Two Way Crossover Closed Loop Study R-AP vs MPC

A Crossover Study to Assess the Efficacy of a Robust AP Closed Loop System vs MPC Closed Loop System

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05083559

Enrollment

Registered

2021-10-19

Start date

2021-12-08

Completion date

2022-03-03

Last updated

2023-01-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 1 Diabetes

Keywords

glucose sensor, automated insulin delivery systems

Brief summary

An artificial pancreas (AP) is a control system for automatic insulin delivery. The investigators have implemented a missed meal bolus detection algorithm for use within an AP control system. The robust R-AP system used in this protocol has been designed to handle a variety of real-world scenarios that are critical to a high-risk patient population. The investigators will test how well the new algorithm handles missed or inaccurate meal announcements. This type of algorithm may significantly improve glucose control over the standard model predictive control (MPC) closed-loop algorithm without these new algorithm features for patients with type 1 diabetes.

Detailed description

Participants will undergo two visits at Oregon Health and Science University (OHSU) that will evaluate missed meal bolus detection. Participants will arrive at approximately 7am for all visits, be monitored through the afternoon and discharged before dinner. During each of these intervention visits, participants will wear an Omnipod to deliver insulin and a Dexcom G6 Continuous Glucose Monitoring System (CGM) to measure glucose. The closed loop system will receive activity data through a Polar M600 watch worn by the participant. The studies will test the ability of the system to adapt to a missed meal bolus. Participants will eat self selected meals at 10 am and 2pm, both meals with a missed bolus, and these meals will be repeated across both study arms. For one missed meal bolus study, glucose will be controlled using the Robust R-AP closed-loop mode. During the other missed meal bolus study, glucose will be controlled using the MPC closed-loop mode. Participants will complete frequent glucose and ketone checks for safety.

Interventions

DEVICEMPC AP algorithm

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 inputs. The algorithm uses heart rate and accelerometer data collected on the patient's body to calculate metabolic expenditure. The metabolic expenditure 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.

DEVICERobust R-AP algorithm

The R-AP is a modified MPC algorithm. A new feature in the algorithm includes a model for missed meal insulin detection. The model includes estimations for carbohydrate consumption based glucose patterns to determine if that person has consumed a meal without announcing it to the system.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Diagnosis of type 1 diabetes mellitus for at least 1 year. * Male or female participants 18 to 65 years of age. * Current use of an insulin pump for at least 3 months with stable insulin pump settings for \>2 weeks. * 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

* Female 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 intra-uterine device (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 Modification of Diet in Renal Disease (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. * Hematocrit of less than 36% for men, less than 32% for women. * History of severe hypoglycemia during the past 12 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 6 months prior to screening visit, as diagnosed on hospital admission or as judged by the investigator. * Adrenal insufficiency. * Any active infection. * Known or suspected abuse of alcohol, narcotics, or illicit drugs. * Seizure disorder. * Active foot ulceration. * Severe peripheral arterial disease characterized by ischemic rest pain or severe claudication. * 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. * 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). * Beta blockers or non-dihydropyridine calcium channel blockers. * Current use of any medication intended to lower glucose other than insulin (ex. use of liraglutide). * Gastroparesis * 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
Area Under the Curve (AUC) of Postprandial Glucose	4 hour period following the first meal	Incremental AUC of postprandial glucose in the 4 hours following the start of first meal. AUC (mg/dL\*hr) will be calculated using a trapezoidal method, which sums all CGM values taken every 5 minutes in the 4 hour period following the meal above the starting glucose. This yields a maximum of 48 data points for the calculation.
Percent of Time With Sensed Glucose Between 70-180 mg/dl	4 hour period following the first meal	Assess the percent of time that the Dexcom G6 reported sensor glucose values between 70-180 mg/dl using Dexcom sensor for the four hour period following the first meal.

Secondary

Measure	Time frame	Description
Number of Provider-administered Insulin Injections	4 hour period following the first meal	Assess the cumulative number of provider-administered insulin injections to treat hyperglycemia in the 4 hour period following the first meal.
Mean Sensed Glucose	4 hour period following the first meal	Assess the mean sensed glucose from the Dexcom G6 reported sensor glucose values for the four hour period following the first meal.
Percent of Time With Sensed Glucose <54 mg/dl	4 hour period following the first meal	Assess the percent of time that the Dexcom G6 reported sensor glucose values less than 54 mg/dl using Dexcom sensor for the four hour period following the first meal.
Percent of Time With Sensed Glucose <70 mg/dl	4 hour period following the first meal	Assess the percent of time that the Dexcom G6 reported sensor glucose values less than 70 mg/dl using Dexcom sensor for the 4 hour period following the first meal.
Percent of Time With Sensed Glucose >250 mg/dl	4 hour period following the first meal	Assess the percent of time that the Dexcom G6 reported sensor glucose values greater than 250 mg/dl using Dexcom sensor for the four hour period following the first meal.
Mean Amount of Insulin Delivered Per Day (in Units)	4 hour period following the first meal	Assess the mean amount of insulin delivered per day by the Omnipod through the AP system study in units for the four hour period following the first meal.
Percent of Time With Sensed Glucose >180 mg/dl	4 hour period following the first meal	Assess the percent of time that the Dexcom G6 reported sensor glucose values greater than 180 mg/dl using Dexcom sensor for the four hour period following the first meal.
Number of Carbohydrate Treatments	4 hour period following the first meal	Assess the cumulative number of carbohydrate treatments (defined as 15 or 20 grams of carbohydrate) for the four hour period following the first meal.

Countries

United States

Participant flow

Participants by arm

Arm	Count
MPC to R-AP The randomization order for participants in this arm was Model Predictive Control (MPC) followed by Robust-Artificial Pancreas (R-AP). Each visit was about 72 hours and included a 12 hour inpatient and 60 hour outpatient portion.	7
R-AP to MPC The randomization order for participants in this arm was Robust-Artificial Pancreas (R-AP followed by Model Predictive Control (MPC). Each visit was about 72 hours and included a 12 hour inpatient and 60 hour outpatient portion.	8
Total	15

Withdrawals & dropouts

Period	Reason	FG000	FG001
First Intervention (~8 Hours)	hit stopping rules for hyperglycemia	4	1
Second at Home Period (3-30 Days)	Withdrawal by Subject	2	0
Second Intervention Visit (~8 Hours)	hit stopping rules for hyperglycemia	1	0

Baseline characteristics

Characteristic	MPC to R-AP	R-AP to MPC	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	7 Participants	8 Participants	15 Participants
Age, Continuous	41.6 years STANDARD_DEVIATION 10.1	34.1 years STANDARD_DEVIATION 9.9	37.6 years STANDARD_DEVIATION 10.4
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants	8 Participants	15 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	7 Participants	6 Participants	13 Participants
Region of Enrollment United States	7 participants	8 participants	15 participants
Sex: Female, Male Female	3 Participants	6 Participants	9 Participants
Sex: Female, Male Male	4 Participants	2 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 15	0 / 13
other Total, other adverse events	1 / 15	0 / 13
serious Total, serious adverse events	0 / 15	0 / 13

Outcome results

Primary

Area Under the Curve (AUC) of Postprandial Glucose

Incremental AUC of postprandial glucose in the 4 hours following the start of first meal. AUC (mg/dL\*hr) will be calculated using a trapezoidal method, which sums all CGM values taken every 5 minutes in the 4 hour period following the meal above the starting glucose. This yields a maximum of 48 data points for the calculation.