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Hyaluronidase Effect on Infusion Set Life

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ClinicalTrials.gov Identifier: NCT02199028
Recruitment Status : Completed
First Posted : July 24, 2014
Last Update Posted : April 2, 2015
Sponsor:
Collaborator:
University of Colorado Denver School of Medicine Barbara Davis Center
Information provided by (Responsible Party):
Bruce A. Buckingham, Stanford University

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. The investigators will also assess the accuracy of the Dexcom G4 Platinum (G4P) sensors with extended sensor wear beyond the 7 day FDA approved time frame.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Drug: Hyaluronidase Phase 2 Phase 3

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.

You are invited to participate in a research study 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. Eligible subjects are those with type 1 diabetes who wear an insulin pump.

Thirty subjects will be enrolled. Fifteen patients from each of the two sites: Stanford University and University of Colorado.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Glucose Sensor and Insulin Infusion Set Failures: Hyaluronidase Study
Study Start Date : July 2014
Actual Primary Completion Date : March 2015
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Hyaluronidase
Infuse 1mL Hyaluronidase at time of infusion set placement and again on Day 3
Drug: Hyaluronidase
If assigned to hyaluronidase week, subjects will inject 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set. They will then give a catheter fixed prime of 0.7 cc to clear the infusion set of hyaluronidase. On the morning of day 3 during a Hyaluronidase week, a second dose of 1ml Hylenex (150 units/1ml) will be injected through the catheter hub prior to breakfast using the Duo Infusion Set Tubing. They will then reconnect their pump catheter and give a fixed prime of 0.7 cc to clear the infusion set of hyaluronidase.
Other Name: Hylenex

No Intervention: Control
Subjects will not receive Hyaluronidase during this week



Primary Outcome Measures :
  1. Sensor and infusion set failure [ Time Frame: participants will be followed for 4 weeks as outpatients, including 5 visits to CTRU (prior to enrollment and after each week) ]
    To generate data sets with sensor and infusion set failure. These data will generate 120 weeks of infusion set data (and we anticipate 72 infusion site failures), and 120 "two week" sensor wears (with an anticipated 72 sensor failures). This will provide sufficient data sets for the initial development of prediction models to detect sensor and infusion set failure to be used in closed-loop artificial pancreas algorithms.


Secondary Outcome Measures :
  1. Hyaluronidase effects on glucodynamics [ Time Frame: participants will be followed for 4 weeks as outpatients, including 5 visits to CTRU (prior to enrollment and after each week) ]
    Evaluate postprandial glucodynamic parameters for the breakfast meal using sensor glucose values for each day of infusion set wear: 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 versus without hyaluronidase.

  2. Effect of hyaluronidase on glycemic control [ Time Frame: participants will be followed for 4 weeks as outpatients, including 5 visits to CTRU (prior to enrollment and after each week) ]
    Evaluate average daily blood glucose (mean +/- standard deviation and median +/- IQR) for each day of infusion set wear with and without hyaluronidase

  3. Effect of Tylenol on Dexcom G4 sensor glucose values [ Time Frame: Eight hours during week 4 of enrollment ]
    Once during week 4 at breakfast, we will ask subjects to take acetaminophen in the form of two 500 mg Tylenol Regular Strength tablets and then obtain meter readings at ½ hour, 1 hour, and then 2, 4, 6, and 8 hours after the Tylenol ingestion. During this time they should not use any data from their Dexcom G4P sensors for diabetes management decisions. Subjects will be given a log to documents their blood glucose values.

  4. Evaluate tolerability of hyaluronidase injections [ Time Frame: participants will be followed for 4 weeks as outpatients, including 5 visits to CTRU (prior to enrollment and after each week) ]
    1. Pain at time of injection (0-5 pain scale)
    2. Infusion site erythema each day of wear (measured in mm)
    3. Infusion site induration each day of wear (measured in mm)
    4. Pain at infusion site each day of wear (0-5 pain scale)

  5. Evaluate insulin precipitation in infusion site cannulas via DTZ staining [ Time Frame: After each of the 4 weeks, participants will provide their infusion set catheters for analysis ]
    We plan to stain insulin infusion set catheter tip with diphenylthiocarbazone (DTZ) to evaluate for insulin precipitation as a potential cause of infusion set failure. DTZ is a chelating ligand that forms photochromic complexes with a variety of metals. It is known to selectively stain pancreatic cells crimson read because of the large amount of zinc in the islets. Catheters will be photographed using a Zeiss Axiovert 200 digital microscope, and photographs of the catheter staining will be analyzed using software for image analysis.



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Ages Eligible for Study:   12 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02199028


Locations
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United States, California
Stanford University
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
University of Colorado Denver School of Medicine Barbara Davis Center
Investigators
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Principal Investigator: Bruce A Buckingham, MD Stanford University

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bruce A. Buckingham, Principle Investigator, Stanford University
ClinicalTrials.gov Identifier: NCT02199028     History of Changes
Other Study ID Numbers: 28949
JDRF 17-2013/471 ( Other Grant/Funding Number: JDRF )
First Posted: July 24, 2014    Key Record Dates
Last Update Posted: April 2, 2015
Last Verified: September 2014

Keywords provided by Bruce A. Buckingham, Stanford University:
hyaluronidase
infusion sets
insulin pump
Continuous glucose monitor

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs