Type 1 Diabetes Mellitus
Conditions
Brief summary
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.
Interventions
DEVICEOpen-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...).
DEVICEClosed-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.
Sponsors
Abbott Diabetes Care
DexCom, Inc.
Insulet Corporation
University of California, Santa Barbara
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycemic Events | 22 hours | 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Time in Euglycemia | 22 hours | Percent of time the patient plasma glucose as measured by YSI is between 70mg/dl and 180mg/dl |
| Mean Glucose | 22 hours | Average plasma glucose concentration in mg/dl |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adolescents Adolescents participated in both the Standard Control to Range (sCTR) Closed-Loop Control (CLC) Admission and the Open-Loop admission.
Experimental: The CLC used a computer to make recommendations for their insulin treatment. This system was designed to both:
1. 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;
2. predict and avoid hypoglycemic events, based on continuous glucose reading and past insulin injection.
Placebo Comparator: Open Loop. The subjects were in charge of their insulin treatment. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Adolescents |
|---|---|
| Age, Continuous | 14.5 years STANDARD_DEVIATION 1.5 |
| HbA1c | 8.6 percent STANDARD_DEVIATION 0.8 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
Hypoglycemic Events
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
Time frame: 22 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Closed-Loop Control (CLC) | Hypoglycemic Events | Overall (t=22h) | 0.27 events/patient | Standard Error 0.19 |
| Closed-Loop Control (CLC) | Hypoglycemic Events | Recovery (t=1h) | 0 events/patient | Standard Error 0 |
| Closed-Loop Control (CLC) | Hypoglycemic Events | Exercise (t=0.5h) | 0.18 events/patient | Standard Error 0.12 |
| Closed-Loop Control (CLC) | Hypoglycemic Events | Overnight (t=7h) | 0 events/patient | Standard Error 0 |
| Open-Loop | Hypoglycemic Events | Exercise (t=0.5h) | 0.18 events/patient | Standard Error 0.12 |
| Open-Loop | Hypoglycemic Events | Overall (t=22h) | 1.0 events/patient | Standard Error 0.5 |
| Open-Loop | Hypoglycemic Events | Overnight (t=7h) | 0.18 events/patient | Standard Error 0.18 |
| Open-Loop | Hypoglycemic Events | Recovery (t=1h) | 0.18 events/patient | Standard Error 0.12 |
Secondary
Mean Glucose
Average plasma glucose concentration in mg/dl
Time frame: 22 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Closed-Loop Control (CLC) | Mean Glucose | Overall (t=22h) | 166.24 mg/dL | Standard Error 7.23 |
| Closed-Loop Control (CLC) | Mean Glucose | Day (t=15h) | 155.44 mg/dL | Standard Error 7.76 |
| Closed-Loop Control (CLC) | Mean Glucose | Night (t=7) | 177.29 mg/dL | Standard Error 8.23 |
| Open-Loop | Mean Glucose | Overall (t=22h) | 176.1 mg/dL | Standard Error 18.04 |
| Open-Loop | Mean Glucose | Day (t=15h) | 160.57 mg/dL | Standard Error 16.54 |
| Open-Loop | Mean Glucose | Night (t=7) | 193.04 mg/dL | Standard Error 22.08 |
Secondary
Percent Time in Euglycemia
Percent of time the patient plasma glucose as measured by YSI is between 70mg/dl and 180mg/dl
Time frame: 22 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Closed-Loop Control (CLC) | Percent Time in Euglycemia | Overall (t=22h) | 65.1 percentage of time in range | Standard Error 6.8 |
| Closed-Loop Control (CLC) | Percent Time in Euglycemia | Night (t=7h) | 56.0 percentage of time in range | Standard Error 11.8 |
| Closed-Loop Control (CLC) | Percent Time in Euglycemia | Day (t=15h) | 74.0 percentage of time in range | Standard Error 5.2 |
| Open-Loop | Percent Time in Euglycemia | Overall (t=22h) | 50.2 percentage of time in range | Standard Error 9.7 |
| Open-Loop | Percent Time in Euglycemia | Night (t=7h) | 43.6 percentage of time in range | Standard Error 13.3 |
| Open-Loop | Percent Time in Euglycemia | Day (t=15h) | 57.0 percentage of time in range | Standard Error 8.9 |