Clinical trial NCT05653518: Artificial Pancreas Technology to Reduce Glycemic Variability and Improve Cardiovascular Health in Type 1 Diabetes
Official title: Using Closed-Loop Artificial Pancreas Technology to Reduce Glycemic Variability and Subsequently Improve Cardiovascular Health in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 1 Diabetes
Keywords: Glycemic Variability
Inflammation
Oxidative Stress
Endothelial Function
Myocardial Perfusion
Aortic Stiffness
Flow-Mediated Dilation
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2022-12-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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, the investigators will research whether improvements in blood glucose levels and blood glucose variability will in turn decrease biomarkers of inflammation and endothelial dysfunction while improving cardiovascular function.

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).

Eligibility criteria: Inclusion Criteria:

1. Clinical diagnosis, based on World Health Organization criteria, of type 1 diabetes for at least one year
2. Currently using insulin for at least six months
3. Ages 18-≤40 years
4. Hemoglobin A1c \<10.5%
5. Body mass index 18-30 kg/m2
6. Blood pressure \<140/90 mmHg
7. For females, not currently known to be pregnant or breastfeeding
8. 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
9. 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
10. Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use
11. Access to internet and willingness to upload data during the study as needed, including data generated prior to the start of the study
12. Current use of a glucometer that is downloadable; or willingness to use a study glucometer
13. Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol
14. Willingness to use personal lispro (Humalog) or aspart (Novolog) and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study
15. Total daily insulin dose (TDD) at least 10 U/day.
16. Willingness not to start any new non-insulin glucose-lowering agent during the trial

Exclusion Criteria:

1. Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment
2. Diagnosis of diabetic ketoacidosis in the 12 months prior to enrollment
3. Prior diagnosis of cardiac disease (e.g., myocardial infarction, congestive heart failure)
4. Cerebrovascular accident in the 12 months prior to enrollment
5. Uncontrolled resting arterial hypertension
6. Conditions that would make use of a CGM difficult (e.g., blindness, severe arthritis, immobility)
7. 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
8. Concurrent use of any non-insulin glucose-lowering agent (including metformin, GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, and/or sulfonylureas)
9. Hemophilia or any other bleeding disorder
10. Currently being treated for a seizure disorder
11. A medical condition or medication, which in the opinion of the investigator or designee, would put the participant or study at risk
12. Current smokers or those who have quit smoking \<2 years ago
13. Screening Electrocardiogram (ECG) findings indicative of arrhythmia, sinus node disease, or ischemic heart disease
14. Any woman with hemoglobin (Hgb) \<11 g/dL or any man with Hgb \<12 g/dL on screening laboratory evaluation (i.e., complete blood count)
15. History of hypersensitivity or prior adverse reaction (e.g., anaphylaxis or angioedema) to IV regular insulin infusion
16. Diagnosis of peripheral neuropathy (assessed by monofilament examination), macroalbuminuria (urine albumin:creatinine \>300 mg per g), or retinopathy beyond mild, nonproliferative retinopathy
17. 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.)
18. History of hypersensitivity or prior adverse reaction to Definity microbubble infusion
19. Current enrollment in another clinical trial, unless approved by the investigator of both studies or if clinical trial is a non-interventional registry trial

Primary outcomes:
measure: Glucose Time-in-Range
timeFrame: 12 weeks
Secondary outcomes:
measure: High-sensitivity C-reactive protein (hs-CRP)
timeFrame: At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks
measure: TNF-alpha
timeFrame: At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks
measure: Interleukin-6 (IL-6)
timeFrame: At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks
measure: E-selectin
timeFrame: At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks
measure: Intracellular adhesion molecule 1 (ICAM-1)
timeFrame: At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks
measure: Myocardial Perfusion (measured by contrast-enhanced ultrasound [CEU])
timeFrame: At baseline and 12 weeks of treatment
measure: Carotid Femoral Pulse Wave Velocity (cfPWV)
timeFrame: At baseline and 12 weeks of treatment
measure: Brachial artery flow-mediated dilation (FMD)
timeFrame: At baseline and 12 weeks of treatment
measure: Insulin sensitivity
timeFrame: At baseline and 12 weeks of treatment
Other outcomes:
measure: Human CD14+CD16- monocytes
timeFrame: At baseline (0 weeks), 3 weeks, 6 weeks, 9 weeks, and 12 weeks
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: University of Virginia
name: William B Horton, MD
role: PRINCIPAL_INVESTIGATOR
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