Automated Insulin Delivery in Elderly With Type 1 Diabetes (AIDE T1D)

Study Overview
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Brief Summary
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A multi-center, randomized, crossover trial consisting of three sequential 12-week periods, with the HCL feature used during one period, the PLGS feature used during one period and SAP therapy (control) during one period. The crossover trial will be preceded by a run-in phase in which participants will receive training using the study devices (Dexcom G6 and Tandem t:slim X2 pump). After the last crossover period, participants will be given the opportunity to use study devices for an additional 12 weeks to assess preference of system use (PLGS, HCL or SAP) and associated characteristics, durability and safety in a more real-world setting with less frequent study contact.

Detailed Description
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Automated insulin delivery (AID) technologies hold the promise of optimizing glycemic control and reducing the burden of diabetes care for patients with Type 1 Diabetes (T1D). However, clinical trials of lower burden AID technologies have not included older adults in sufficient numbers to allow for focused evaluation of efficacy and quality of life (QOL) impacts that may differ from those observed in younger age groups. Most notably, primary endpoints have focused on reducing hyperglycemia, while avoidance of hypoglycemia is of upmost concern for older adults with T1D. T1D Exchange clinic registry data have shown severe hypoglycemia (SH) occurs more commonly in older adults with longstanding T1D than in younger individuals with events occurring just as often with HbA1c levels >8.0% as with HbA1c levels <7.0%. These data do not support the strategy of raising the HbA1c as being an effective approach for hypoglycemia prevention in older adults with T1D. In addition to acutely altered mental status, hypoglycemia is associated with an increased risk for falls leading to fractures, car accidents, emergency room (ER) visits, hospitalizations, and mortality resulting in substantial societal costs. The occurrence of hypoglycemia, hypoglycemia unawareness and fear of hypoglycemia have adverse effects on overall QOL of both individuals with T1D and their families. While continuous glucose monitoring (CGM) technology alone has the potential to be beneficial in reducing hypoglycemia in older patients, our preliminary data from the Wireless Innovations for Seniors with Diabetes Mellitus (WISDM) trial shows a majority of patients still have frequent hypoglycemia even when using CGM. Thus, knowledge of CGM alone may not be sufficient to avoid hypoglycemia in this population. Predictive low-glucose suspend algorithms have particular promise when the primary goal is hypoglycemia avoidance rather than glucose reduction. Whether the added complexity of closed loop systems provides additional glycemic benefit is not known. There is a critical need to determine whether automated insulin delivery can reduce hypoglycemia in the older adult population with T1D.

Official Title
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A Randomized Cross-over Trial Evaluating Automated Insulin Delivery Technologies on Hypoglycemia and Quality of Life in Elderly Adults With Type 1 Diabetes

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Device: Tandom t:slim X2 with HCL or PLGS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of type 1 diabetes Age ≥ 65 years old T1D Duration of at least 1 year HbA1c < 10.0% from point of care or local lab within the past 6 months Insulin regimen involves basal/bolus insulin via insulin pump or multiple daily injections Most recent GFR ≥ 30 ml/min/m^2 from local lab within the past 6 months Willingness to use a rapid acting insulin compatible with the Tandem t:slim X2 pump (currently aspart and lispro; other rapid acting insulins likely to be approved for pump use prior to study initiation such as Fiasp) Familiarity with and willingness to use a carbohydrate ratio for meal boluses Willing to use study devices and automated insulin delivery features Ability to download study devices at home or if not able to download at home willing to come into clinic to bring devices for download of data at visits and as needed for safety Participant is independently managing his/her diabetes with respect to insulin administration and glucose monitoring (may include assistance from spouse or other caregiver) Participant understands the study protocol, agrees to comply with it and is able to successfully pass the consent understanding assessment with no more than 2 attempts Participant comprehends written and spoken English At least 240 hours of CGM readings available during the end of run-in assessment At least 1.5% of time with CGM glucose levels < 70 mg/dL prior to SAP initiation Active prescription for glucagon and willing and able to have glucagon available Exclusion Criteria: Use of PLGS technology or HCL insulin delivery in the past 1 month History of 1 or more Diabetic Ketoacidosis episodes in the previous 6 months Clinical diagnosis by a primary care provider, neurologist or psychiatrist of dementia, in the investigator's opinion a suspected severe cognitive impairment such that it would preclude ability to understand the study or use devices, or a score of 6 or less out of 15 on the 5 min MoCA (5-min T MoCA Version 2.1) (mild cognitive impairment is not an exclusion) A condition, which in the opinion of the investigator or designee, would put the participant or study at risk, including severe vision or hearing impairment and any contraindication to the use of any of the study devices per FDA labeling Known adhesive allergy or skin reaction during the run-in pre-randomization phase or previous difficulty with pump and CGM insertions that would preclude participation in the randomized trial Concurrent use of any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas) Stage 4 or 5 renal disease The presence of a significant medical or psychiatric condition or use of a medication that in the judgment of the investigator may affect completion of any aspect of the protocol, or is likely to be associated with life expectancy of <1 year

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 trial with three 12-week crossover periods (HCL during one period, PLGS during one period, and SAP therapy (control) during one period) preceded by a run-in phase.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hybrid Closed Loop Control (HCL)<br>The HCL intervention arm will utilize the Tandom t:slim X2 with Control-IQ Technology and Dexcom G6 CGM | Device: Tandom t:slim X2 with HCL or PLGS<br>* The system components include the t:slim X2 with Control-IQ Technology and the Dexcom CGM G6. The modular control algorithm has a safety supervision module that limits insulin delivery to prevent hypoglycemia at all times. The algorithm gradually decreases hyperglycemia from bedtime to reach a target of 120 mg/dL by waking time. During awake hours, the control algorithm attempts to maintain glucose within a target range (112.5 to 160 mg/dL) with meal time insulin boluses delivered based on usual bolus procedures undertaken by patients on an insulin pump (Hybrid closed loop). The system components include the t:slim X2 with with Basal-IQ Technology and the Dexcom CGM G6. The PLGS System is able to stop and resume basal insulin delivery automatically in response to predicted or low sensor glucose values, thereby reducing the incidence and duration of hypoglycemic episodes. The pump includes the hypoglycemia minimization strategy that will issue insulin delivery commands.<br>* Other names: Tandom t:slim X2 with Basal-IQ Technology;|
| Active Comparator: Predictive Low-Glucose Insulin Suspension (PLGS)<br>The PLGS intervention arm will utilize the Tandom t:slim X2 with Basal-IQ Technology and Dexcom G6 CGM | Device: Tandom t:slim X2 with HCL or PLGS<br>* The system components include the t:slim X2 with Control-IQ Technology and the Dexcom CGM G6. The modular control algorithm has a safety supervision module that limits insulin delivery to prevent hypoglycemia at all times. The algorithm gradually decreases hyperglycemia from bedtime to reach a target of 120 mg/dL by waking time. During awake hours, the control algorithm attempts to maintain glucose within a target range (112.5 to 160 mg/dL) with meal time insulin boluses delivered based on usual bolus procedures undertaken by patients on an insulin pump (Hybrid closed loop). The system components include the t:slim X2 with with Basal-IQ Technology and the Dexcom CGM G6. The PLGS System is able to stop and resume basal insulin delivery automatically in response to predicted or low sensor glucose values, thereby reducing the incidence and duration of hypoglycemic episodes. The pump includes the hypoglycemia minimization strategy that will issue insulin delivery commands.<br>* Other names: Tandom t:slim X2 with Basal-IQ Technology;|
| No Intervention: Sensor-Augmented Pump (SAP)<br>The SAP arm will utilize the Tandem t:slim X2 without HCL or PLGS features turned on and Dexcom G6 CGM | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGM Measured Time <70 mg/dL | Percentage of sensor glucose values <70 mg/dL | 12 weeks for each arm of the crossover | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemia | Percentage of sensor glucose values <54 mg/dL | 12 weeks for each arm of the crossover | 
| Hypoglycemia | Frequency of CGM-measured hypoglycemic events | 12 weeks for each arm of the crossover | 
| Glucose Control | Mean glucose | 12 weeks for each arm of the crossover | 
| Glucose Control | Percentage of sensor glucose values 70 to 180 mg/dL | 12 weeks for each arm of the crossover | 
| Glucose Control | Coefficient of variation | 12 weeks for each arm of the crossover | 
| Hyperglycemia | Percentage of values >180 mg/dL | 12 weeks for each arm of the crossover | 
| Hyperglycemia | Percentage of values >250 mg/dL | 12 weeks for each arm of the crossover | 
| HbA1c | HbA1c | 12 weeks for each arm of the crossover | 
| Hypoglycemia Unawareness | Gold survey | 12 weeks for each arm of the crossover |