Feasibility of a Decision Support System to Reduce Glucose Variability in Subject With T1DM

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the safety and feasibility of a decision support system aimed at reducing glucose variability in T1DM patient using an insulin pump.

Detailed Description
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The overall aim of this proposed research is to demonstrate the safety and feasibility of a decision support system aimed at reducing glucose variability in T1DM patient using an insulin pump. The system will be deployed on our portable medical application platform (DiAs) and will include insulin pump treatment parameters optimization and an exercise risk warning system, capable of predicting hypoglycemia at the onset of physical activity and advising on mitigating alteration of treatment. A second phase of the trial will enroll additional users of insulin pumps, and subjects who treat their T1DM with the use of multiple daily injections (MDI) of insulin. MDI users should be administering the Lantus (glargine) dose at approximately the same time each day and use only one basal rate per day. MDI users will also use MySugr app to count carbohydrates for all meals that require insulin treatment.

Official Title
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Feasibility of a Decision Support System to Reduce Glucose Variability in Subject With T1DM

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Device: Decision Support System
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis based on investigator assessment, of type 1 diabetes for at least one year and either using insulin pump therapy for at least 6 months or MDI therapy (consisting of a of Lantus [glargine], Tresiba [degludec], or Levemir [Detemir] plus rapid-acting meal insulin) for at least 6 months; 1-2 basal insulin injections per day, consistent in timing and amount. A. Historical criteria for documented hyperglycemia (at least 1 must be met): i. Fasting glucose ≥126 mg/dL. ii. Two-hour oral glucose tolerance test (OGTT) glucose ≥200 mg/dL. iii. Hemoglobin A1c ≥6.5% documented. iv. Random glucose ≥200 mg/dL with symptoms. v. No data at diagnosis is available but the participant has a convincing history of hyperglycemia consistent with diabetes. B. Historical criteria for requiring insulin at diagnosis (1 must be met): i. Participant required insulin at diagnosis and continually thereafter. ii. 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 require insulin eventually and used continually. iii. Participant did not start insulin at diagnosis but continued to be hyperglycemic, had positive islet cell antibodies - consistent with latent autoimmune diabetes in adults (LADA) and did require insulin eventually and used continually. Age 21- 65years old. Females, not currently known to be pregnant. If female and sexually active, must agree to use a form of contraception to prevent pregnancy while participating in the study. A negative urine/blood pregnancy test will be required for all premenopausal women who are not surgically sterile. Subjects who become pregnant will be discontinued from the study. Demonstration of proper mental status and cognition for the study MDI subjects should be administering the Lantus (glargine), Tresiba [degludec], or Levemir [Detemir] dose at approximately the same time each day. CSII subjects must currently be using the bolus calculator function of the current insulin pump with pre-defined parameters for glucose goal, carbohydrate ratio, and insulin sensitivity factor. MDI users must currently be using Intensive Insulin Therapy including carbohydrate counting and use of pre-defined parameters for glucose goal, carbohydrate ratio, and insulin sensitivity factor. Willing to use Humalog (lispro) or Novolog (aspart) insulin during the study procedures for MDI subjects. CSII subjects must be willing to use the current bolus calculator pump parameters and enter all carbohydrate intake into the pump during the 28 day data collection period. MDI users must be willing to use their carbohydrate counting parameters for all meal dosing and enter the information into the MySugr app. Ability to access the Internet to provide data to the clinical team or to travel to the research center so that the study equipment and personal pump can be downloaded. An understanding of and willingness to follow the protocol and sign the informed consent. Exclusion Criteria: The presence of any of the following is an exclusion for the study: Diabetic ketoacidosis (DKA) in the 6 months prior to enrollment. Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment. Current treatment of a seizure disorder. Coronary artery disease or heart failure, unless written clearance is received from a cardiologist. Atrial or ventricular arrhythmias (benign premature atrial contractions [PACs] and premature ventricular contractions [PVCs] allowed) Cystic fibrosis. Pregnancy, breast-feeding, or intention of becoming pregnant over time of study procedures. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples: i. Inpatient psychiatric treatment in the past 6 months ii. Presence of a known adrenal disorder iii. Abnormal liver function test results (Transaminase >2 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function iv. Abnormal renal function test results (calculated GFR <60 mL/min/1.73m2); testing required for subjects with diabetes duration of greater than 5 years post onset of puberty v. Active gastroparesis vi. If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study vii. Uncontrolled thyroid disease (TSH undetectable or >10 mlU/L); testing required within three months prior to admission for subjects with a goiter, positive antibodies, or who are on thyroid hormone replacement, and within one year otherwise viii. Abuse of alcohol or recreational drugs ix. Infectious process not anticipated to be resolved prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis, deep tissue infection). x. Uncontrolled arterial hypertension (Resting diastolic blood pressure >100 mmHg and/or systolic blood pressure >180 mmHg). xi. Oral steroids xii. Uncontrolled microvascular complications such as current active proliferative diabetic retinopathy defined as proliferative retinopathy requiring treatment (e.g. laser therapy) in the past 12 months. A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the protocol. Basal Rates <0.01 units/hour for CSII subjects. More than one basal dose per day for MDI subjects Allergy for or intolerance of both Novolog (aspart) and Humalog (lispro) insulin for MDI subjects. Diagnosed food allergies. Current use of the following drugs and supplements: i. Regular acetaminophen user, or not willing to suspend acetaminophen 24 hours before and during the entire length of the trial ii. Any other medication that the investigator believes is a contraindication to the subject's participation Any reason for which the study MD considers the subject not properly fitted for the trial (i.e. insulin pump that does not record what is needed for the trial). Current enrollment in another clinical trial.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Decision Support System<br>Blinded continuous glucose monitor (CGM) data will be collected prior to the Experimental Admission and analyzed by the study team to determine the optimal insulin therapy parameters for each insulin pump and multiple daily injections (MDI) participant. These optimized parameters will be used during the Experimental Admission. | Device: Decision Support System<br>* The purpose of this study is to demonstrate the safety and feasibility of a Decision Support System aimed at reducing glucose variability in T1DM patient using an insulin pump or MDI. The system will be deployed on our portable medical application platform (DiAs) and will include the following elements: An insulin pump treatment parameters optimization routine, using a month of collected CGM/insulin/meal data An exercise risk warning system, capable of predicting hypoglycemia at the onset of physical activity and advising on mitigating alteration of treatment. A smart bolus calculator based on CGM glucose measurements and insulin sensitivity estimation.<br>|
| Active Comparator: Usual Care<br>Insulin pump and MDI participants will use their own insulin parameters, including basal rate, correction factor and carbohydrate-insulin ratio, and determine their own insulin usage during the Control Admission. | Other: Usual Care<br>* During the Control study admission, DiAs will be programmed with the home insulin dosing parameters. The study subject will use the home basal/bolus MDI or continuous subcutaneous insulin infusion (CSII) insulin regimen via the home insulin pens or pump and determine the amount of insulin to give for the entire admission per the subject's home carb counting parameters and as calculated by the DiAs meal screen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Variability (Coefficient of Variation) | Assess effectiveness of glucose variability (GV) advisory system in reducing glucose variability in T1DM patient using an insulin pump. | Duration of the 48 hour study admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Low Blood Glucose Index (LBGI) | Low blood glucose index (LBGI) by CGM with higher index indicating higher risk of hypoglycemia. Values <1 suggest minimal risk. Index of risk of low blood glucose excursion based on a standard formula for non-linear transformation of the blood glucose scale (Kovatchev BP, Cox DJ, Gonder-Frederick LA, Young-Hyman D, Schlundt D, Clarke WL: Assessment of risk for severe hypoglycemia among adults with IDDM (Insulin dependent diabetes mellitus): validation of the low blood glucose index. Diabetes Care 21:1870-1875, 1998) | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am). | 
| Percent Below 50 mg/dL | CGM measured blood sugar values below 50 mg/dL falls into the range of hypoglycemia which have the potential to lead to unconsciousness or death. Thus, less time below 50 mg/dL is considered a better outcome. | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 
| Percent Below 60 mg/dL | CGM measured blood sugar values below 60 mg/dL falls into the range of hypoglycemia which have the potential to lead to unconsciousness or death. Thus, less time below 60 mg/dL is considered a better outcome. | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 
| Percent Below 70 mg/dL | CGM measured blood sugar values below 70 mg/dL falls into the range of hypoglycemia which have the potential to lead to unconsciousness or death. Thus, less time below 70 mg/dL is considered a better outcome. | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 
| Percent Between 70 and 180 mg/dL | CGM measured blood sugar values between 70 abd 180 mg/dL are considered to be desirable. A higher percentage of time in this range is indicative of a desirable outcome. | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 
| Percent Above 180 mg/dL | CGM measured blood sugar values above 180 mg/dL are considered to be undesirable. Thus, less time spent above 180 mg/dL is considered a positive outcome | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 
| Percent Above 250 mg/dL | CGM measured blood sugar values above 250 mg/dL are considered to be undesirable. Thus, less time spent above 250 mg/dL is considered a positive outcome | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 
| Percent Above 300 mg/dL | CGM measured blood sugar values above 300 mg/dL are considered to be undesirable. Thus, less time spent above 300 mg/dL is considered a positive outcome | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 
| Average Glycemia (mg/dL) | Average glycemia is a measure of the average CGM value in mg/dL during the 48 hour study admission. A lower value, without approaching hypoglycemia, is indicative of a desirable outcome. | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 
| Total Insulin Used | This measure is an average of the total amount of insulin (both basal and bolus) used by participants during the study admission. | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 
| Basal Insulin Used | This measure is an average of the total amount of basal insulin used by participants during the study admission. | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 
| Total Rescue Carbohydrates (CHO) (Grams) | The average of the total amount of rescue carbohydrates (grams) administered during the study admission under safety protocols. Administering fewer carbohydrates is a desirable outcome because it indicates better control. | 48 hour study admission, outcomes were further divided into segments of the day: overnight (11 pm- 7 am), and around meals (the 4 h following lunch and dinner, breakfast excluded due to exercise). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes Mellitus (T1DM), Artificial Pancreas Project (APP), Diabetes Assistant (DiAs), Insulin Pump, Continuous Glucose Monitor, Exercise, Glucose Variability, Decision Support System, Multiple Daily Injections (MDI)