Hyaluronidase Effect on Infusion Set Life

Study Overview
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Brief Summary
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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
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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.

Official Title
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Evaluation of Glucose Sensor and Insulin Infusion Set Failures: Hyaluronidase Study

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Hyaluronidase
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of type 1 diabetes for at least one year and using an insulin pump for at least 3 months Total daily insulin dose of at least 0.4 units/kg/day The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed. Age 12 to 45 years Hemoglobin A1c level less than or equal to 10% 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 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). Willingness to eat the same breakfast each morning for the first two weeks of the study Willing to take two 500mg tablets of Tylenol Regular Strength and monitor glucose levels at ½, 1, 2, 4, 6, and 8 hours later. For females, not currently known to be pregnant An understanding of and willingness to follow the protocol and sign the informed consent Must be able to understand spoken or written English Exclusion Criteria: Diabetic ketoacidosis in the past 6 months Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months prior to enrollment Known tape allergies Current treatment for a seizure disorder Cystic fibrosis Active infection A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples: Inpatient psychiatric treatment in the past 6 months for either the subject or the subject's primary care giver (i.e., parent or guardian) Presence of a known adrenal disorder 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 Abuse of alcohol Use of an OmniPod insulin infusion pump Pregnant or lactating females

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 45 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyaluronidase, Then Control<br>Participants assigned to active treatment arm (Hylenex) for weeks 1 and 3. On weeks 1 and 3 (Hyaluronidase weeks) subjects injected 1 milliliter (ml) Hyaluronidase (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear. On weeks 2 and 4 (control weeks) no Hyaluronidase was administered. | Drug: Hyaluronidase<br>* 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.<br>* Other names: Hylenex;Other: Control<br>* No hyaluronidase administered into insulin infusion set.<br>|
| Experimental: Control, Then Hyaluronidase<br>Participants were first assigned to the control arm. They received active treatment (Hyaluronidase) on weeks 2 and 4. On weeks 1 and 3 (control weeks) no Hyaluronidase was administered. On weeks 2 and 4 (Hyaluronidase weeks) subjects injected 1 milliliter (ml) Hyluronidase (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear. | Drug: Hyaluronidase<br>* 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.<br>* Other names: Hylenex;Other: Control<br>* No hyaluronidase administered into insulin infusion set.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 24 hours post infusion | 
| 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. | Up to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Continuous glucose monitor, hyaluronidase, infusion sets, insulin pump