WBH002: Artificial Pancreas Technology to Reduce Glycemic Variability and Improve Cardiovascular Health in Type 1 Diabetes

Sponsor

University of Virginia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05653518

Collaborator

(none)

Enrollment

Arms

34.5

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Device: Tandem t:slim X2 with Control-IQ Technology Device: Sensor augmented pump (SAP) therapy	N/A

Detailed Description

Cardiovascular disease is a type of disease that affects the heart and blood vessels. The current care for cardiovascular disease prevention in people with type 1 diabetes is to manage blood pressure, cholesterol blood levels, or manage blood glucose levels.

This study will examine the potential cardiovascular effect(s) of artificial pancreas (AP) technology in patients with type 1 diabetes. AP technology is a system of devices that closely mimics the glucose-regulating function of a healthy human pancreas. It includes an insulin pump and a continuous glucose monitor (CGM). In this study, we will use the Food and Drug Administration (FDA)-approved Tandem t:slim insulin pump with Control-IQ Technology and the FDA approved Dexcom G6 CGM. This study will research whether improvements in blood glucose metrics lead to reductions in some of the cardiovascular biomarkers that represent harmful effects in people with type 1 diabetes. Subjects will be randomly assigned to one of two study groups for 12 weeks---Group 1 will be treated with AP Technology and Group 2 will wear the study CGM and continue to use their current diabetes management strategy (i.e., standard care).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Using Closed-Loop Artificial Pancreas Technology to Reduce Glycemic Variability and Subsequently Improve Cardiovascular Health in Type 1 Diabetes

Anticipated Study Start Date :

Jan 15, 2023

Anticipated Primary Completion Date :

Nov 30, 2025

Anticipated Study Completion Date :

Nov 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Closed-loop artificial pancreas (AP) FDA approved Tandem t:slim insulin pump with Control-IQ Technology and the Dexcom G6 CGM	Device: Tandem t:slim X2 with Control-IQ Technology FDA approved Tandem t:slim insulin pump with Control-IQ Technology and the Dexcom G6 CGM
Experimental: Sensor Augmented Pump (SAP) therapy Sensor augmented pump (SAP) therapy that includes the use of a study CGM and the participant's current insulin therapy (i.e., either insulin pump or multiple daily injections)	Device: Sensor augmented pump (SAP) therapy Sensor augmented pump (SAP) therapy that includes the use of a study CGM and the participant's personal insulin pump

Arm

Intervention/Treatment

Experimental: Closed-loop artificial pancreas (AP)

FDA approved Tandem t:slim insulin pump with Control-IQ Technology and the Dexcom G6 CGM

Device: Tandem t:slim X2 with Control-IQ Technology

FDA approved Tandem t:slim insulin pump with Control-IQ Technology and the Dexcom G6 CGM

Experimental: Sensor Augmented Pump (SAP) therapy

Sensor augmented pump (SAP) therapy that includes the use of a study CGM and the participant's current insulin therapy (i.e., either insulin pump or multiple daily injections)

Device: Sensor augmented pump (SAP) therapy

Sensor augmented pump (SAP) therapy that includes the use of a study CGM and the participant's personal insulin pump

Outcome Measures

Primary Outcome Measures

Glucose Time-in-Range [12 weeks]
Time-in-range will measured by continuous glucose monitor device

Secondary Outcome Measures

High-sensitivity C-reactive protein (hs-CRP) [At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks]
Inflammatory Biomarker
TNF-alpha [At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks]
Inflammatory Biomarker
Interleukin-6 (IL-6) [At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks]
Inflammatory Biomarker
E-selectin [At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks]
Biomarker of endothelial dysfunction
Intracellular adhesion molecule 1 (ICAM-1) [At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks]
Biomarker of endothelial dysfunction
Malondialdehyde (MDA) [At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks]
Biomarker of Oxidative Stress
Asymmetric Dimethylarginine (ADMA) [At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks]
Biomarker of Endothelial Cell Oxidative Stress

Other Outcome Measures

Myocardial Perfusion (measured by contrast-enhanced ultrasound [CEU]) [At baseline and after 12 weeks of treatment]
CEU will be assessed before and after regadenoson infusion to measure myocardial microvascular perfusion
Carotid Femoral Pulse Wave Velocity (cfPWV) [At baseline and after 12 weeks of treatment]
Measurement of change in central artery stiffness
Flow-Mediated Dilation (FMD) [At baseline and after 12 weeks of treatment]
Vascular measure of change in conduit artery stiffness
Human CD14+ monocytes [At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks]
Inflammatory Immune cells associated with atherosclerosis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Clinical diagnosis, based on World Health Organization criteria, of type 1 diabetes for at least one year
Currently using insulin for at least six months
Ages 18-≤40 years
Hemoglobin A1c <10.5%
Body mass index 18-30 kg/m2
Blood pressure <140/90 mmHg
For females, not currently known to be pregnant or breastfeeding
If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative serum or urine pregnancy test will be required for all females of childbearing potential. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued
Both pump and MDI users will use insulin parameters such as carbohydrate ratio and correction factors consistently in order to dose insulin for meals or corrections; pump users will have history of entering this information into their pump
Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use
Access to internet and willingness to upload data during the study as needed, including data generated prior to the start of the study
Current use of a glucometer that is downloadable; or willingness to use a study glucometer
Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol
Willingness to use personal lispro (Humalog) or aspart (Novolog) and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study
Total daily insulin dose (TDD) at least 10 U/day.
Willingness not to start any new non-insulin glucose-lowering agent during the trial

Exclusion Criteria:

Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment
Diagnosis of diabetic ketoacidosis in the 12 months prior to enrollment
Prior diagnosis of cardiac disease (e.g. myocardial infarction, congestive heart failure)
Cerebrovascular accident in the 12 months prior to enrollment
Conditions that would make use of a CGM difficult (e.g., blindness, severe arthritis, immobility)
Current use of oral/inhaled glucocorticoids or other medications, which in the judgment of the investigator would be a contraindication to participation in the study
Concurrent use of any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas)
Hemophilia or any other bleeding disorder
Currently being treated for a seizure disorder
A medical condition or medication, which in the opinion of the investigator or designee, would put the participant or study at risk
Current use of an automated insulin delivery system (besides LGS and PLGS) such as Medtronic 670G, Control-IQ or DIY system (or unwillingness to discontinue automated insulin delivery for three months before enrollment and the duration of the trial)
Current smokers or those who have quit smoking <2 years ago
Screening Electrocardiogram (ECG) findings indicative of arrhythmia, sinus node disease, or ischemic heart disease
Diagnosis of peripheral neuropathy (assessed by monofilament examination), macroalbuminuria (urine albumin:creatinine >300 mg per g), or retinopathy beyond mild, nonproliferative retinopathy
Unstable (i.e., dose adjustment less than 4 weeks prior to study enrollment) doses of vasoactive medications (e.g., calcium channel blockers, statins, nitrates, alpha-blockers, beta-blockers, ACE inhibitors, etc.)
Uncontrolled resting arterial hypertension
History of hypersensitivity or prior adverse reaction to Definity Microbubble Infusion
History of hypersensitivity or prior adverse reaction to regadenoson Infusion
Current enrollment in another clinical trial, unless approved by the investigator of both studies or if clinical trial is a non-interventional registry trial