Real-time Adaptation to Changes in Insulin Sensitivity
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin Resistance
Intervention: The Fading Memory Proportional Derivative/Adaptive Proportional Derivative Algorithm; The Adaptive Proportional Derivative Algorithm
Intervention description: The APD algorithm is based largely on a program that employs the Fading Memory Proportional Derivative (FMPD) insulin and glucagon infusion algorithm. The FMPD algorithm determines insulin and glucagon delivery rates based on proportional error, defined as the difference between the current glucose level and the target level, and the derivative error, defined as the rate of change of the glucose. The "fading memory" designation refers to weighting recent errors more heavily than remote errors.
The APD algorithm, like the FMPD algorithm, will determine insulin and glucagon infusion rates based on sensed glucose values and utilizes the derivative and proportional glucose error to determine delivery rates of insulin. However, the APD algorithm has a model predictive element which also leads to frequent measurement of tissue sensitivity to insulin.; The APD algorithm is based largely on a program that employs the Fading Memory Proportional Derivative (FMPD) insulin and glucagon infusion algorithm. The FMPD algorithm determines insulin and glucagon delivery rates based on proportional error, defined as the difference between the current glucose level and the target level, and the derivative error, defined as the rate of change of the glucose. The "fading memory" designation refers to weighting recent errors more heavily than remote errors.
The APD algorithm, like the FMPD algorithm, will determine insulin and glucagon infusion rates based on sensed glucose values and utilizes the derivative and proportional glucose error to determine delivery rates of insulin. However, the APD algorithm has a model predictive element which also leads to frequent measurement of tissue sensitivity to insulin.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Enrollment: 14.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: glucose sensors; artificial pancreas; Diabetes Mellitus

Summary:

      The purpose of this research study is to test an automated blood glucose control system that
      includes a new component designed to adapt to stress. The importance of this component is
      that when Type 1 Diabetics are stressed (for example, from illness or infection), their body
      is resistant to the effects of insulin. The investigators will be adjusting their blood
      glucose using insulin and glucagon and making their body less sensitive to insulin with a
      steroid, hydrocortisone. Insulin is a hormone that lowers blood glucose. Glucagon raises
      blood glucose when it is low. Both are natural hormones made by people without diabetes.
      Hydrocortisone is a steroid that will increase their blood glucose temporarily and will be
      given every 4 hours. All subjects will participate in two 33 hour experiments. One experiment
      will use the adaptive version of the sensor-based glucose control system. The other study
      will use the original version of the control system, without the adaptive component, for the
      first 13 hours. Then, the adaptive component will be added to the glucose control system for
      the remaining 20 hours of the study. Our primary goal is to assess the effectiveness of the
      adaptive component to control glucose levels in the presence of steroid-induced insulin
      resistance in persons with Type 1 Diabetes Mellitus.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of Type 1 Diabetes Mellitus for at least 1 year

          -  Male or Female subjects 21 to 65 years of age

          -  Willingness to follow all study procedures, including attending all clinic visits

          -  Willingness to sign informed consent and HIPAA documents.

        Exclusion Criteria:

          -  Pregnancy or Lactation: For women of childbearing potential: there is a requirement
             for a negative urine pregnancy test and for agreement to use contraception during the
             study and for at least 1 month after participating in the study. Acceptable
             contraception includes birth control pill / patch / vaginal ring, Depo-Provera,
             Norplant, an IUD, the double barrier method (the woman uses a diaphragm and spermicide
             and the man uses a condom), or abstinence.

          -  Renal insufficiency (serum creatinine of 2.0 mg/dL or greater).

          -  Serum ALT or AST equal to or greater than 3 times the upper limit of normal; hepatic
             synthetic insufficiency as defined as a serum albumin of less than 3.3 g/dL; or serum
             bilirubin of over 2.

          -  Adrenal insufficiency

          -  Hematocrit of less than or equal to 34%.

          -  A history of cerebrovascular disease or coronary artery disease regardless of the time
             since occurrence.

          -  Congestive heart failure, NYHA class III or IV.

          -  Cardiac rhythm disturbance characterized by: 2nd or 3rd degree heart block,
             bradycardia of less than 50 bpm (exception of bradycardia in an aerobic athlete),
             tachycardia of greater than 100 bpm, or any arrhythmia judged by the investigator to
             be exclusionary.

          -  Any active infection.

          -  Visual impairment preventing reading of glucose meter values or continuous glucose
             monitoring device.

          -  Physical impairment impeding the ability to use a glucose meter or glucose monitoring
             device.

          -  Active foot ulceration.

          -  Severe peripheral arterial disease characterized by ischemic rest pain or severe
             claudication.

          -  Active alcohol abuse, substance abuse, or severe mental illness (as judged by the
             principal investigator).

          -  Active malignancy, except basal cell or squamous cell skin cancers.

          -  Major surgical operation within 30 days prior to screening.

          -  Seizure disorder.

          -  Any concurrent illness, other than diabetes, that is not controlled by a stable
             therapeutic regimen.

          -  Chronic usage of any immunosuppressive medication (such as cyclosporine, azathioprine,
             sirolimus, or tacrolimus).

          -  Current administration of oral or parenteral corticosteroids.

          -  Use of an investigational drug within 30 days prior to screening.

          -  Bleeding disorder, treatment with warfarin, or platelet count below 50,000.

          -  History of major non-compliance.

          -  Allergy to aspart insulin.

          -  Allergy to glucagon.

          -  Past history of pheochromocytoma or a family history of MEN 2, neurofibromatosis, or
             von Hippel-Lindau disease.

          -  Insulin resistance requiring more than 200 units per day.

          -  Need for uninterrupted treatment of acetaminophen.

          -  Intolerance of mild hypoglycemia (glucose 60-70 mg/dl).

          -  Patients using all dietary supplements (except for vitamin supplements, calcium or
             vitamin D in standard doses).

          -  Patients with a history of glaucoma or who have not had an ophthalmologic exam in the
             previous 2 years (because of the risk of increased intraocular pressure)

          -  Patients with a history of psychiatric disease or steroid-induced psychosis.

          -  Patients currently on estrogen supplementation (low dose estrogen contraceptives are
             not exclusionary).

          -  Chronic use of dietary supplements that contain adrenal cell extracts, adrenal
             cortical extracts, or other hormones.

          -  The use of dietary supplements (except for vitamin supplements, calcium or vitamin D
             in standard doses) will be exclusionary (unless the subjects agrees to abstain from
             taking such supplements for three weeks before beginning the study.

          -  Administration of an immunization (such as a flu or travel immunization) or plans to
             receive such an immunization within one week of beginning of the study.

          -  Any reason the principal investigator deems exclusionary.