Hypoglycemia Prevention After Exercise in Adolescent T1DM Patients Using a Control to Range System (MDB005)

This study has been completed.
Sponsor:
Collaborators:
Abbott Diabetes Care
DexCom, Inc.
Insulet Corporation
University of California, Santa Barbara
Information provided by (Responsible Party):
Marc Breton, University of Virginia
ClinicalTrials.gov Identifier:
NCT01390259
First received: July 6, 2011
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

In this protocol the investigators plan to demonstrate management of glucose using a modular insulin management system based on continuous glucose monitoring and targeted towards the avoidance of hypoglycemic and prolonged hyperglycemic episodes (i.e. control to range). The protocol is designed to challenge the insulin management system with meals and mild exercise, so as to demonstrate its capacity to avoid large glucose excursion with changing metabolic state. This system is designed to both

  • monitor the meal boluses of the patient and correct it in case of observed/predicted under insulinization (avoidance of prolonged hyperglycemia), based on a coarse and subjective knowledge of the meal amount, a precise understanding of the subject's day to day insulin treatment, continuous glucose monitoring, and past insulin injections;
  • predict and avoid hypoglycemic events, based on continuous glucose reading and past insulin injection.

The investigators plan to enroll 12 adolescent T1DM patients (expected retention 10/12) and compare glucose control performances under two treatments: standard vs. the new insulin management system. The protocol will include a total of 5 admissions per subject (3 out-patients and 2 in-patients): screening, CGM insertion 1, CGM insertion 2, inpatient 1 and inpatient 2. During the 24h inpatient admissions the patients will be challenged with 30 minutes of mild exercise and 3 meals, insulin coverage of these events will vary depending on the chosen treatment, each subject will be exposed to both studied treatments (repeated measure design). The order of treatment during the inpatient admissions will be randomized.


Condition Intervention
Type 1 Diabetes Mellitus
Device: Open-Loop
Device: Closed-Loop

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Hypoglycemia Prevention After Exercise in Adolescent T1DM Patients Using a Control to Range System

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Hypoglycemic Events [ Time Frame: 22 hours ] [ Designated as safety issue: Yes ]

    Number of hypoglycemic events below 70 mg/dL per patient per day

    Hypoglycemic event is defined as consecutive YSI plasma glucose measurements below 70 or moderate hypoglycemic symptoms



Secondary Outcome Measures:
  • Percent Time in Euglycemia [ Time Frame: 22 hours ] [ Designated as safety issue: No ]
    Percent of time the patient plasma glucose as measured by YSI is between 70mg/dl and 180mg/dl

  • Mean Glucose [ Time Frame: 22 hours ] [ Designated as safety issue: No ]
    Average plasma glucose concentration in mg/dl


Enrollment: 11
Study Start Date: January 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Closed Loop Control (CLC)

The CLC used a computer to make recommendations for their insulin treatment. This study arm was designed to demonstrate management of glucose using a modular insulin management system based on continuous glucose monitoring and targeted towards the avoidance of hypoglycemic and prolonged hyperglycemic episodes (i.e. control to range). This system was designed to both:

  • monitor the meal boluses of the patient and correct it in case of observed/predicted under insulinization (avoidance of prolonged hyperglycemia), based on a coarse and subjective knowledge of the meal amount, a precise understanding of the subject's day to day insulin treatment, continuous glucose monitoring, and past insulin injections;
  • predict and avoid hypoglycemic events, based on continuous glucose reading and past insulin injection.
Device: Closed-Loop
In this study, the researchers compared the management of diabetes during physical activity and meals with the closed-loop system developed at the University of Virginia. This system uses two DexComTM Seven Continuous Glucose Monitor, a computer containing an investigational control algorithm (well-defined instructions that are expressed in mathematical equations), and an OmniPod Insulin Management System, a portable subcutaneous (under the skin) insulin pump. During the closed-loop admission, the computer based algorithm used CGM values to make recommendations of insulin treatment. The study included a challenge to the insulin management system with meals and mild exercise, so as to demonstrate its capacity to avoid large glucose excursion with changing metabolic state.
Placebo Comparator: Open Loop
The subject were in charge of their insulin treatment.
Device: Open-Loop
This admission was to assess the subjects' level of glucose control and created a base to compare the performance of the closed-loop system. Subjects monitored their own blood glucose values and administer their basal/bolus as they would at home. Otherwise, the admission remained the same as in the closed-loop admission (i.e. meals, exercise, etc...).

  Eligibility

Ages Eligible for Study:   12 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 12 years of age and up to and including 18 years of age.
  • Have type 1 diabetes mellitus as defined by American Diabetes Association criteria or judgment of physician for at least 1 year (including those who may also be treated with metformin).
  • Use of an insulin pump
  • 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
  • Willingness to use lispro (Humalog) insulin for the duration of the inpatient study
  • Demonstration of proper mental status and cognition for the study
  • Willingness to stop using any dietary supplements for two weeks prior to admission and for the duration of their participation
  • HemoglobinA1c < 10.0
  • A score of 2 or greater on the hypoglycemia unawareness scale, see Attachment A
  • Tanner Stage II or greater (not pre-pubertal) on screening physical exam
  • Body weight of 30 kg or more at screening
  • BMI must be under 95th percentile for age based on published BMI reference standards

Exclusion Criteria:

  • Age <12 or >18
  • Pregnancy
  • Hematocrit <37% (females); <36% (males)
  • HemoglobinA1c ≥ 10.0
  • Any symptomatic coronary artery disease, or a history of congenital heart abnormalities.
  • Score of less than 2 on the hypoglycemia unawareness scale
  • Tanner Stage I on screening physical exam
  • Use of a medication that significantly lowers heart rate (beta blockers, reserpine, guanethidine, methyldopa, clonidine, cimetidine, digitalis, calcium channel blockers, amiodarone, antiarrythmic drugs, or lithium)
  • Congestive heart failure
  • History of a cerebrovascular event
  • Use of a medication that significantly impacts glucose metabolism (oral steroids)
  • Atrial fibrillation
  • Uncontrolled hypertension (resting blood pressure >140/90)
  • 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 FreeStyle NavigatorTM CGM or DexCom Seven® (implantable cardioverter-defibrillator, electronic pacemaker, neurostimulator, intrathecal pump, and cochlear implants)
  • Active enrollment in another clinical trial
  • Allergy or adverse reaction to lispro insulin
  • Known adrenal gland problem, pancreatic tumor, or insulinoma
  • Current alcohol abuse by patient history, substance abuse by patient history, or severe mental illness
  • Retinopathy and renal failure
  • Uncontrolled anxiety or panic disorder
  • Known bleeding diathesis or dyscrasia
  • Renal insufficiency (creatinine >1.5)
  • Any comorbid condition affecting glucose metabolism
  • Body weight of less than 30 kg at screening
  • BMI equal to or greater than 95th percentile for age based on published BMI reference standards. See Appendix B.
  • Asthma or exercise -induced asthma
  • Any mobility-restrictive condition
  • Children who are wards of state or at high risk for becoming wards of state
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01390259

Locations
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Virginia
Abbott Diabetes Care
DexCom, Inc.
Insulet Corporation
University of California, Santa Barbara
Investigators
Principal Investigator: Marc D. Breton, Ph.D. University of Virginia, Center for Diabetes Technology
  More Information

Publications:
Responsible Party: Marc Breton, Associate Professor, University of Virginia
ClinicalTrials.gov Identifier: NCT01390259     History of Changes
Other Study ID Numbers: 14758
Study First Received: July 6, 2011
Results First Received: June 27, 2014
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 22, 2014