Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01727817
Recruitment Status : Completed
First Posted : November 16, 2012
Last Update Posted : September 30, 2014
Juvenile Diabetes Research Foundation
Sansum Diabetes Research Institute
University Hospital, Montpellier
Information provided by (Responsible Party):
University of Virginia

Tracking Information
First Submitted Date  ICMJE November 8, 2012
First Posted Date  ICMJE November 16, 2012
Last Update Posted Date September 30, 2014
Study Start Date  ICMJE January 2013
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 12, 2012)
Effect size of Control-to-Range (CTR) vs. Continuous Glucose Monitor (CGM)-augmented insulin pump treatment in an outpatient setting. [ Time Frame: 40 hours ]
The investigators expect that compared to CGM-augmented insulin pump treatment, CTR will result in moderate effect size of approximately 0.4, in terms of reduction of the overnight risk for hypoglycemia as measured by the Low Blood Glucose Index computed from retrofitted CGM data. This effect is not expected to be statistically significant with the anticipated sample size but will be used to inform power analysis for the subsequent multi-center trial of CTR at home.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2012)
Time spent in target range [ Time Frame: 40 hours ]
CTR will improve (non-significantly at the projected sample size of N=5 subjects/site) the time spent within the target range of 80-140 mg/dl overnight (computed from retrofitted CGM data) and will reduce the extent of postprandial glucose excursions during the day. These data will provide justification and design support for a subsequent larger multi-center trial of CTR at home.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 12, 2012)
  • Patient comfort with the Diabetes Assistant (DiAs) user interface [ Time Frame: 40 hours ]
    Investigators want to ensure that subjects are comfortable using the cell phone to assess the current status of their diabetes management. Subjects will use the user guide as guidance on how to evaluate the DiAs' hypoglycemia and hyperglycemia warning lights, how to inform DiAs of carbohydrates consumed, and other important diabetes management issues.
  • Reliability of DiAs remote monitoring [ Time Frame: 40 hours ]
    Assess the DiAs remote monitoring by medical personnel/technicians to confirm appropriate functioning outside of the hospital setting.
  • Reliability of inter-device connections between DiAs and the CGM and between DiAs and the insulin pump. [ Time Frame: 40 hours ]
    Assess the functioning of the connections between DiAs, the continuous glucose sensor, and the insulin pump.
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Early Feasibility Study 2 of Outpatient Control-to-Range - Testing System Efficacy (Italy)
Official Title  ICMJE Early Feasibility Study 2 of Outpatient Control-to-Range - Testing System Efficacy
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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 1
Intervention  ICMJE Device: Diabetes Assistant (DiAs)
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.
Study Arms  ICMJE
  • Experimental: Experimental Involving Automated CTR
    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. Subjects 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.
    Intervention: Device: Diabetes Assistant (DiAs)
  • No Intervention: CGM-Augmented Insulin Pump Treatment
    Open Loop Control: Insulin delivery will be controlled by the Diabetes Assistant (DiAs) system running in open-loop mode. Subjects 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. Subjects will be reminded that all treatment decisions should be based on fingerstick values and not on continuous glucose monitor (CGM) values.
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 12, 2012)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2013
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. ≥21 and <65 years old.
  2. 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

  3. Use of an insulin pump to treat his/her diabetes for at least 1 year.
  4. 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.
  5. HbA1c <9% as measured with DCA2000 or equivalent device.
  6. Not currently known to be pregnant, breast feeding, or intending to become pregnant (females).
  7. Demonstration of proper mental status and cognition for the study.
  8. Willingness to avoid consumption of acetaminophen-containing products during the study interventions involving CGM use.
  9. 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.

Exclusion Criteria:

  1. Severe hypoglycemia resulting in seizure, loss of consciousness, or diabetic ketoacidosis within the 12 months prior to enrollment.
  2. Pregnancy; breast feeding, or intention of becoming pregnant.
  3. Uncontrolled arterial hypertension (Resting diastolic blood pressure >90 mmHg and/or systolic blood pressure >160 mmHg).
  4. 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.
  5. Self-reported hypoglycemia unawareness.
  6. History of a systemic or deep tissue infection with methicillin-resistant staph aureus or Candida albicans.
  7. 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).
  8. Anticoagulant therapy other than aspirin.
  9. Oral steroids.
  10. Medical condition requiring use of an acetaminophen-containing medication that cannot be withheld for the study admissions.
  11. Psychiatric disorders that would interfere with study tasks (e.g. inpatient psychiatric treatment within 6 months prior to enrollment).
  12. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.
  13. Known current or recent alcohol or drug abuse.
  14. Medical conditions that would make operating a CGM, the DiAs cell phone or insulin pump difficult (e.g. blindness, severe arthritis, immobility).
  15. 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).
  16. In adherence with the One Touch Ultra 2 User Guide, subjects with hematocrit levels less than 30% and above 55% will be excluded.
  17. Impaired hepatic function measured as alanine aminotransferase or aspartate aminotransferase ≥three times the upper reference limit.
  18. Impaired renal function measured as creatinine >1.2 times above the upper limit of normal.
  19. Uncontrolled microvascular (diabetic) complications, such as current proliferative diabetic retinopathy or macular edema, known diabetic nephropathy (other than microalbuminuria with normal creatinine) or neuropathy requiring treatment.
  20. Active gastroparesis requiring current medical therapy.
  21. 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.
  22. Uncontrolled thyroid disease.
  23. Known bleeding diathesis or dyscrasia.
  24. Known allergy to medical adhesives, components of the insulin pump insertion set or continuous glucose monitor sensor.
  25. Active enrollment in another clinical trial.
  26. Use of anti-diabetic agents other than continuous subcutaneous insulin infusion (CSII) including long-acting insulin, intermediate-acting insulin, metformin, sulfonylureas, meglitinides, thiazolidinediones, DPP-IV inhibitors, glucagon-like peptide 1 agonists, and alpha-glucosidase inhibitors
  27. Subjects with basal rates less than 0.01U/hr.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01727817
Other Study ID Numbers  ICMJE 0052904
JDRF 22-2011-649 ( Other Grant/Funding Number: Juvenile Diabetes Research Foundation )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Virginia
Study Sponsor  ICMJE University of Virginia
Collaborators  ICMJE
  • Juvenile Diabetes Research Foundation
  • Sansum Diabetes Research Institute
  • University Hospital, Montpellier
Investigators  ICMJE
Principal Investigator: Claudio Cobelli, Ph.D. University of Padova
Study Director: Boris P. Kovatchev, Ph.D. University of Virginia
PRS Account University of Virginia
Verification Date September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP