Accelerometer Use in the Prevention of Exercise-Associated Hypoglycemia in Type 1 Diabetes: Outpatient Exercise Protocol

Study Overview
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Brief Summary
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Manually suspending an insulin pump at the beginning of aerobic exercise reduces the risk of exercise-associated hypoglycemia (low blood sugar) in patients with type 1 diabetes (T1D). However, since patients with T1D often do not make exercise-related adjustments to their insulin regimen, our group has developed an algorithm to initiate pump suspension in a user-independent manner upon projecting exercise-associated hypoglycemia. The current study seeks to test the efficacy of this algorithm by asking users to participate in a sports camp while wearing an insulin pump, continuous glucose monitor, and accelerometer/heart rate monitor (to detect exercise), which will communicate electronically to a pump shutoff algorithm. On one of the days the algorithm will be used, while on the other day their normal insulin rate will continue for comparative purposes. The investigators hypothesize that the use of an accelerometer-augmented computer algorithm for insulin pump suspension during exercise will result in significantly fewer episodes of hypoglycemia (both during exercise and in post-exercise monitoring) than in exercise without a pump suspension algorithm.

Detailed Description
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Regular aerobic exercise confers a plethora of health benefits to all individuals and is considered an essential component of the management of type 1 diabetes (T1D) [1]. However, in contrast to non-diabetic subjects - in whom the increased muscle energy requirement during exercise leads to suppression of endogenous insulin secretion - patients with T1D are dependent upon exogenous insulin and are thus at risk for exercise-associated hypoglycemia [1]. Exercise-associated hypoglycemia is the most frequently reported adverse event related to exercise in diabetes [2] and hypoglycemia can occur during exercise or several hours afterwards [3,4]. Although previous research has shown that pre-meal dose reduction of subcutaneous insulin can be effective at decreasing the incidence of exercise-associated hypoglycemia [5], patients with T1D often do not perform such adjustments [6,7]. In contrast to subcutaneous insulin injections, which are reliant upon the patient or caretaker to determine dosage, the insulin pump provides a unique opportunity to avoid hypoglycemia via user-independent, computer-based algorithms for determining insulin delivery. Previous research conducted here at Stanford has demonstrated that algorithms based on continuous glucose monitor (CGM) data can prevent hypoglycemia in the sedentary setting by inducing insulin pump suspension [8-10]. In addition, a study of children and adolescents conducted at Stanford (as a center in the DirecNet group) demonstrated that suspending an insulin pump at the beginning of a period of moderate aerobic exercise reduces the risk of hypoglycemia during that exercise period and subsequently overnight [11]. Thus, by utilizing exercise-detecting accelerometers and an algorithm to initiate pump suspension during exercise, it is likely possible that people with diabetes could avoid exercise-associated hypoglycemia even if they failed to manually alter their pump settings. However, to date, no published studies have utilized accelerometer-derived data in an insulin pump suspension algorithm during exercise. Accelerometers are light-weight motion-sensing devices that can be worn to provide information about the intensity and duration of physical activity [12]. They are small, inexpensive, and could easily be incorporated into current sensors and patch pumps. They can also be used independently or combined with a heart rate monitor (HRM) [13], although most commercially available HRMs currently require a chest strap that can be uncomfortable to wear. Previous studies evaluating the effect of physical activity on insulin sensitivity have utilized accelerometers (worn on a belt at the small of the back, the right side of the trunk in the mid-axillary line, or the left side of the chest) with and without HRMs for activity recognition during subjects' everyday lives. These data were used to classify activity as sedentary, light, moderate, or vigorous based on acceleration signal counts measured over one-minute intervals [13-17]. One study investigated four different accelerometers in a clinical research setting and found each to be very accurate in assessing the intensity of physical activity, regardless of subjects' body habitus [18]. Thus, these devices can provide a reliable means by which the onset, duration, and intensity of exercise can be recognized and reported in real-time to the other components of an artificial pancreas. When combined with CGM and insulin delivery data, this exercise information is a valuable tool in designing an algorithm to decrease or stop insulin delivery in order to decrease the risk of exercise-associated hypoglycemia. In the first phase of this study (in press), 22 subjects with type 1 diabetes went about their everyday lives while wearing an insulin pump, CGM, and accelerometer/heart rate monitor. After the monitoring period, the devices were downloaded and the data were used to augment an existing predictive low glucose suspend (PLGS) algorithm to incorporate activity. In a computer simulator, the PLGS algorithm reduced hypoglycemia by 64%, compared to 73% and 76% reductions for the accelerometer-augmented and HRM-augmented algorithms, respectively. In the next phase of this study, we seek to test the newly developed algorithm in a real-life setting in the form of a structured sports (soccer) camp to further see if modifications to the algorithm are required.

Official Title
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Accelerometer Use in the Prevention of Exercise-Associated Hypoglycemia in Type 1 Diabetes: Outpatient Exercise Protocol

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Computer algorithm to initiate pump suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of type 1 diabetes for 1-20 years. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed. Age 8 to 25 years old. On daily use of an insulin pump and not anticipating a change prior to the subject's completion of the study. Willingness to allow for CGM insertion (if not already using a study-designated CGM) for use during the study. HbA1c <10%. Parent/guardian and subject understand the study protocol and agree to comply with it. Informed Consent Form signed by the parent/guardian and Child Assent Form signed. Exclusion Criteria: A history of recent injury to body or limb, Addison's disease, muscular disorder, organ/bone marrow transplant, heart disease, or use of any medication or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the exercise protocol. Current use of glucocorticoid medication (by any route of administration). Current use of a beta blocker medication. Severe hypoglycemia resulting in seizure or loss of consciousness in the four weeks prior to sports camp (if a severe episode occurs after the first but prior to the scheduled second admission, the visit will be deferred). Active infection (if at the time of the planned second visit an infection is present, the visit will be deferred).

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: randomized crossover design. Subjects with type 1 diabetes participated in a structured soccer session on two separate dates at least one week apart. During one session a subject's basal insulin rate was continued (off-algorithm), while during the other session the algorithm (see algorithm monitoring below) was in effect (on-algorithm); the order of on- versus off-algorithm was chosen at random. The rate of hypoglycemia during exercise were compared between each group. Hypoglycemia was defined as (1) any meter blood glu cose (BG) reading of =60 mg/dl, (2) two consecutive meter BG readings =70 mg/dl done within one hour, or (3) any instance in which carbohydrates were given at a subject's request for symptoms of hypoglycemia (regardless of corre sponding meter BG reading).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: On-algorithm first, then Off-algorithm<br>Users will participate in two sports camp sessions while wearing an insulin pump, continuous glucose monitor, and accelerometer/heart rate monitor (to detect exercise), which can communicate electronically to a pump shutoff algorithm that insulin delivery should be shut off. On one sports day, the algorithm is turned on; on the other day, the algorithm is turned off. | Device: Computer algorithm to initiate pump suspension<br>* If the computer algorithm senses impending risk for hypoglycemia it sends an alert to an on-site physician to recommend a manual suspension of the subject's insulin pump<br>* Other names: Augmented predictive low glucose suspend algorithm;|
| Experimental: Off-algorithm first, then On-algorithm<br>Users will participate in two sports camp sessions while wearing an insulin pump, continuous glucose monitor, and accelerometer/heart rate monitor (to detect exercise), which can communicate electronically to a pump shutoff algorithm that insulin delivery should be shut off. On one sports day, the algorithm is turned on; on the other day, the algorithm is turned off. | Device: Computer algorithm to initiate pump suspension<br>* If the computer algorithm senses impending risk for hypoglycemia it sends an alert to an on-site physician to recommend a manual suspension of the subject's insulin pump<br>* Other names: Augmented predictive low glucose suspend algorithm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants Experiencing a Hypoglycemic Event During Scheduled Exercise | The primary outcome will be a hypoglycemic event defined as (1) any meter blood glucose (BG) reading of ≤60 mg/dl, (2) two consecutive meter BG readings ≤70 mg/dl done within one hour, or (3) any instance in which carbohydrates were given at a subject's request for symptoms of hypoglycemia | Measurements occurring during exercise (up to 8 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants With Hypoglycemia in the Post Exercise Period | A hypoglycemic event was defined as (1) any meter blood glucose (BG) reading of ≤60 mg/dl, (2) two consecutive meter BG readings ≤70 mg/dl done within one hour, or (3) any instance in which carbohydrates were given at a subject's request for symptoms of hypoglycemia | In the time following exercise until the following morning (up to 24 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 diabetes, Hypoglycemia, Accelerometer