Early Feasibility Study 2 of Outpatient Control-to-Range - Testing System Efficacy

NCT01714505 | Completed Results

• 2 other identifiers: 16457JDRF 22-2011-649
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

An unblinded, randomized, cross-over design with each patient participating in two 40-hour outpatient admissions: (a) Experimental involving automated Control-to-Range (CTR) and (b) Control using Continuous Glucose Monitor (CGM)- augmented insulin pump treatment outside of a hospital based clinical research center. The principal goal is to validate a smart phone-based control-to-range (CTR) system for ambulatory use and to estimate the effect of CTR vs. sensor-augmented pump therapy, thereby providing justification for further larger home-based trials of CTR.

Conditions

Diabetes Mellitus, Type 1

Keywords

Diabetes Mellitus, Type 1; Continuous Glucose Monitor; Artificial Pancreas; Insulin Pump; Closed Loop control; Open Loop treatment

Outcome Measures

Primary Outcomes (2)

• Safety, Low Blood Glucose Index (LBGI)

  The LBGI reflects the frequency and extent of hypoglycemic episodes and presents the results in "risk space." Thus the LBGI is a weighted average of the number of hypoglycemic readings, with progressively increasing weights as BG levels go down. The increase of the weights follows a risk function; thus the LBGI has been associated with risk for hypoglycemia and prediction of severe hypoglycemic episodes. LBGI \< 2.5 is associated with low risk of hypoglycemia, 2.5 \< LBGI \< 5 is associated with a moderate risk of hypoglycemia and LBGI \> 5 is associated with a high risk of hypoglycemia.

  40 hours (x2 admissions)

• Safety, Frequency of Hypoglycemia

  Hypoglycemic episodes are defined as BG \< 3.9mmol/L

  40 hours (x 2 admissions)

Secondary Outcomes (1)

• Efficacy, Time Spent in Target Range

  40 hours (x2 admissions)

Study Arms (2)

Experimental Involving Automated CTR

EXPERIMENTAL

Closed-Loop Control: Insulin delivery will be controlled by the Diabetes Assistant (DiAs) system running in Control to Range (CTR) or in Safety Only mode. The subject will interact with the system through its Graphic User Interface (GUI). Subjects will not be allowed to administer correction boluses between meals and snacks as the DiAs will automatically be adjusting insulin to correct for hyperglycemia. The total doses recommended by the DiAs prior to meals and snacks includes the correction dose and Insulin on Board (IOB) calculated by the system.

Device: Diabetes Assistant (DiAs)

CGM-Augmented Insulin Pump Treatment

NO INTERVENTION

Open Loop Control: Insulin delivery will be controlled by the Diabetes Assistant (DiAs) system running in open-loop mode. The subject will interact with the system through its Graphic User Interface (GUI). Subjects will be permitted to administer correction boluses at any time during the Control Admission, whether or not they are eating a scheduled meal or snack. DiAs will be initialized with the subject's typical insulin pump settings. The subject will be reminded that all treatment decisions should be based on fingerstick values and not on continuous glucose monitor (CGM) values.

Interventions

Diabetes Assistant (DiAs) DEVICE

A medical platform that uses a smart-phone to connect to a continuous glucose sensor to insulin pump and run closed-loop control. The cell phone runs the Control to Range and is connected to work with the insulin pump and continuous glucose monitor to help keep the blood sugar in a desired range (80-180 mg/dL during the day) and help avoid hypoglycemia during the night.

Experimental Involving Automated CTR

Eligibility Criteria

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

You may qualify if:

• ≥21 and \<65 years old.
• Clinical diagnosis of type 1 diabetes mellitus. For an individual to be enrolled at least one criterion from each list must be met.
• o Criteria for documented hyperglycemia (at least 1 must be met): i. Fasting glucose ≥126 mg/dL - confirmed ii. Two-hour Oral Glucose Tolerance Test (OGTT) glucose ≥200 mg/dL - confirmed iii. HbA1c ≥6.5% documented - confirmed 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
• o 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
• Use of an insulin pump to treat his/her diabetes for at least 1 year.
• Familiarity with a bolus calculator with the current insulin pump with pre-defined parameters for carbohydrate (CHO) ratio, insulin sensitivity factor (ISF), target glucose and active insulin.
• HbA1c \<9% as measured with DCA2000 or equivalent device.
• Not currently known to be pregnant, breast feeding, or intending to become pregnant (females).
• Demonstration of proper mental status and cognition for the study.
• Willingness to avoid consumption of acetaminophen-containing products during the study interventions involving CGM use.
• If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, have stability on the medication for at least 2 months prior to enrollment in the study.

You may not qualify if:

• Severe hypoglycemia resulting in seizure, loss of consciousness, or diabetic ketoacidosis within the 12 months prior to enrollment.
• Pregnancy; breast feeding, or intention of becoming pregnant.
• Uncontrolled arterial hypertension (Resting diastolic blood pressure \>90 mmHg and/or systolic blood pressure \>160 mmHg).
• Conditions which may increase the risks associated with possible hypoglycemia, such as any active cardiac disorder/arrhythmia, uncontrolled coronary artery disease during the previous year (e.g. history of myocardial infarction, acute coronary syndrome, therapeutic coronary intervention, coronary bypass or stenting procedure, stable or unstable angina, episode of chest pain of cardiac etiology with documented EKG changes, or positive stress test or catheterization with coronary blockages \>50%), congestive heart failure, history of cerebrovascular event, seizure disorder, syncope, adrenal insufficiency, neurologic disease or atrial fibrillation.
• Self-reported hypoglycemia unawareness.
• History of a systemic or deep tissue infection with methicillin-resistant staph aureus or Candida albicans.
• Use of a device that may pose electromagnetic compatibility issues and/or radiofrequency interference with the CGM (implantable cardioverter-defibrillator, electronic pacemaker, neurostimulator, intrathecal pump, and cochlear implants).
• Anticoagulant therapy other than aspirin.
• Oral steroids.
• Medical condition requiring use of an acetaminophen-containing medication that cannot be withheld for the study admissions.
• Psychiatric disorders that would interfere with study tasks (e.g. inpatient psychiatric treatment within 6 months prior to enrollment).
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.
• Known current or recent alcohol or drug abuse.
• Medical conditions that would make operating a CGM, the DiAs cell phone or insulin pump difficult (e.g. blindness, severe arthritis, immobility).
• Any skin condition that prevents sensor or pump placement on the abdomen or arm (e.g. bad sunburn, pre-existing dermatitis, intertrigo, psoriasis, extensive scarring, cellulitis).

Sponsors & Collaborators

• University of Virginia: lead
• Juvenile Diabetes Research Foundation: collaborator
• Sansum Diabetes Research Institute: collaborator
• University of Padova: collaborator
• University Hospital, Montpellier: collaborator

Study Sites (2)

Sansum Diabetes Research Institute

Santa Barbara, California, 93105, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Kovatchev BP, Renard E, Cobelli C, Zisser HC, Keith-Hynes P, Anderson SM, Brown SA, Chernavvsky DR, Breton MD, Mize LB, Farret A, Place J, Bruttomesso D, Del Favero S, Boscari F, Galasso S, Avogaro A, Magni L, Di Palma F, Toffanin C, Messori M, Dassau E, Doyle FJ 3rd. Safety of outpatient closed-loop control: first randomized crossover trials of a wearable artificial pancreas. Diabetes Care. 2014 Jul;37(7):1789-96. doi: 10.2337/dc13-2076. Epub 2014 Jun 14.

  PMID: 24929429 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Boris Kovatchev, PhD
• Organization: University of Virginia

boris@virginia.edu

434-924-5592

Study Officials

• Boris P. Kovatchev, Ph.D.

  University of Virginia

  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: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, UVA Center for Diabetes Technology

Study Record Dates

• First Submitted: October 23, 2012
• First Posted: October 26, 2012
• Study Start: October 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: September 9, 2014
• Results First Posted: September 9, 2014

Record last verified: 2014-08

Locations

US (2)