Diabetes Mellitus, Type 1, Type 1 Diabetes
Conditions
Brief summary
This study has been designed as a prospectively enrolled, randomized sequence, 2-way crossover study of device performance, tolerability and safety of an investigational insulin infusion set using a coil-reinforced soft polymer indwelling cannula versus a commercial insulin infusion set using a soft Teflon indwelling cannula, during two 7-day home use periods with 4 in-clinic euglycemic clamp sessions during each of the 7-day periods. After a wash-out period, subjects will cross over into the investigational or control group, respectively.
Interventions
DEVICEsoft Teflon indwelling catheter
Insulin infusion set will be used for up to 7 days of continuous use or until failure
Insulin infusion set will be used for up to 7 days of continuous use or until failure
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
AMCR Institute
Integrated Medical Development
Capillary Biomedical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DEVICE_FEASIBILITY
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Participants are 18 - 70 years of age inclusive 2. Participant is in generally good health, as determined by the investigator 3. Participant is willing and able to individually complete written informed consent and agrees to comply with all study related testing and examinations 4. Participant must be geographically stable (e.g., expects to be available and capable of returning for all study specified test and examinations) during the study period 5. Participant has been diagnosed with T1DM for at least 12 months 6. C-peptide \<0.6 nmol/L at screening 7. Participant has been using insulin pump therapy for at least 6 months and is currently using a Medtronic MiniMed pump, model series 530 or higher. Use of 670G in auto mode is acceptable. 8. Participant can provide a minimum of 14 days of insulin pump data to demonstrate pump use compliance 9. Participant is willing to perform frequent (4 times per day or more) self-monitoring of blood glucose (SMBG), including before meals and before bed, and using a meter and test strips provided by the sponsor during the two weeks of active treatment. This includes participants who are currently using real-time continuous glucose monitoring and may continue to do so, but must also collect SMBG values as instructed. 10. Participant is willing to perform serum ketone measurements whenever the blood glucose is determined to be greater than 250 mg/dL after extended fasting (e.g. overnight or more than five hours after a meal) using a ketone meter and strips provided by the sponsor 11. Participant has BMI in the range 20 - 35 kg/m2 inclusive 12. Participant has experience infusing a rapid-acting insulin analog for at least 6 months 13. Participant has been using or is willing to use a Continuous Glucose Monitor (CGM) (reading data available for at least 80% of time for a week of data collection during the screening period). Participants already using - Dexcom G6 real time CGM may continue to use their own CGM unit; participants not using the G6 will be provided with a G6 monitor. All participants will be provided with CGM disposables for use during the treatment period. 14. Participant has ability to understand and comply with protocol procedures and to provide informed consent 15. HbA1c ≤8.5% 16. Stable body weight in the 3 months prior to enrollment (change in body weight \<5%)
Exclusion criteria
An individual who meets any of the following criteria will be excluded from participation in this study: 1. Participants whose average total daily insulin dose exceeds 85 units/day (i.e., typically change insulin reservoirs more often than every 4 days on average) 2. Participants who routinely change their commercial insulin infusion sets on average less often than every 4.5 days 3. Female participant is pregnant or nursing 4. Participant has abnormal skin at intended device infusion sites (existing infection, inflammation, burns, or other extensive scarring) 5. Participant has hemoglobin \<12.0 g/dL or potassium \< 3.5 milliequivalent/L at screening 6. Participant has documented history in last 6 months of severe hypoglycemia associated with cognitive dysfunction sufficiently severe to require third party intervention or a history of impaired awareness of hypoglycemia. 7. Participant has a history of diabetic ketoacidosis in the last 6 months 8. Participant has known cardiovascular disease considered to be clinically relevant by the investigator 9. Participant has known arrhythmias considered to be clinically relevant by the investigator 10. Participant has known history of: 1. Cushing's Disease, 2. Pancreatic islet cell tumor, or 3. Insulinoma 11. Participant has: 1. Lipodystrophy, 2. Extensive lipohypertrophy, as assessed by the investigator 12. Participant is undergoing current treatment with: 1. Systemic oral or intravenous corticosteroids, 2. Monoamine oxidase (MAO) inhibitors, 3. Non-selective systemic beta-blockers, 4. Growth hormone, 5. Thyroid hormones, unless use has been stable during the past 3 months 6. SGLT2 inhibitors 13. Participant has significant history of any of the following, that in the opinion of the investigator would compromise the participant's safety or successful study participation: 1. Alcoholism, 2. Drug abuse 14. Significant acute or chronic illness, that in the investigator's opinion, might interfere with participant safety or integrity of study results 15. Planned operation, MRI or CT which require removal of infusion set or CGM sensor during wear periods 16. Current treatment with systemic (oral or IV) corticosteroids, monoamine oxidase (MAO) inhibitors, non-selective beta-blockers, growth hormone, herbal products that, in the opinion of the investigator, may alter insulin sensitivity or confer undue risk to the participant's participation in the study or non-routine vitamins. Furthermore, thyroid hormones are not allowed unless the use of these has been stable during the past 3 months. 17. Current participation in another clinical drug or device study 18. Inability of the participant to comply with all study procedures or to understand the participant instructions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Endpoint is the Rate of Decline (s) Over Wear Time (DOI, Day 3, Day 5, Day 7) of the Natural Logarithm of the Area Under the Glucose Infusion Rate Curve [ln (AUC0-300(GIR))]. | 7 days | The primary endpoint will be compared between the treatment groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Maximum Insulin Concentration (Cmax) | 7 days | Cmax is the maximum insulin concentration between t=0 (bolus) and t=300 minutes. |
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Early) Maximum Insulin Concentration [t50%(Early)] | 7 days | The time to half-maximal insulin concentration- early (before peak) |
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Mean-residence Time (MRT) of Insulin | 7 days | Mean residence time quantifies the sum of average absorption time and average systemic residence time. |
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-Maximum Insulin Concentration (Tmax) | 7 days | The Time-to-Maximum Glucose Infusion (GIR) rate, tmax (GIR) is the minute between the time corresponding to the GIR max and Time 0. |
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Insulin Early Exposure: AUC0-60 | 7 days | Area under the insulin concentration curve in the first 60 minutes after bolus administration |
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Late) Maximum Insulin Concentration [t50%(Late)] | 7 days | Time at which 50% of the maximum insulin concentration was reached. |
| Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Area Under the Curve (AUC0-300) | 7 days | The area under the insulin concentration curve until 300 minutes after bolus administration |
Countries
United States
Participant flow
Recruitment details
Study participants were recruited from the existing Type 1 diabetes database at the study center and from referrals from other diabetes treatment clinics in surrounding areas.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants were randomized to either the soft Teflon indwelling cannula group or the coil-reinforced soft polymer indwelling cannula group in treatment period 1. Then after a 2-week washout/rest (±1 week), participants crossed over into treatment period 2 using either the soft Teflon indwelling cannula or the coil-reinforced soft polymer indwelling cannula. The participant wore each infusion set up to 7 consecutive days in each treatment period. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 (1 Week) | Withdrawal by Subject | 0 | 1 |
| Treatment Period 2 (1 Week) | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 9.24 |
| BMI | 27.6 kg/m2 STANDARD_DEVIATION 3.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 3 / 6 | 2 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 |
Outcome results
Primary
The Primary Endpoint is the Rate of Decline (s) Over Wear Time (DOI, Day 3, Day 5, Day 7) of the Natural Logarithm of the Area Under the Glucose Infusion Rate Curve [ln (AUC0-300(GIR))].
The primary endpoint will be compared between the treatment groups.
Time frame: 7 days
Population: Intent to Treat (ITT) population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Coil-reinforced Soft Polymer Indwelling Cannula | The Primary Endpoint is the Rate of Decline (s) Over Wear Time (DOI, Day 3, Day 5, Day 7) of the Natural Logarithm of the Area Under the Glucose Infusion Rate Curve [ln (AUC0-300(GIR))]. | -0.102 Slope |
| Soft Teflon Indwelling Cannula | The Primary Endpoint is the Rate of Decline (s) Over Wear Time (DOI, Day 3, Day 5, Day 7) of the Natural Logarithm of the Area Under the Glucose Infusion Rate Curve [ln (AUC0-300(GIR))]. | -0.097 Slope |
Secondary
Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Area Under the Curve (AUC0-300)
The area under the insulin concentration curve until 300 minutes after bolus administration
Time frame: 7 days
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Area Under the Curve (AUC0-300) | Day 0 | 9084 mU*min/L | Standard Deviation 2826 |
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Area Under the Curve (AUC0-300) | Day 7 | 6920 mU*min/L | Standard Deviation 1908 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Area Under the Curve (AUC0-300) | Day 0 | 8982 mU*min/L | Standard Deviation 1453 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Area Under the Curve (AUC0-300) | Day 7 | 7313 mU*min/L | Standard Deviation 2483 |
Secondary
Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Insulin Early Exposure: AUC0-60
Area under the insulin concentration curve in the first 60 minutes after bolus administration
Time frame: 7 days
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Insulin Early Exposure: AUC0-60 | Day 0 | 2131 mU*min/L | Standard Deviation 923.1 |
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Insulin Early Exposure: AUC0-60 | Day 7 | 3626 mU*min/L | Standard Deviation 922.9 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Insulin Early Exposure: AUC0-60 | Day 0 | 2200 mU*min/L | Standard Deviation 940.6 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Insulin Early Exposure: AUC0-60 | Day 7 | 3840 mU*min/L | Standard Deviation 2055 |
Secondary
Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Maximum Insulin Concentration (Cmax)
Cmax is the maximum insulin concentration between t=0 (bolus) and t=300 minutes.
Time frame: 7 days
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Maximum Insulin Concentration (Cmax) | Day 0 | 57.8 mU/L | Standard Deviation 21.51 |
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Maximum Insulin Concentration (Cmax) | Day 7 | 86.6 mU/L | Standard Deviation 23.95 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Maximum Insulin Concentration (Cmax) | Day 0 | 62.3 mU/L | Standard Deviation 20.94 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Maximum Insulin Concentration (Cmax) | Day 7 | 96.9 mU/L | Standard Deviation 49.12 |
Secondary
Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Mean-residence Time (MRT) of Insulin
Mean residence time quantifies the sum of average absorption time and average systemic residence time.
Time frame: 7 days
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Mean-residence Time (MRT) of Insulin | Day 0 | 121.8 min | Standard Deviation 25.1 |
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Mean-residence Time (MRT) of Insulin | Day 7 | 77.4 min | Standard Deviation 8.92 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Mean-residence Time (MRT) of Insulin | Day 0 | 117.7 min | Standard Deviation 27.08 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Mean-residence Time (MRT) of Insulin | Day 7 | 75.9 min | Standard Deviation 14.07 |
Secondary
Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Early) Maximum Insulin Concentration [t50%(Early)]
The time to half-maximal insulin concentration- early (before peak)
Time frame: 7 days
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Early) Maximum Insulin Concentration [t50%(Early)] | Day 0 | 22.8 min | Standard Deviation 11.34 |
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Early) Maximum Insulin Concentration [t50%(Early)] | Day 7 | 11.5 min | Standard Deviation 4.13 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Early) Maximum Insulin Concentration [t50%(Early)] | Day 0 | 29.1 min | Standard Deviation 10.59 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Early) Maximum Insulin Concentration [t50%(Early)] | Day 7 | 14.8 min | Standard Deviation 5.21 |
Secondary
Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Late) Maximum Insulin Concentration [t50%(Late)]
Time at which 50% of the maximum insulin concentration was reached.
Time frame: 7 days
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Late) Maximum Insulin Concentration [t50%(Late)] | Day 0 | 156.8 min | Standard Deviation 34.13 |
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Late) Maximum Insulin Concentration [t50%(Late)] | Day 7 | 67.8 min | Standard Deviation 13.2 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Late) Maximum Insulin Concentration [t50%(Late)] | Day 0 | 156.5 min | Standard Deviation 44.47 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-50% (Late) Maximum Insulin Concentration [t50%(Late)] | Day 7 | 76.3 min | Standard Deviation 28.87 |
Secondary
Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-Maximum Insulin Concentration (Tmax)
The Time-to-Maximum Glucose Infusion (GIR) rate, tmax (GIR) is the minute between the time corresponding to the GIR max and Time 0.
Time frame: 7 days
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-Maximum Insulin Concentration (Tmax) | Day 0 | 65.8 min | Standard Deviation 30.07 |
| Coil-reinforced Soft Polymer Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-Maximum Insulin Concentration (Tmax) | Day 7 | 25.0 min | Standard Deviation 7.07 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-Maximum Insulin Concentration (Tmax) | Day 0 | 67.5 min | Standard Deviation 25.05 |
| Soft Teflon Indwelling Cannula | Mean Differences (Within Treatments Over Time Between Day 0 and Day 7) in Time-to-Maximum Insulin Concentration (Tmax) | Day 7 | 31.0 min | Standard Deviation 16.73 |