Type 1 Diabetes Mellitus
Conditions
Keywords
hyaluronidase, infusion sets, insulin pump, Continuous glucose monitor
Brief summary
This research study examines the effect of hyaluronidase on the length of time of insulin infusion set wear. The aim of the study is to improve the length of time that an infusion set can be worn by infusing hyaluronidase directly into the insulin infusion site.
Detailed description
The investigators would like to see if the use of hyaluronidase will improve insulin infusion set survival and improve the onset of insulin action. The investigators will also assess the accuracy of the Dexcom G4P sensors with extended site use beyond the 7 day FDA approved time frame. The use of sensor information combined with the knowledge of infused insulin from pump therapy could potentially help us detect when an infusion set is beginning to fail. Information from the sensor function to the point of failure, and sensor function in response to Tylenol may allow us to develop special formulas to determine when a sensor is not working well. This will be very important for creating an artificial pancreas. Thirty subjects will be enrolled. Fifteen patients from each of the two sites: Stanford University and University of Colorado.
Interventions
DRUGHyaluronidase
150 units/ml - subjects injected 1 milliliter (ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.
OTHERControl
No hyaluronidase administered into insulin infusion set.
Sponsors
University of Colorado, Denver
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of type 1 diabetes for at least one year and using an insulin pump for at least 3 months 2. Total daily insulin dose of at least 0.4 units/kg/day 3. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed. 4. Age 12 to 45 years 5. Hemoglobin A1c level less than or equal to 10% 6. Willingness to infuse 1 ml of hyaluronidase (Hylenex) into the insulin infusion set after insertion on day 1 and day 3 of the week they are assigned to use hyaluronidase 7. Willingness to use a Silhouette or Comfort insulin infusion set throughout the study. The set includes the Duo Infusion Tubing for infusion of hyaluronidase (Hylenex). 8. Willingness to eat the same breakfast each morning for the first two weeks of the study 9. Willing to take two 500mg tablets of Tylenol Regular Strength and monitor glucose levels at ½, 1, 2, 4, 6, and 8 hours later. 10. For females, not currently known to be pregnant 11. An understanding of and willingness to follow the protocol and sign the informed consent 12. Must be able to understand spoken or written English
Exclusion criteria
1. Diabetic ketoacidosis in the past 6 months 2. Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment 3. Known tape allergies 4. Current treatment for a seizure disorder 5. Cystic fibrosis 6. Active infection 7. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples: 8. Inpatient psychiatric treatment in the past 6 months for either the subject or the subject's primary care giver (i.e., parent or guardian) 9. Presence of a known adrenal disorder 10. 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 11. Abuse of alcohol 12. Use of an OmniPod insulin infusion pump 13. Pregnant or lactating females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Insulin Infusion Set Wear as a Measure of the Effect of Hyaluronidase Treatment | Up to 4 weeks | Average (mean) days of wear are presented for each group. A longer period of wear was considered a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Glycemic Excursion | Up to 24 hours post infusion | The effects of hyaluronidase on post-prandial glucodymamic parameters is presented as the estimated glycemic excursion, a composite value which was calculated based on peak glucose concentration (Cmax), time to Cmax (Tmax), time to early half-maximal glucose concentration (t50%), time to late t50%, and area under the curve (AUC) of glucose concentrations at time intervals of 120 and 240 minutes, with or without hyaluronidase. Estimated glycemic excursion for a patient with Type 1 diabetes that is less than 80 mg/dL is considered acceptable. |
| Pain Tolerability of Hyaluronidase Injections | Up to 4 weeks | Patients recorded pain experience at the infusion site (at time of injection and pain each day of wear) in subject diaries on a 0-5 pain scale (0 = no pain and 5 = worst pain imaginable). The number of diary entries are presented by scale category. |
Countries
United States
Participant flow
Recruitment details
A total of 30 subjects with Type 1 diabetes between 12-45 years were enrolled at 2 academic medical centers. 28 subjects completed the full 4 weeks of the study. 2 subjects discontinued for the study early. The last subject completed in March 2015.
Participants by arm
| Arm | Count |
|---|---|
| Hylenex, Then Control Participants were first assigned to the control arm. They received active treatment (Hylenex) on weeks 2 and 4.
On weeks 1 and 3 (control weeks) no Hylenex was administered.
On weeks 2 and 4 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear. | 15 |
| Control, Then Hylenex Participants were first assigned to the control arm. They received active treatment (Hylenex) on weeks 2 and 4.
On weeks 1 and 3 (control weeks) no Hylenex was administered.
On weeks 2 and 4 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Week 1 | Adverse Event | 1 | 0 |
| Week 3 | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Control, Then Hylenex | Hylenex, Then Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 13 Participants | 27 Participants |
| Age, Continuous | 30.06919 years STANDARD_DEVIATION 8.33594 | 24.80552 years STANDARD_DEVIATION 8.22924 | 27.52718 years STANDARD_DEVIATION 8.57883 |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 18 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 30 | 17 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Duration of Insulin Infusion Set Wear as a Measure of the Effect of Hyaluronidase Treatment
Average (mean) days of wear are presented for each group. A longer period of wear was considered a better outcome.
Time frame: Up to 4 weeks
Population: Thirty subjects were enrolled in this study; 28 completed all scheduled visits. Therefore, 117 total weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 standard weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hyaluronidase | Duration of Insulin Infusion Set Wear as a Measure of the Effect of Hyaluronidase Treatment | 5.7 Days of wear | Standard Deviation 1.7 |
| Control | Duration of Insulin Infusion Set Wear as a Measure of the Effect of Hyaluronidase Treatment | 5.4 Days of wear | Standard Deviation 1.9 |
Secondary
Maximum Glycemic Excursion
The effects of hyaluronidase on post-prandial glucodymamic parameters is presented as the estimated glycemic excursion, a composite value which was calculated based on peak glucose concentration (Cmax), time to Cmax (Tmax), time to early half-maximal glucose concentration (t50%), time to late t50%, and area under the curve (AUC) of glucose concentrations at time intervals of 120 and 240 minutes, with or without hyaluronidase. Estimated glycemic excursion for a patient with Type 1 diabetes that is less than 80 mg/dL is considered acceptable.
Time frame: Up to 24 hours post infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hyaluronidase | Maximum Glycemic Excursion | Day 1 0-1 hour of infusion set | 43.5 mg/dL | Standard Deviation 44.5 |
| Hyaluronidase | Maximum Glycemic Excursion | Day 1 12-24 hours of infusion set | 36.9 mg/dL | Standard Deviation 35.1 |
| Hyaluronidase | Maximum Glycemic Excursion | Day 2 24-48 hours of infusion set | 56.4 mg/dL | Standard Deviation 25.9 |
| Control | Maximum Glycemic Excursion | Day 1 0-1 hour of infusion set | 69.5 mg/dL | Standard Deviation 47.4 |
| Control | Maximum Glycemic Excursion | Day 1 12-24 hours of infusion set | 72 mg/dL | Standard Deviation 48.8 |
| Control | Maximum Glycemic Excursion | Day 2 24-48 hours of infusion set | 51.6 mg/dL | Standard Deviation 32 |
Secondary
Pain Tolerability of Hyaluronidase Injections
Patients recorded pain experience at the infusion site (at time of injection and pain each day of wear) in subject diaries on a 0-5 pain scale (0 = no pain and 5 = worst pain imaginable). The number of diary entries are presented by scale category.
Time frame: Up to 4 weeks
Population: Only participants in the Hyaluronidase injections group completed diary entries to track pain.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hyaluronidase | Pain Tolerability of Hyaluronidase Injections | 0 on 0-5 pain scale | 58 Diary entries |
| Hyaluronidase | Pain Tolerability of Hyaluronidase Injections | 1 on 0-5 pain scale | 34 Diary entries |
| Hyaluronidase | Pain Tolerability of Hyaluronidase Injections | 2 on 0-5 pain scale | 11 Diary entries |
| Hyaluronidase | Pain Tolerability of Hyaluronidase Injections | 3 on 0-5 pain scale | 4 Diary entries |
| Hyaluronidase | Pain Tolerability of Hyaluronidase Injections | 4 on 0-5 pain scale | 0 Diary entries |
| Hyaluronidase | Pain Tolerability of Hyaluronidase Injections | 5 on 0-5 pain scale | 0 Diary entries |