Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes Mellitus, Diabetes, Sensor Augmented Pump, Hypoglycemia
Brief summary
A 6-week crossover study will compare PLGS to SAP outcomes in adults and youth \> 6 years old with type 1 diabetes (T1D).
Detailed description
1. Screening and Enrollment * Informed consent will be signed and eligibility will be assessed * History and physical examination * HbA1c measurement * Urine or serum pregnancy test (if applicable) * Evaluation of Continuous Glucose Monitoring (CGM) and pump experience 2. CGM and (Sensor Augmented Pump) SAP Training Period at Home All eligible participants will be assessed based on their CGM and pump experience to determine if the CGM Training Period, the SAP Training Period, or both are required. 1. CGM Training Period (10-14 days): Participants currently using a CGM may skip the CGM Training Period per investigator discretion, generally requiring that CGM has been used on at least 85% of days during the prior 4 weeks. 2. SAP Training Period (14-28 days): Participants currently using a Tandem pump concomitantly with a Dexcom CGM may skip both the CGM Training and the SAP Training periods per investigator discretion. i. The Tandem SAP pump will be used during the SAP Training Period and pump training will be customized based on prior pump experience 3. PLGS Pilot Phase Prior to the initiation of the crossover trial, 10 adult participants will use the Tandem PLGS pump and CGM system in a 10-day Pilot Period. Data will be evaluated for system usability and predetermined safety metrics before participants ≥12 years old can be randomized into the crossover trial. 4. Randomized Crossover Trial The crossover trial will begin after the data from the Pilot Period have been reviewed. Enrollment of participants 6 to 11 years old will be deferred until data from 100 post-randomization PLGS participant-days have been evaluated from participants 12 to 17 years old and the same predetermined safety metrics used to evaluate the Pilot Period have been satisfied. At the Crossover Trial initiation visit, the following will be done: * The clinician will confirm the participant's willingness to participate in the crossover trial * The participant's HbA1c level will be measured * Random assignment to Group A or Group B Group A: intervention period first (PLGS), control period second (SAP) Group B: control period first (SAP), intervention period second (PLGS) During each of the two 3-week periods, a phone, email, or text contact will occur at 2 and 14 days, and a clinic visit at 7 and 21 days. HbA1c will be measured at the end of each period.
Interventions
DEVICEPredictive Low Glucose Suspend
Application of Predictive Low Glucose Suspend
Sponsors
Jaeb Center for Health Research
Tandem Diabetes Care, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multi-center, randomized, crossover design, consisting of two 3-week periods, with the PLGS System used during one period and SAP therapy used during the other period. The crossover trial will be preceded by a run-in phase in which participants may receive training using the study devices. For 10 adult participants, a PLGS Pilot Period will proceed to the crossover trial to ensure safety and usability objectives are met prior to the start of the crossover trial.
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Clinical diagnosis, based on investigator assessment, of T1D treated with insulin via an insulin pump or injections for at least 1 year, with no major change in the intensity of insulin therapy in the past 3 months (e.g. switching from injections to pump) * 2\. Age ≥6.0 years old * 3\. For participants \<18 years old, living with one or more parents or guardians committed to participating in training and able to contact the participant in case of an emergency * 4\. For females, not currently known to be pregnant * \- If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative serum or urine pregnancy test will be required for all females of child-bearing potential. Subjects who become pregnant will be discontinued from the study. Also, subjects who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued. * 5\. Investigator has confidence that the participant can successfully use all study devices and is capable of adhering to the protocol
Exclusion criteria
* 1\. Anticipated need to use acetaminophen during study participation * 2\. Participation in another pharmaceutical or device trial at the time of enrollment or plan to participate in another study during the time period of participation in this study * 3\. Employed by, or having immediate family members employed by Tandem; or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial * 4\. A condition, which in the opinion of the investigator or designee, would put the participant or study at risk including any contraindication to the use of any of the study devices per FDA labelling * \- Individuals should not be enrolled with uncontrolled thyroid disease, renal failure (e.g., dialysis or estimated glomerular filtration (eGFR) \<30), hemophilia or another major bleeding disorder, or unstable cardiovascular disease. * \- Laboratory testing and other work up needed to determine that an individual is a suitable candidate for the study should be performed as part of usual care.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycemia < 70 mg/dL | 3 weeks | Percentage of time CGM \<70 mg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycemia <50 mg/dL | 3 weeks | Percentage of time CGM \<50 mg/dL |
| Hypoglycemia AOC <70 mg/dL | 3 weeks | Area Over Curve (AOC) \<70 mg/dL |
| Low Blood Glucose Index (LBGI) | 3 weeks | Low blood glucose index (LBGI) by CGM with higher index indicating higher risk of hypoglycemia. LBGI ≤ 1.1 is associated with minimal risk of hypoglycemia, 1.1 \< LBGI ≤ 2.5 is associated with a low risk of hypoglycemia, 2.5 \< LBGI ≤ 5.0 is associated with a moderate risk of hypoglycemia, and LBGI \> 5.0 is associated with high risk of hypoglycemia. |
| Hypoglycemic Events Per Week | 3 weeks | A hypoglycemia event was defined as at least two sensor values \<54 mg/dL that were ≥15 min apart with no intervening values \>54 mg/dL. At least two sensor values \>70 mg/dL that are ≥30 min apart with no intervening values \<70 mg/dL are required to end a hypoglycemic event. |
| Hypoglycemia <60 mg/dL | 3 weeks | Percentage of time CGM \<60 mg/dL |
| Hyperglycemia >250 mg/dL | 3 weeks | Percentage of time CGM \>250 mg/dL |
| Hyperglycemia >180 mg/dL | 3 weeks | Percentage of time CGM \>180 mg/dL |
| Area Under Curve >180 mg/dL | 3 weeks | Hyperglycemia Area Under Curve of CGM \>180 mg/dL |
| High Blood Glucose Index (HBGI) | 3 weeks | High Blood Glucose Index (HBGI) is a measure of Hyperglycemic Risk based on frequency and severity of hyperglycemic events. HBGI \< 4.5 is associated with lower risk of hyperglycemia, 4.5 \< HBGI \< 9 is associated with a moderate risk of hyperglycemia and HBGI \> 9 is associated with high risk of hyperglycemia |
| Time in Range 70-180 mg/dL | 3 weeks | Percentage of time CGM in range 70 to 180 mg/dL |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PLGS First, Then SAP Participants were randomized to use the Predictive Low-Glucose Suspend (PLGS) system first for 3 weeks, then the switch to the sensor-augmented pump (SAP) arm for 3 weeks. | 52 |
| SAP First, Then PLGS Participants were randomized to use the sensor-augmented pump (SAP) system first for 3 weeks, then the switch to the Predictive Low-Glucose Suspend (PLGS) arm for 3 weeks. | 51 |
| Total | 103 |
Baseline characteristics
| Characteristic | PLGS First, Then SAP | SAP First, Then PLGS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 29 Participants | 31 Participants | 60 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 19 Participants | 41 Participants |
| Age, Continuous | 25 years STANDARD_DEVIATION 18 | 23 years STANDARD_DEVIATION 16 | 24 years STANDARD_DEVIATION 17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 47 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) White | 44 Participants | 38 Participants | 82 Participants |
| Region of Enrollment United States | 52 Participants | 51 Participants | 103 Participants |
| Sex: Female, Male Female | 26 Participants | 32 Participants | 58 Participants |
| Sex: Female, Male Male | 26 Participants | 19 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 103 | 0 / 103 |
| other Total, other adverse events | 58 / 103 | 59 / 103 |
| serious Total, serious adverse events | 0 / 103 | 2 / 103 |
Outcome results
Primary
Hypoglycemia < 70 mg/dL
Percentage of time CGM \<70 mg/dL
Time frame: 3 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baseline | Hypoglycemia < 70 mg/dL | 3.6 percentage of time |
| Intervention Arm | Hypoglycemia < 70 mg/dL | 2.6 percentage of time |
| Control Arm | Hypoglycemia < 70 mg/dL | 3.2 percentage of time |
Secondary
Area Under Curve >180 mg/dL
Hyperglycemia Area Under Curve of CGM \>180 mg/dL
Time frame: 3 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baseline | Area Under Curve >180 mg/dL | 14.7 mg*hr/dL |
| Intervention Arm | Area Under Curve >180 mg/dL | 15.8 mg*hr/dL |
| Control Arm | Area Under Curve >180 mg/dL | 16.9 mg*hr/dL |
Secondary
High Blood Glucose Index (HBGI)
High Blood Glucose Index (HBGI) is a measure of Hyperglycemic Risk based on frequency and severity of hyperglycemic events. HBGI \< 4.5 is associated with lower risk of hyperglycemia, 4.5 \< HBGI \< 9 is associated with a moderate risk of hyperglycemia and HBGI \> 9 is associated with high risk of hyperglycemia
Time frame: 3 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baseline | High Blood Glucose Index (HBGI) | 6.7 index score |
| Intervention Arm | High Blood Glucose Index (HBGI) | 6.9 index score |
| Control Arm | High Blood Glucose Index (HBGI) | 7.4 index score |
Secondary
Hyperglycemia >180 mg/dL
Percentage of time CGM \>180 mg/dL
Time frame: 3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Hyperglycemia >180 mg/dL | 32 percentage of time | Standard Deviation 17 |
| Intervention Arm | Hyperglycemia >180 mg/dL | 32 percentage of time | Standard Deviation 15 |
| Control Arm | Hyperglycemia >180 mg/dL | 33 percentage of time | Standard Deviation 16 |
Secondary
Hyperglycemia >250 mg/dL
Percentage of time CGM \>250 mg/dL
Time frame: 3 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baseline | Hyperglycemia >250 mg/dL | 7 percentage of time |
| Intervention Arm | Hyperglycemia >250 mg/dL | 8 percentage of time |
| Control Arm | Hyperglycemia >250 mg/dL | 8 percentage of time |
Secondary
Hypoglycemia <50 mg/dL
Percentage of time CGM \<50 mg/dL
Time frame: 3 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baseline | Hypoglycemia <50 mg/dL | 0.3 percentage of time |
| Intervention Arm | Hypoglycemia <50 mg/dL | 0.2 percentage of time |
| Control Arm | Hypoglycemia <50 mg/dL | 0.3 percentage of time |
Secondary
Hypoglycemia <60 mg/dL
Percentage of time CGM \<60 mg/dL
Time frame: 3 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baseline | Hypoglycemia <60 mg/dL | 1.2 percentage of time |
| Intervention Arm | Hypoglycemia <60 mg/dL | 0.9 percentage of time |
| Control Arm | Hypoglycemia <60 mg/dL | 1.2 percentage of time |
Secondary
Hypoglycemia AOC <70 mg/dL
Area Over Curve (AOC) \<70 mg/dL
Time frame: 3 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baseline | Hypoglycemia AOC <70 mg/dL | 0.31 mg*hr/dL |
| Intervention Arm | Hypoglycemia AOC <70 mg/dL | 0.25 mg*hr/dL |
| Control Arm | Hypoglycemia AOC <70 mg/dL | 0.30 mg*hr/dL |
Secondary
Hypoglycemic Events Per Week
A hypoglycemia event was defined as at least two sensor values \<54 mg/dL that were ≥15 min apart with no intervening values \>54 mg/dL. At least two sensor values \>70 mg/dL that are ≥30 min apart with no intervening values \<70 mg/dL are required to end a hypoglycemic event.
Time frame: 3 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baseline | Hypoglycemic Events Per Week | 1.1 events/week |
| Intervention Arm | Hypoglycemic Events Per Week | 0.8 events/week |
| Control Arm | Hypoglycemic Events Per Week | 1.1 events/week |
Secondary
Low Blood Glucose Index (LBGI)
Low blood glucose index (LBGI) by CGM with higher index indicating higher risk of hypoglycemia. LBGI ≤ 1.1 is associated with minimal risk of hypoglycemia, 1.1 \< LBGI ≤ 2.5 is associated with a low risk of hypoglycemia, 2.5 \< LBGI ≤ 5.0 is associated with a moderate risk of hypoglycemia, and LBGI \> 5.0 is associated with high risk of hypoglycemia.
Time frame: 3 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baseline | Low Blood Glucose Index (LBGI) | 0.9 index score |
| Intervention Arm | Low Blood Glucose Index (LBGI) | 0.8 index score |
| Control Arm | Low Blood Glucose Index (LBGI) | 0.9 index score |
Secondary
Time in Range 70-180 mg/dL
Percentage of time CGM in range 70 to 180 mg/dL
Time frame: 3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Time in Range 70-180 mg/dL | 64 percentage of time | Standard Deviation 15 |
| Intervention Arm | Time in Range 70-180 mg/dL | 65 percentage of time | Standard Deviation 15 |
| Control Arm | Time in Range 70-180 mg/dL | 63 percentage of time | Standard Deviation 15 |