Clinical trial NCT03528174: Single Hormone Closed Loop Study With PDT Sensor
Official title: Assessment of a Novel Sensing Catheter During Automated Insulin Delivery in Patients With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2018-05-17
Enrollment: 10
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DEVICE_FEASIBILITY

Brief summary: The study described within this protocol is designed to test a single hormone closed-loop algorithm for managing blood glucose in type 1 diabetes using insulin only and a new device for measuring glucose continuously in the immediate vicinity of subcutaneous insulin delivery. Subjects will undergo one all day closed loop study using insulin only. The closed loop insulin only system includes a Dexcom G5 transmitter, a Nexus 5 smart phone and two Tandem tslim pumps connected to two Pacific Diabetes Technologies glucose sensing cannulas. The closed loop system will be started after G5 2 hour sensor start-up with an IV catheter for frequent blood withdrawal for 10 hours.

Detailed description: Subjects will undergo one 12 hour inpatient study. During this intervention visit, subjects will wear the single hormone closed loop system which includes two t:slim insulin pumps to deliver insulin or saline through two investigational PDT glucose sensing cannulas, and a Dexcom G5 CGM to measure glucose. The subject will come to the research center at approximately 7am for the inpatient visit. The Dexcom G5 sensor and PDT glucose sensing cannulas will be placed after arrival. An 18-22 gauge IV catheter will be placed for blood sampling every 15 minutes after sensor warm-up is complete for measuring blood glucose concentration. After a 2 hour warm-up period for the G5 sensor, glucose will be controlled using the FMPD single hormone mode. The single hormone mode of the controller determines insulin delivery rates based on proportional and derivative error through one t:slim insulin pump. The second t:slim insulin pump will deliver normal saline at the same delivery rates as the insulin. Subjects will eat breakfast and lunch at approximately 11 am and 3 pm respectively. Subjects will have the ability to complete light exercise on a treadmill. The closed loop system will be stopped at approximately 6pm with removal of all devices.

During the study, the subject will wear one subcutaneous DexcomTM G5 continuous glucose monitoring (CGM) system. The CGM system will provide sensed glucose data every 5 minutes. The accuracy of the sensed data will be obtained by reference measurements of two YSI venous blood glucose values to calibrate the sensor at the beginning of the closed loop study. Sensed glucose data will be wirelessly transmitted via Bluetooth Low Energy (BTLE) from the Dexcom G5 transmitter to the Nexus 5 master controller every five minutes. The controller is a Google Nexus 5 phone. The smart phone will wirelessly communicate via BTLE to two Tandem t:slim insulin pumps, one for automated insulin delivery and one of automated saline delivery.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of type 1 diabetes mellitus for at least 1 year.
* Male or female subjects 21 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% at screening.
* Body Mass Index ≥ 22.
* Total daily insulin requirement is less than 200 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 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.
* 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.
* History of Diabetic 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 lispro insulin.
* Allergy to acrylate-based skin adhesives.
* Need for uninterrupted treatment of acetaminophen.
* 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).
* Any clinically significant disease or disorder which in the opinion of the Investigator may jeopardize the subject's safety or compliance with the protocol.

Primary outcomes:
measure: Mean Absolute Relative Difference of Sensed Glucose Values
timeFrame: up to 10 hours
Secondary outcomes:
measure: Percent of Time With Sensed Glucose Between 70-180 mg/dl
timeFrame: up to 10 hours
measure: Percent of Time With Sensed Glucose Less Than 70 mg/dl
timeFrame: up to 10 hours
measure: Percent of Time With Sensed Glucose Less Than 54 mg/dl
timeFrame: up to 10 hours
measure: Percent of Time With Sensed Glucose Greater Than 250 mg/dl
timeFrame: up to 10 hours
measure: Mean Sensed Glucose
timeFrame: up to 10 hours
measure: Number of Carbohydrate Treatments
timeFrame: up to 10 hours
measure: Mean Amount of Insulin Delivered
timeFrame: up to 10 hours
measure: Mean Score of Visual Analog Scale at 15 Minutes
timeFrame: 15 minutes post insertion
measure: Mean Score of Visual Analog Scale at 120 Minutes
timeFrame: 120 minutes post insertion
measure: Mean Score of Visual Analog Scale at End of Study
timeFrame: End of 10 hour study
measure: Mean Draize Scale for Erythema for the Left Sensing Cannula at End of Study for All Subjects
timeFrame: End of 10 hour study
measure: Mean Draize Scale for Edema for the Left Sensing Cannula at End of Study for All Subjects
timeFrame: end of 10 hour study
measure: Mean Draize Scale for Erythema for the Right Sensing Cannula at End of Study for All Subjects
timeFrame: End of 10 hour study
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: Jessica Castle, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oregon Health and Science University
name: Peter Jacobs, PhD
role: PRINCIPAL_INVESTIGATOR
References: