Clinical trial NCT01945060: Closed Loop Control in Adolescents Using Heart Rate as Exercise Indicator
Official title: Closed Loop Control in Adolescents Using Heart Rate as Exercise Indicator
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Keywords: Artificial Pancreas Project
Diabetes Assistant (DiAs) Medical Platform System
Artificial Pancreas Platform
Insulin Pump
Continuous Glucose Monitor
Closed-Loop Control
heart rate Control to Range System (hrCTR)
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: Virginia Commonwealth University
name: DexCom, Inc.
name: Tandem Diabetes Care, Inc.
First posted: 2013-09-18
Enrollment: 22
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The purpose of this study is to see if the Artificial Pancreas (AP) Platform can successfully control blood sugar in people with type 1 diabetes mellitus on insulin pump therapy in a hospital setting. Investigators will also be studying to see if the heart rate informed Control To Range (hrCTR) can improve the performance of the system during and immediately after exercise.

Detailed description: The artificial pancreas (AP), known as Closed-Loop Control of blood glucose in diabetes, is a system combining a continuous glucose monitor (glucose sensor), a control algorithm (complex mathematical formulas), and an insulin pump. The algorithms are intended to maintain your blood glucose level within a certain range. This is called Control-to-Range. The algorithms are intended to maintain your blood glucose level within a certain range. The algorithms run on a portable AP platform on an Android smart phone, called the Diabetes Assistant (DiAs) Medical Platform.

In this study, researchers hypothesize that the heart rate informed Control To Range (hrCTR) will limit the risk for hypo and hyperglycemia during and immediately after exercise in adolescents 12 - 17 years of age and assess if the hrCTR will improve additional measures of overall short term glycemic control in this population.

This trial will be performed at both Virginia Commonwealth University and the University of Virginia. IRB approvals have been obtained at both institutions.

Eligibility criteria: Inclusion Criteria:

1. 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
   * Hemoglobin A1c (HbA1c) ≥ 6.5% documented - confirmed
   * Random glucose ≥ 200 mg/dL with symptoms
   * No data are available from the time of diagnosis but the participant has a convincing history of medical care and biochemical parameters consistent with T1DM
2. Criteria for requiring insulin at diagnosis (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 eventually require insulin that has been used continually
3. Criteria for Type 1 Diabetes Mellitus (T1DM) (at least 1 must be met):

   * Documented low or absent C-peptide level.
   * Documented presence of islet cell autoantibodies (ICA) or glutamic acid decarboxylase (GAD65) autoantibodies.
   * No data are available from the time of diagnosis but the participant has a convincing history of medical care and biochemical parameters consistent with T1DM

In addition, all subjects will meet the following additional criteria:

* Use an insulin pump (CSII) to treat his/her diabetes for at least 6 months
* Actively use a bolus calculator with the current insulin pump with pre-defined parameters for carbohydrate (CHO) ratio, insulin sensitivity factor (ISF), and target glucose
* Current HbA1c between 5.0% and 10.5% 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 while wearing the continuous glucose monitor sensor.

Exclusion Criteria:

* Clinical diagnosis of Type 2 Diabetes Mellitus (T2DM)
* Diabetic ketoacidosis within 6 months prior to enrollment
* Severe hypoglycemia resulting in seizure or loss of consciousness within 3 months prior to enrollment
* Pregnancy, breast feeding, or intention to become pregnant
* Subjects weighing less than 40 kg
* Hematocrit \<36% (females); \<38% (males)
* Conditions which may increase the risk of hypoglycemia such as known history of cerebrovascular event, history of arrhythmias, seizure disorder, syncope, adrenal insufficiency, or neurologic disease
* Additional conditions which may inhibit the ability to perform exercise (e.g. injury to or immobility of limbs, neuromuscular disease, exercise-induced asthma requiring inhaler use within the last 12 months or clinically impaired pulmonary function)
* 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)
* 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 continuous glucose monitor (implantable cardioverter defibrillator, electronic pacemaker, neurostimulator, intrathecal pump, and cochlear implants)
* Medical condition requiring use of an acetaminophen-containing medication that cannot be withheld for the study admission.
* Psychiatric disorders that would interfere with study tasks (e.g. inpatient psychiatric treatment within 6 months prior to enrollment, uncontrolled anxiety or panic disorder)
* Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation
* Medical conditions that would make operating a continuous glucose monitor, 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)
* Known micro vascular (diabetic) complications (other than diabetic non-proliferative retinopathy), such as history of laser coagulation, proliferative diabetic retinopathy, known diabetic nephropathy (other than microalbuminuria with normal creatinine) or neuropathy requiring treatment
* Active gastroparesis requiring current medical therapy
* If on antihypertensive, thyroid, or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study
* Known bleeding diathesis or dyscrasia
* Allergy to medical adhesives, components of the insulin pump insertion set or continuous glucose monitor sensor
* Anticoagulant therapy other than aspirin
* Oral steroids
* Active enrollment in another clinical trial
* Unwillingness to avoid acetaminophen while wearing the continuous glucose monitor sensor.
* Unwillingness to withhold dietary supplements two weeks prior to and during admission
* Unwillingness to use an approved form of birth control during this study by a sexually active female participant.
* Subject develops a febrile illness within 24 hours of inpatient admission.

Primary outcomes:
measure: Low Blood Glucose Index (LBGI)
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Center for Diabetes Technology
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Gary Francis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Marc Breton, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: DeBoer MD, Chernavvsky DR, Topchyan K, Kovatchev BP, Francis GL, Breton MD. Heart rate informed artificial pancreas system enhances glycemic control during exercise in adolescents with T1D. Pediatr Diabetes. 2017 Nov;18(7):540-546. doi: 10.1111/pedi.12454. Epub 2016 Oct 13.