USS Virginia Closed-Loop for Overnight Control in Type 1 Diabetes

• Sponsor: University of Virginia (Other)
• Overall Status: Completed
• CT.gov ID: NCT02131766
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 33
• Locations: 4
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to use the USS Virginia Closed-Loop system for overnight insulin delivery in adults with Type 1 Diabetes (T1DM) in an outpatient setting to evaluate the system's ability to significantly improve blood glucose levels. This protocol will test the feasibility of "bedside" closed-loop control - an approach comprised of standard sensor-augmented pump therapy during the day using off-the-shelf devices and overnight closed-loop control using experimental devices in an outpatient setting. The rationale for this study is as follows: we anticipate that closed-loop control may ultimately be adopted by patients with T1DM in a selective manner. Patient may choose to start using these systems for overnight control only, e.g. to alleviate the well documented fear of hypoglycemia while asleep. To test this paradigm of "bedside" closed-loop control, subjects will be studied with continuous glucose monitoring (CGM)-augmented usual pump therapy during the day followed by overnight use of USS Virginia Closed Loop Control.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus	Device: DiAs; Other: Sensor Augmented Pump Therapy	N/A

Detailed Description

The subject will participate in both the Experimental and the Control Admissions. The order of the two admissions will be randomized. During the Control Admission at home, the subject will use the study insulin pump along with a continuous glucose monitor receiver. During the Experimental Admission, the subject will be the research house/hotel where the subject will be in control of the DiAs. Participation in this study will require 5 study visits over 11-14 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Unified Safety System (USS) Virginia Closed-Loop Versus Sensor Augmented Pump Therapy for Overnight Control in Type 1 Diabetes
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: USS Virginia Closed Loop Control The subject will be admitted to the research house/hotel and will be discharged after 5 nights. The subject will be trained on DiAs and on how to respond to the system's alerts. The DiAs will be initiated by 11:00 PM and will be discontinued before breakfast. The staff will be monitoring the subject remotely. The subject will need to remain within a 30 miles of the research house/hotel during the day and return by 6:00 PM. A limited number of UVA and UPadova subjects will be asked to wear the DiAs at home for 5 days at the conclusion of research house admission.	Device: DiAs; DiAs is the central component of our system. It is a standard cell phone running on an Android operating system. The cell phone has been changed to prevent from (1) using it as a phone or browser, (2) changing the volume (3) accidentally shutting it off. The cell phone runs an algorithm and is connected to work with the insulin pump and continuous glucose monitor to help keep the blood sugar in a desired range and help avoid hypoglycemia during the night.
Placebo Comparator: Sensor Augmented Pump Therapy The subject will wear the continuous glucose monitor with the study insulin pump for a full 7 day period (approximately 7 consecutive 24 hour periods). The subject will follow their usual regimen. The subject will be asked to use the bolus calculator function on your insulin pump and enter the carbohydrate information that you eat during the week.	Other: Sensor Augmented Pump Therapy; Insulin pump plus CGM.; Other Names: SAP

Outcome Measures

Primary Outcome Measures

1. USS Virginia Time Within Target [40 hours]

   Assess the effect size of USS Virginia in increasing time within target (70-180 mg/dL) over a 24-hour period with closed-loop control overnight (23:00 to 07:00) as compared to sensor-augmented pump alone.

Secondary Outcome Measures

1. Overnight Target Range [40 hours]

   Assess time spent within target range of 80-140 mg/dl overnight with USS Virginia Closed Loop compared to sensor-augmented pump therapy alone

2. Decreased Overnight Hypoglycemia [40 hours]

   Assess the effect of USS Virginia Closed Loop System to decrease hypoglycemia overnight compared to sensor-augmented pump therapy alone

3. Morning Glucose Levels [40 hours]

   Assess the distribution of wake-up glucose levels at 07:00 achieved by USS Virginia Closed Loop vs. to sensor-augmented pump therapy alone;

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year and an insulin pump for at least 6 months

• Criteria for documented hyperglycemia (at least 1 must be met): i. Fasting glucose ≥126 mg/dL ii. Two-hour Oral Glucose Tolerance Test (OGTT) glucose ≥200 mg/dL iii. HbA1c ≥6.5% documented iv. Random glucose ≥200 mg/dL with symptoms v. No data at diagnosis is available but the participant has a convincing history of hyperglycemia consistent with diabetes.

• Criteria for requiring insulin at diagnosis (1 must be met): i. Participant required insulin at diagnosis and continually thereafter ii. 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 iii. Participant did not start 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

1. Age ≥21 to <65 years

2. HbA1c <10.0%

3. For females, not currently known to be pregnant 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.

4. Demonstration of proper mental status and cognition for the study

5. Currently using insulin-to-carbohydrate ratio to calculate meal bolus sizes

6. Ability to access the Internet and upload CGM data via the DexCom company software during the data collection period.

7. Willingness to remain within approximately 30 miles radius of study site during the day time hours of Visit 4.

8. An understanding of and willingness to follow the protocol and sign the informed consent

Additional Inclusion Criteria for UVA subjects only who participate in the 5 days at-home portion

• Availability of a significant other or family member committed to participating in all training activities, knowledgeable at all times of the participant's location, and being present and available to provide assistance when system is being used at night

• Commitment to maintaining uninterrupted availability via cell phone and avoiding any overnight travel for the duration of the period of time using the closed-loop system at home.

• Access to internet and cell phone service at home

Exclusion Criteria:

1. Admission for diabetic ketoacidosis in the 12 months prior to enrollment

2. Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment

3. History of a seizure disorder (except hypoglycemic seizure), unless written clearance is received from a neurologist

4. Coronary artery disease or heart failure, unless written clearance is received from a cardiologist

5. Cystic fibrosis

6. 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

• Presence of a known adrenal disorder

• Abnormal liver function test results (Transaminase >2 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 (calculated 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 mlU/L); testing required within three months prior to admission for subjects with a goiter, positive antibodies, or who are on thyroid hormone replacement, and within one year otherwise

• Abuse of alcohol or recreational drugs

• Infectious process not anticipated to resolve prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis).

• Uncontrolled arterial hypertension (Resting diastolic blood pressure >90 mmHg and/or systolic blood pressure >160 mmHg).

• Oral steroids

• Uncontrolled microvascular complications such as current active proliferative diabetic retinopathy defined as proliferative retinopathy requiring treatment (e.g. laser therapy) in the past 12 months.

1. A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the protocol

2. Basal Rates <0.01 units/hour.

3. Current use of the following drugs and supplements:

• Acetaminophen

• Any medication being taken to lower blood glucose, such as Pramlintide, Metformin, glucagon-like peptide (GLP)-1 Analogs such as Liraglutide, and nutraceuticals intended to lower blood glucose

• Beta blockers

• Any other medication that the investigator believes is a contraindication to the subject's participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905
2	Mount Sinai Hospital	New York	New York	United States	10029-6574
3	University of Virginia Center for Diabetes Technology	Charlottesville	Virginia	United States	22903
4	University of Padova	Padova		Italy	35131

Sponsors and Collaborators

• University of Virginia
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Sue Brown, MD, University of Virginia
• Principal Investigator: Carol Levy, MD, CDE, MOUNT SINAI HOSPITAL
• Principal Investigator: Yogish C. Kudva, MBBS, MD, Mayo Clinic
• Principal Investigator: Claudio Cobelli, PhD, University of Padova

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sue Brown, Principal Investigator, University of Virginia
• ClinicalTrials.gov Identifier: NCT02131766
• Other Study ID Numbers: 17351; 1DP3DK101055-01; NCT02008188
• First Posted: May 6, 2014
• Last Update Posted: Apr 16, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Sue Brown, Principal Investigator, University of Virginia: Diabetes Mellitus, Type 1; Artificial Pancreas Project (APP); Diabetes Assistant (DiAs); Closed-Loop Control (CLC)
• Additional relevant MeSH terms: Diabetes Mellitus

Study Results

Participant Flow

Pre-assignment Detail	These results for 40 participants who completed the trial represent the combined results from participants at UVA, Mt. Sinai and Mayo Clinic (NCT02131766) combined with participants at University of Padua in Italy (NCT02008188).

Arm/Group Title	USS Virginia Closed Loop Control and SAP
Arm/Group Description	The subject will be admitted to the research house/hotel and will be discharged after 5 nights. The subject will be trained on DiAs and on how to respond to the system's alerts. The DiAs will be initiated by 11:00 PM and will be discontinued before breakfast. The staff will be monitoring the subject remotely. The subject will need to remain within a 30 miles of the research house/hotel during the day and return by 6:00 PM. A limited number of UVA and UPadova subjects will be asked to wear the DiAs at home for 5 days at the conclusion of research house admission. DiAs: DiAs is the central component of our system. It is a standard cell phone running on an Android operating system. The cell phone has been changed to prevent from (1) using it as a phone or browser, (2) changing the volume (3) accidentally shutting it off. The cell phone runs an algorithm and is connected to work with the insulin pump and continuous glucose monitor to help keep the blood sugar in a desired range and
Period Title: Overall Study
STARTED	44
COMPLETED	40
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	USS Virginia Closed Loop Control vs SAP
Arm/Group Description	This is a cross-over trial in which each subject participates in two phases: USS Virginia Closed Loop Control (CLC) and Sensor Augmented Pump Therapy (SAP) and is randomized to order. During CLC: The subject will be admitted to the research house/hotel and will be discharged after 5 nights. The DiAs (CLC controller) will be initiated by 11:00 PM and will be discontinued before breakfast. During SAP: The subject will wear the continuous glucose monitor with the study insulin pump for a full 7 day period (approximately 7 consecutive 24 hour periods). The subject will follow their usual regimen. A limited number of UVA and UPadova subjects will be asked to wear the DiAs at home for 5 days at the conclusion of research house admission.
Overall Participants	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.5 (9.5)
Sex: Female, Male (Count of Participants)
Female	22 55%
Male	18 45%
Region of Enrollment (participants) [Number]
United States	28 70%
Italy	12 30%

Outcome Measures

1. Primary Outcome

Title	USS Virginia Time Within Target
Description	Assess the effect size of USS Virginia in increasing time within target (70-180 mg/dL) over a 24-hour period with closed-loop control overnight (23:00 to 07:00) as compared to sensor-augmented pump alone.
Time Frame	40 hours

Outcome Measure Data

Analysis Population Description

Cross-over trial with same subjects participating in both arms for a total of 40 subjects.

Arm/Group Title	USS Virginia Closed Loop Control	Sensor Augmented Pump Therapy
Arm/Group Description	The subject will be admitted to the research house/hotel and will be discharged after 5 nights. The subject will be trained on DiAs and on how to respond to the system's alerts. The DiAs will be initiated by 11:00 PM and will be discontinued before breakfast. The staff will be monitoring the subject remotely. The subject will need to remain within a 30 miles of the research house/hotel during the day and return by 6:00 PM. A limited number of UVA and UPadova subjects will be asked to wear the DiAs at home for 5 days at the conclusion of research house admission. DiAs: DiAs is the central component of our system. It is a standard cell phone running on an Android operating system. The cell phone has been changed to prevent from (1) using it as a phone or browser, (2) changing the volume (3) accidentally shutting it off. The cell phone runs an algorithm and is connected to work with the insulin pump and continuous glucose monitor to help keep the blood sugar in a desired range and	The subject will wear the continuous glucose monitor with the study insulin pump for a full 7 day period (approximately 7 consecutive 24 hour periods). The subject will follow their usual regimen. The subject will be asked to use the bolus calculator function on your insulin pump and enter the carbohydrate information that you eat during the week. Sensor Augmented Pump Therapy: Insulin pump plus CGM.
Measure Participants	40	40
Mean (Standard Deviation) [percentage of time spent in range]	78.3 (10.2)	71.4 (11.6)

2. Secondary Outcome

Title	Overnight Target Range
Description	Assess time spent within target range of 80-140 mg/dl overnight with USS Virginia Closed Loop compared to sensor-augmented pump therapy alone
Time Frame	40 hours

Outcome Measure Data

Analysis Population Description

Cross-over trial for a total of 40 participants

Arm/Group Title	USS Virginia Closed Loop Control	Sensor Augmented Pump Therapy
Arm/Group Description	The subject will be admitted to the research house/hotel and will be discharged after 5 nights. The subject will be trained on DiAs (CLC controller) and on how to respond to the system's alerts. The DiAs will be initiated by 11:00 PM and will be discontinued before breakfast. A limited number of UVA and UPadova subjects will be asked to wear the DiAs at home for 5 days at the conclusion of research house admission.	The subject will wear the continuous glucose monitor with the study insulin pump for a full 7 day period (approximately 7 consecutive 24 hour periods). Sensor Augmented Pump Therapy: Insulin pump plus CGM.
Measure Participants	40	40
Mean (Standard Deviation) [percentage of time overnight]	61.1 (20.6)	39.6 (18.3)

3. Secondary Outcome

Title	Decreased Overnight Hypoglycemia
Description	Assess the effect of USS Virginia Closed Loop System to decrease hypoglycemia overnight compared to sensor-augmented pump therapy alone
Time Frame	40 hours

Outcome Measure Data

Analysis Population Description

Cross-over trial with a total of 40 participants

Arm/Group Title	USS Virginia Closed Loop Control	Sensor Augmented Pump Therapy
Arm/Group Description	The subject will be admitted to the research house/hotel and will be discharged after 5 nights. The subject will be trained on DiAs (CLC controller) and on how to respond to the system's alerts. The DiAs will be initiated by 11:00 PM and will be discontinued before breakfast. A limited number of UVA and UPadova subjects will be asked to wear the DiAs at home for 5 days at the conclusion of research house admission.	The subject will wear the continuous glucose monitor with the study insulin pump for a full 7 day period (approximately 7 consecutive 24 hour periods). Sensor Augmented Pump Therapy: Insulin pump plus CGM.
Measure Participants	40	40
Mean (Standard Deviation) [percentage of time overnight]	0.9 (1.5)	3.2 (3.4)

4. Secondary Outcome

Title	Morning Glucose Levels
Description	Assess the distribution of wake-up glucose levels at 07:00 achieved by USS Virginia Closed Loop vs. to sensor-augmented pump therapy alone;
Time Frame	40 hours

Outcome Measure Data

Analysis Population Description

Cross-over trial with a total of 40 participants

Arm/Group Title	USS Virginia Closed Loop Control	Sensor Augmented Pump Therapy
Arm/Group Description	The subject will be admitted to the research house/hotel and will be discharged after 5 nights. The subject will be trained on DiAs (CLC controller) and on how to respond to the system's alerts. The DiAs will be initiated by 11:00 PM and will be discontinued before breakfast. A limited number of UVA and UPadova subjects will be asked to wear the DiAs at home for 5 days at the conclusion of research house admission.	The subject will wear the continuous glucose monitor with the study insulin pump for a full 7 day period (approximately 7 consecutive 24 hour periods). Sensor Augmented Pump Therapy: Insulin pump plus CGM.
Measure Participants	40	40
Mean (Standard Deviation) [mg/dL]	123.7 (17.8)	145.3 (31.0)

Adverse Events

Time Frame	Approximately 2-3 weeks.
Arm/Group Title	USS Virginia Closed Loop Control and SAP
Arm/Group Description	Combined Group in Cross-Over Trial that had CLC and SAP.
All Cause Mortality
	USS Virginia Closed Loop Control and SAP
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	USS Virginia Closed Loop Control and SAP
	Affected / at Risk (%)	# Events
Total	0/40 (0%)
Other (Not Including Serious) Adverse Events
	USS Virginia Closed Loop Control and SAP
	Affected / at Risk (%)	# Events
Total	1/40 (2.5%)
Ear and labyrinth disorders
Otitis media	1/40 (2.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.