Type 1 Diabetes
Conditions
Keywords
exercise, artificial pancreas, hypoglycemia, type 1 diabetes
Brief summary
The risk of hypoglycemia in individuals with type 1 diabetes increases considerably during exercise. As a result, many patients with type 1 diabetes experience fear of and reluctance to pursue physical activity, in order to avoid the discomforting symptoms associated with hypoglycemia. The bi-hormonal artificial pancreas, a device used for automatic delivery of insulin and glucagon subcutaneously to subjects with type 1 diabetes, is paving the way to revolutionize the management of this disease. The investigator's group has recently completed a study of the bi-hormonal artificial pancreas system during exercise, suggesting reduced hypoglycemia around the exercise period. In order to prepare for a future home study, the ability to detect, grade, and classify physical activity so as to appropriately adjust system parameters is vital in helping to prevent exercise induced hypoglycemia in the home setting. This study is designed to collect 3-axis accelerometry data and heart rate data during a variety of different home activities, as well as during formal exercise in both healthy subjects and subjects with type 1 diabetes. Additionally, the investigators will observe the change in glucose levels before and after exercise in subjects with type 1 diabetes.
Detailed description
The artificial pancreas, a device used for automatic delivery of insulin and glucagon subcutaneously to subjects with type 1 diabetes, is paving the way to revolutionize the management of this disease. Already, the benefit of improved glycemic control compared to current open-loop pump therapy has been demonstrated in several trials. The investigator's group has shown that artificial pancreas algorithm dual hormone system effectively manages blood glucose in a clinic setting and the investigators have specifically shown great progress using glucagon to reduce hypoglycemic episodes outside of exercise. The investigators most recent inpatient study, as yet unpublished, shows that adjusting insulin and glucagon delivery during closed loop treatment, after announcing exercise, effectively reduces mean time below a glucose level of 70 mg/dl when compared to closed loop control without adjustments. The investigators utilized initial open-loop data from this study to help devise dosing changes for the artificial pancreas algorithm. In order to prepare for a future home study, the ability to detect, grade, and classify physical activity so as to appropriately adjust system parameters is vital in helping to prevent exercise induced hypoglycemia in the home setting. Currently, our closed-loop system transmits heart rate and accelerometry outputs from a Zephyrlife BioPatch monitoring device to a Nexus 5 smart phone master controller via Bluetooth. The algorithm then converts the heart rate and accelerometry data into modified estimated energy expenditure - accounting for age, weight, height, sex, resting and sitting heart rates - to determine if exercise is present. However, further data collection is needed to hone the specificity and sensitivity of the detection algorithm to account for a wide variety of subject characteristics and activities. This study is designed to collect 3-axis accelerometry data and heart rate data during a variety of different home activities, as well as during formal exercise, which included aerobic exercise (on a calibrated treadmill) and resistance exercise (straight-leg raises or equivalent) in healthy subjects as well as subjects with type 1 diabetes. Optionally VO2 data from a portable VO2 mask will be obtained. The data collected will be used to further enhance our algorithm that, in future closed-loop studies, will detect exercise and automatically trigger algorithmic adjustments to reduce exercise-related hypoglycemia during and after exercise in individuals with type 1 diabetes.
Interventions
BEHAVIORALAerobic Exercise
Exercise for three 15 minute periods, with 10 minute rests between each period, and exercise intensity will vary between periods to achieve different energy expenditures, which may be determined based on VO2 measurements.
BEHAVIORALResistance Exercise
Subjects will perform 5-15 minutes of up to 7 different activities of daily living, followed by 20 minutes of resistance exercise, such as straight leg raises.
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
TYPE 1 DIABETIC SUBJECT CRITERIA Inclusion criteria: 1. Male or female subjects 21 to 45 years of age with a diagnosis of T1D for at least 6 months on an insulin pump. 2. Physically active on a regular basis, i.e. at least 3 days of scheduled physical activity per week and willing to perform approximately 60 minutes of exercise (as determined by the investigator after reviewing the subjects activity level). 3. Willingness to follow all study procedures. 4. Willingness to sign informed consent and HIPAA documents.
Exclusion criteria
a. Pregnancy or Lactation: i. For women of childbearing potential, there is a requirement for a negative urine pregnancy test. b. Any cardiovascular disease, defined as a clinically significant EKG abnormality at the time of screening or any history of: stroke, heart failure, myocardial infarction, angina pectoris, or coronary arterial bypass graft or angioplasty. Diagnosis of 2nd or 3rd degree heart block or any non-physiological arrhythmia judged by the investigator to be exclusionary. c. Renal insufficiency (GFR \< 60 ml/min, using the MDRD equation as report by the OHSU laboratory). d. Hematocrit of less than or equal to 34%. e. History of severe hypoglycemia during the past 12 months prior to screening visit or hypoglycemia unawareness as judged by the investigator. f. Adrenal insufficiency. g. Any active infection. h. Known or suspected abuse of alcohol, narcotics, or illicit drugs (except marijuana use). i. Seizure disorder. j. Active foot ulceration. k. Severe peripheral arterial disease characterized by ischemic rest pain or severe claudication. l. Major surgical operation within 30 days prior to screening. m. Use of an investigational drug within 30 days prior to screening. n. Chronic usage of any immunosuppressive medication (such as cyclosporine, azathioprine, sirolimus, or tacrolimus). o. Bleeding disorder, treatment with warfarin, or platelet count below 50,000. p. Current administration of oral or parenteral corticosteroids. q. Any life threatening disease, including malignant neoplasms and medical history of malignant neoplasms within the past 5 years prior to screening (except basal and squamous cell skin cancer). r. Any concurrent illness, other than diabetes, that is not controlled by a stable therapeutic regimen. s. Beta blockers or non-dihydropyridine calcium channel blockers. t. A positive response to any of the questions from the Physical Activity Readiness Questionnaire, see Appendix A. u. Any chest discomfort with physical activity, including pain or pressure, or other types of discomfort. v. Any clinically significant disease or disorder which in the opinion of the Investigator may jeopardize the subject's safety or compliance with the protocol. HEALTHY SUBJECT CRITERIA Inclusion Criteria: 1. Male or female subjects 21 to 45 years of age. 2. Physically active on a regular basis, i.e. at least 3 days of scheduled physical activity per week and willing to perform approximately 60 minutes of exercise (as determined by the investigator after reviewing the subjects activity level). 3. Willingness to follow all study procedures. 4. Willingness to sign informed consent and HIPAA documents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Sensor Glucose in Subjects With Type 1 Diabetes | 4 hours | The mean change in sensor glucose before and after both exercise periods (aerobic and resistance) during the study visit, obtained from Dexcom G4 sensors in the subjects with type 1 diabetes. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aerobic First, Resistance Second Subjects will complete three 15 minute periods of aerobic exercise, with 10 minute recovery between each period. This will be followed by 5-15 minute periods of up to 7 activities of daily living with an additional 20 minute period of resistance exercise, such as straight leg raises.
Aerobic Exercise: Exercise for three 15 minute periods, with 10 minute rests between each period, and exercise intensity will vary between periods to achieve different energy expenditures, which may be determined based on VO2 measurements.
Resistance Exercise: Subjects will perform 5-15 minutes of up to 7 different activities of daily living, followed by 20 minutes of resistance exercise, such as straight leg raises. | 24 |
| Resistance First, Aerobic Second Subjects will complete 5-15 minute periods of up to 7 activities of daily living with an additional 20 minute period of resistance exercise, such as straight leg raises. This will be followed by three 15 minute periods of aerobic exercise, with 10 minute recovery between each period.
Aerobic Exercise: Exercise for three 15 minute periods, with 10 minute rests between each period, and exercise intensity will vary between periods to achieve different energy expenditures, which may be determined based on VO2 measurements.
Resistance Exercise: Subjects will perform 5-15 minutes of up to 7 different activities of daily living, followed by 20 minutes of resistance exercise, such as straight leg raises. | 6 |
| Total | 30 |
Baseline characteristics
| Characteristic | Aerobic First, Resistance Second | Resistance First, Aerobic Second | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 6 Participants | 30 Participants |
| Age, Continuous | 31.8 years STANDARD_DEVIATION 6.1 | 31.4 years STANDARD_DEVIATION 4.7 | 31.6 years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 6 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 6 Participants | 27 Participants |
| Sex: Female, Male Female | 14 Participants | 3 Participants | 17 Participants |
| Sex: Female, Male Male | 10 Participants | 3 Participants | 13 Participants |
| Type 1 Diabetes | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Mean Change in Sensor Glucose in Subjects With Type 1 Diabetes
The mean change in sensor glucose before and after both exercise periods (aerobic and resistance) during the study visit, obtained from Dexcom G4 sensors in the subjects with type 1 diabetes.
Time frame: 4 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aerobic Exercise | Mean Change in Sensor Glucose in Subjects With Type 1 Diabetes | -26.4 mg/dL | Standard Deviation 41.1 |
| Resistance Exercise | Mean Change in Sensor Glucose in Subjects With Type 1 Diabetes | 12.0 mg/dL | Standard Deviation 28.5 |