Three Way Crossover Closed Loop Study With Xeris Glucagon

NCT03424044 | Completed Phase 1 Results FDA Drug FDA Device

• 1 other identifier: 17225
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Closed-loop systems are an emerging technology that automate hormone delivery. They are quickly paving the way to revolutionize the treatment of type 1 diabetes. Several categories have emerged: dual-hormone (insulin and glucagon) closed-loop systems and closed-loop systems with insulin only, one variety of which is the low glucose suspend safety feature now available from Medtronic (MiniMed640G with SmartGuard). The study described within this protocol is designed to test the efficacy of a new closed-loop algorithm for managing blood glucose in people with type 1 diabetes before and after exercise. The new algorithm will have 3 modes: a single hormone insulin only mode, a dual-hormone insulin and glucagon mode and an insulin only mode with predictive low glucose suspend, all with an exercise detection algorithm. The purpose of this study is to determine whether a dual hormone AP using a stable investigational glucagon with an exercise detection algorithm outperforms both single hormone AP and a low glucose suspend algorithm.

Conditions

Type1diabetes

Keywords

glucagon; closed-loop; Omnipod; exercise

Outcome Measures

Primary Outcomes (1)

• Percent of Time With Sensed Glucose < 70 mg/dl

  Assess the percent of time that the Dexcom G5 or G6 reported sensor glucose values less than 70 mg/dl using Dexcom sensor across all three arms.

  4 hours post exercise on Day 1

Secondary Outcomes (6)

• Percent of Time With Sensed Glucose Between 70-180 mg/dl

  entire 76 hour study

• Number of Carbohydrate Treatments

  24 hours

• Percent of Time With Sensed Glucose < 54 mg/dl

  entire 76 hour study

• Percent of Time With Sensed Glucose > 180 mg/dl

  entire 76 hour study

• Mean Amount of Insulin Delivered in One Day

  24 hours

Study Arms (3)

Dual Hormone Closed-loop Arm

EXPERIMENTAL

Subjects will undergo a 76 hour study with 9 hours inpatient and 67 hours outpatient using the closed-loop artificial pancreas controller in dual hormone mode and XeriSol glucagon to manage blood sugar that includes an exercise detection component that includes a reduction in insulin delivery and an increase in glucagon delivery upon detection.

Device: Artificial Pancreas Controller in Dual Hormone Mode; Drug: XeriSol glucagon

Single Hormone Closed-loop Arm

EXPERIMENTAL

Subjects will undergo a 76 hour study with 9 hours inpatient and 67 hours outpatient using the closed-loop artificial pancreas controller in single hormone mode to manage blood sugar that includes an exercise detection component that includes a reduction in insulin delivery upon detection.

Device: Artificial Pancreas Controller in Single Hormone Mode

Predictive Low Glucose Suspend Arm

EXPERIMENTAL

Subjects will undergo a 76 hour study with 9 hours inpatient and 67 hours outpatient using the closed-loop artificial pancreas controller in predictive low glucose suspend mode. The system will run through the closed-loop system but will utilize the patient's optimized basal rates, correction factors and carb ratios as they would normally run on their own insulin pump. But the mode will have the additional safety net of the pump suspending insulin when it predicts a hypoglycemic event.

Device: Artificial Pancreas Controller in Predictive Low Glucose Suspend Mode

Interventions

Artificial Pancreas Controller in Dual Hormone Mode DEVICE

The artificial pancreas controller contains an algorithm for managing blood glucose in people with type 1 diabetes which includes an exercise detection component. The algorithm has 3 modes: a single hormone closed-loop insulin only mode, a dual-hormone closed-loop insulin and glucagon mode and an insulin only mode with predictive low glucose suspend. The Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G5 sensor and sending delivery commands to two Omnipod insulin pumps, one filled with insulin and one with glucagon.

Dual Hormone Closed-loop Arm

Artificial Pancreas Controller in Single Hormone Mode DEVICE

The artificial pancreas controller contains an algorithm for managing blood glucose in people with type 1 diabetes which includes an exercise detection component. The new algorithm will have 3 modes: a single hormone closed-loop insulin only mode, a dual-hormone closed-loop insulin and glucagon mode and an insulin only mode with predictive low glucose suspend. The Closed-loop Artificial Pancreas Controller includes insulin delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G5 sensor and sending delivery commands to one Omnipod pump filled with insulin.

Single Hormone Closed-loop Arm

Artificial Pancreas Controller in Predictive Low Glucose Suspend Mode DEVICE

The artificial pancreas controller contains an algorithm for managing blood glucose in people with type 1 diabetes which includes an exercise detection component. The new algorithm will have 3 modes: a single hormone closed-loop insulin only mode, a dual-hormone closed-loop insulin and glucagon mode and an insulin only mode with predictive low glucose suspend. The Closed-loop Artificial Pancreas Controller includes insulin delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G5 sensor and sending delivery commands to one Omnipod insulin pump filled with insulin.

Predictive Low Glucose Suspend Arm

XeriSol glucagon DRUG

XeriSol glucagon is an investigational drug that is a stable, soluble liquid glucagon formulation that can be injected or administered through an insulin pump. XeriSol glucagon will be used to fill the Omnipod to deliver glucagon for the Artificial Pancreas Controller in Dual Hormone mode.

Dual Hormone Closed-loop Arm

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of type 1 diabetes mellitus for at least 1 year.
• Male or female subjects 21-50 years of age.
• Physically willing and able to perform 45 min of exercise.
• Current use of an insulin pump.
• Lives with another person age 18 or older who will be present while subject exercises at home and that can attend the training on using the system.
• Lives within 40 miles of OHSU main campus.
• HbA1c \<= 10% at screening.
• Total daily insulin requirement is less than 139 units/day.
• Current use of a phone or other device so can be contacted by study staff off-campus.
• Willingness to follow all study procedures, including attending all clinic visits.
• Willingness to sign informed consent and HIPAA documents.

You may not qualify if:

• 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.
• Renal insufficiency (GFR \< 60 ml/min, using the MDRD equation as report 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.
• Hypertensive subjects with systolic blood pressure \>= 160 mm Hg or diastolic blood pressure \>= 100 mm Hg despite treatment or who have treatment-refractory hypertension (e.g. requiring four or more medications).
• History of severe hypoglycemia during the past 12 months prior to screening visit or hypoglycemia unawareness as judged by the investigator. Subjects will complete a hypoglycemia awareness questionnaire. Subjects will be excluded for four or more R responses.
• 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).

Sponsors & Collaborators

• Oregon Health and Science University: lead
• Xeris Pharmaceuticals: collaborator

Study Sites (1)

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Wilson LM, Jacobs PG, Ramsey KL, Resalat N, Reddy R, Branigan D, Leitschuh J, Gabo V, Guillot F, Senf B, El Youssef J, Steineck IIK, Tyler NS, Castle JR. Dual-Hormone Closed-Loop System Using a Liquid Stable Glucagon Formulation Versus Insulin-Only Closed-Loop System Compared With a Predictive Low Glucose Suspend System: An Open-Label, Outpatient, Single-Center, Crossover, Randomized Controlled Trial. Diabetes Care. 2020 Nov;43(11):2721-2729. doi: 10.2337/dc19-2267. Epub 2020 Sep 9.

  PMID: 32907828 DERIVED

MeSH Terms

Conditions

Motor Activity

Condition Hierarchy (Ancestors)

Behavior

Results Point of Contact

• Title: Jessica Castle MD
• Organization: Oregon Health and Science University

castleje@ohsu.edu

503-494-7072

Study Officials

• Jessica Castle, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 31, 2018
• First Posted: February 6, 2018
• Study Start: March 29, 2018
• Primary Completion: May 17, 2019
• Study Completion: May 17, 2019
• Last Updated: May 27, 2020
• Results First Posted: May 13, 2020

Record last verified: 2020-05

Locations

US (1)