USS Virginia Closed-Loop Versus SAP Therapy for Hypoglycemia Reduction in T1D

NCT02302963 | Completed Results DMC

• 2 other identifiers: 177251DP3DK101055
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 2

Brief Summary

This is a randomized, controlled trial of Unified Safety System (USS) Virginia closed-loop versus sensor-augmented pump (SAP) therapy for hypoglycemia prevention in subjects with type 1 diabetes and hypoglycemia unawareness and/or risk for hypoglycemia.

Conditions

Type 1 Diabetes Mellitus

Keywords

Diabetes Mellitus, Type 1 (T1DM); Diabetes Assistant (DiAs); Artificial Pancreas (AP) System; Closed-Loop Control (CLC); Unified Safety System (USS) Virginia; Sensor Augmented Pump (SAP); Low Blood Glucose Index (LBGI); Continuous Glucose Monitor (CGM); inControl Diabetes Management Platform

Outcome Measures

Primary Outcomes (1)

• Change in Hypoglycemia During Closed Loop Control (Assessed by Low Blood Glucose Index [LBGI])

  Change in hypoglycemia during the study on USS Virginia versus Sensor Augmented Pump (SAP) as assessed by Low Blood Glucose Index (LBGI) from Continuous Glucose Monitoring (CGM) during 1 week of baseline blinded use versus during the last week of intervention. The LBGI is a metric of the frequency and severity of hypoglycemia, based on an increasing weighting of progressively low glucose readings. The LBGI will be higher for someone with a higher percentage of low blood glucose readings or more extreme hypoglycemic episodes. Reference: Kovatchev BP. Metrics for Glycaemic Control: from HbA1c to Continuous Glucose Monitoring. Nature Reviews Endocrinology 2017; 13: 425-436. PMID: 28304392

  2 weeks total: one week of baseline blinded use to compute LBGI-Pre versus use during the last week of intervention to compute LBGI-Post

Study Arms (2)

AP System (DiAs or inControl) with USS Virginia

EXPERIMENTAL

Subject will complete an 8-hour inpatient assessment of hypoglycemia counterregulation. Subject will then proceed through 7 weeks of training and use of the AP System with USS Virginia and study pump. The inpatient testing will be repeated after wearing the AP System at home.

Device: AP System (DiAs or inControl) with USS Virginia

Sensor-Augmented Pump Therapy

PLACEBO COMPARATOR

Subject will complete an 8-hour inpatient assessment of hypoglycemia counterregulation. Subject will then wear a continuous glucose monitor and their own insulin pump at home for 5 weeks. The inpatient testing will be repeated at the completion of the 5 weeks at home.

Device: Sensor-Augmented Pump Therapy (placebo)

Interventions

AP System (DiAs or inControl) with USS Virginia DEVICE

Subject will participate in two 24-hour study insulin pump and AP System training sessions. At the conclusion of each training session, subject will wear the equipment at home for a total of 5 weeks.

AP System (DiAs or inControl) with USS Virginia

Sensor-Augmented Pump Therapy (placebo) DEVICE

Subject will participate in 5 weeks use of CGM and personal insulin pump at home.

Sensor-Augmented Pump Therapy

Eligibility Criteria

• Age: 12 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of type 1 diabetes for at least 1 year. For an individual to be enrolled at least one criterion from each list must be met:
• Criteria for documented hyperglycemia (at least 1 must be met):
• Fasting glucose ≥126 mg/dL (confirmed)
• Two-hour oral glucose tolerance test (OGTT) glucose ≥200 mg/dL (confirmed)
• HbA1c ≥6.5% (confirmed)
• Random glucose ≥200 mg/dL with symptoms
• No data at diagnosis is available but the participant has a convincing history of hyperglycemia consistent with diabetes or in the opinion of the investigator participant has history consistent with type 1 diabetes.
• Criteria for requiring insulin at diagnosis (at least 1 must be met):
• Participant required insulin at diagnosis and continually thereafter
• Participant did not start insulin at diagnosis but upon investigator review likely needed insulin (significant hyperglycemia that did not respond to oral agents) and did require insulin eventually and used continually
• Participant required insulin at diagnosis but continued to be hyperglycemic, had positive islet cell antibodies - consistent with latent autoimmune diabetes in adults (LADA) and did require insulin eventually and used continually thereafter
• Use of insulin for the last 12 months or more
• Use of an insulin infusion pump for the last 6 months or longer
• Age 12-70 years old
• HbA1c \<10.0% as measured with DCA2000 or equivalent device; if HbA1c \<6.0% then total daily insulin must be ≥0.5 U/kg

You may not qualify if:

• Admission for diabetic ketoacidosis in the 12 months prior to enrollment.
• Severe hypoglycemia resulting in seizure or loss of consciousness in the 3 months prior to enrollment.
• Hematocrit less that the lower limit of normal for the assay.
• Pregnancy, breast-feeding, or intention of becoming pregnant over time of study procedures; If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative urine pregnancy test will be required for all premenopausal women who are not surgically sterile. Subjects who become pregnant will be discontinued from the study.
• Conditions which may increase the risk of induced hypoglycemia such as: known coronary artery disease, congestive heart failure, history of any cardiac arrhythmia (benign premature atrial contractions and premature ventricular contractions allowed), history of seizure disorder, history of cerebrovascular event or transient ischemic attack, hypoglycemia-induced migraine within the last 6 months, or neurological disease.
• Cystic fibrosis
• A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:
• Inpatient psychiatric treatment in the past 6 months for either the subject or the subject's diabetes care partner
• Presence of a known adrenal disorder
• Abnormal liver function tests (transaminase \>3 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function
• Abnormal renal function test results (estimated Glomerular filtration rate (GFR) \<60 mL/min/1.73m2); testing required for subjects with diabetes duration of greater than 5 years post onset of puberty
• Active gastroparesis
• If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study
• Uncontrolled thyroid disease (TSH undetectable or \>10 mIU/L); testing required within 3 months prior to admission for subjects with a goiter, positive antibodies, or who are on thyroid hormone replacement, and within one year otherwise
• Current or recent abuse of alcohol or recreational drugs by patient history

Sponsors & Collaborators

• University of Virginia: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Stanford University: collaborator
• TypeZero Technologies, LLC: collaborator

Study Sites (2)

Stanford University

Stanford, California, 94305, United States

Location

University of Virginia Center for Diabetes Technology

Charlottesville, Virginia, 22903, United States

Location

Related Publications (1)

• Anderson SM, Buckingham BA, Breton MD, Robic JL, Barnett CL, Wakeman CA, Oliveri MC, Brown SA, Ly TT, Clinton PK, Hsu LJ, Kingman RS, Norlander LM, Loebner SE, Reuschel-DiVirglio S, Kovatchev BP. Hybrid Closed-Loop Control Is Safe and Effective for People with Type 1 Diabetes Who Are at Moderate to High Risk for Hypoglycemia. Diabetes Technol Ther. 2019 Jun;21(6):356-363. doi: 10.1089/dia.2019.0018. Epub 2019 May 16.

  PMID: 31095423 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

CGM data were missing for 2 of the 44 subjects (1 control and 1 experimental) and outcomes could not be reliably computed. Therefore, 42 subjects were included in the final analysis.

Results Point of Contact

• Title: Director
• Organization: University of Virginia Center for Diabetes Technology

bpk2u@virginia.edu

434-924-5592

Study Officials

• Stacey M. Anderson, MD

  UVA Center for Diabetes Technology

  PRINCIPAL INVESTIGATOR

• Bruce Buckingham, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2014
• First Posted: November 27, 2014
• Study Start: June 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: October 7, 2022
• Results First Posted: October 7, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After publication of the primary manuscript, published in Diabetes Technology and Therapeutics, Volume 21, Number 6, 2019
• Access Criteria: Study outcomes are presented in the primary manuscript. Raw data can be shared via data sharing agreement, as described in the Data Sharing Plan.

Locations

US (2)