration of diabetes | 17.2 years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Glucose at start of insulin-only arm | 121.2 mg/dl STANDARD_DEVIATION 33 |
| Glucose at start of pramlintide arm | 128.4 mg/dl STANDARD_DEVIATION 44.2 |
| Hemoglobin A1c | 7.6 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
| Weight in kg | 90.3 kg STANDARD_DEVIATION 14.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 31 |
| other Total, other adverse events | 17 / 31 | 0 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 |
Outcome results
None listed