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Acceleration of Insulin Action by Hyaluronidase During Closed-Loop Therapy

Primary Purpose

Type 1 Diabetes

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
ePID closed loop system
hyaluronidase
Lispro-PH20
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring diabetes, insulin,post prandial, closed loop, artificial pancreas, hyperglycemia

Eligibility Criteria

12 Years - 40 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. age 12-40 years
  2. clinical diagnosis of T1D based on ADA criteria or presence of DKA at diagnosis (formal antibody and/or genetic testing will not be required)
  3. duration of T1D ≥ 1 year
  4. HbA1c ≤ 9 %
  5. Treated with CSII for at least 3 months
  6. Body weight > 37 kg (to accommodate phlebotomy)
  7. Normal hematocrit
  8. Normal creatinine
  9. Not pregnant or lactating, and for female subjects of reproductive potential, are abstinent or are consistently using barrier or hormonal methods of contraception

Exclusion Criteria:

  1. Insulin resistant (defined as requiring > 2 units/kg/day at time of study enrollment
  2. Previous allergic reaction to PH20
  3. Inability to comprehend written or spoken English
  4. Presence of any medical or psychiatric disorder that may interfere with subject safety or study conduct
  5. Use of any medications (besides insulin) known to affect blood glucose levels, including oral or other systemic glucocorticoid therapy. Inhaled, intranasal, or rectal corticosteroid use is allowed along as not given within 4 weeks of admission to the HRU. Use of topical glucocorticoids is allowable as long as affected skin area does not overlap with study device sites. Subjects using herbal supplements will be excluded, due to the unknown effects of these supplements on glucose control
  6. Use of furosemide, benzodiazepines or phenytoin during the study
  7. History of poor wound healing, heat sensitivity, or diminished skin integrity.
  8. History of hypoglycemic seizure within last 3 months
  9. Anemic (low hematocrit), or evidence of renal insufficiency (elevated serum creatinine)
  10. Female subjects who are pregnant, lactating, or unwilling to be tested for pregnancy
  11. Subjects unable to give consent / permission / assent

Sites / Locations

  • Yale University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

ePID closed loop system without hyaluronidase

ePID closed loop system with hyaluronidase at infusion site

ePID closed loop system with hyaluronidase co-formulation

Arm Description

Hyaluronidase will not be given while subject uses ePID closed loop system

Hyaluronidase will be injected at insulin pump infusion site prior to the time that subject uses ePID closed loop system

Hyaluronidase-insulin co-formulation will be used in study pump while subject uses ePID closed loop system

Outcomes

Primary Outcome Measures

Peak post-prandial venous glucose levels obtained after breakfast, lunch, and dinner between CL alone and CL+PH20preRx and CL+INS-PH20
Peak post-prandial plasma glucose excursions (mg/dL) after breakfast, lunch, and dinner on days #2, #3 and #4. One day with hylauronidase pre-treated insulin infusion site site, other day with hyaluronidase-rapid acting insulin co-formulation infusion and control day with rapid acting insulin only.

Secondary Outcome Measures

Peak post-prandial insulin levels following meals

Full Information

First Posted
July 17, 2013
Last Updated
May 17, 2022
Sponsor
Yale University
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1. Study Identification

Unique Protocol Identification Number
NCT01945099
Brief Title
Acceleration of Insulin Action by Hyaluronidase During Closed-Loop Therapy
Official Title
Acceleration of Insulin Action by Hyaluronidase During Closed-Loop Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
"Closed loop artificial pancreas" systems have been under development for the control of blood sugars in those living with diabetes. These systems consist of a continuous glucose sensor, which sends a signal to a computer program that automatically determines how much insulin to give. The computer program then tells an insulin pump to deliver the insulin. While such systems have been tested under a number of conditions, post-meal blood sugars are difficult to control. Specifically, we will be looking to see if using hyaluronidase improves the ability of the closed loop artificial pancreas to better respond to meal related highs and lows.
Detailed Description
To investigate the effect of rHuPH20, an adjuvant that accelerates the dispersion and absorption of subcutaneously injected or infused drugs, on mitigating post-prandial blood glucose excursions when injected separately or co-formulated with insulin during closed-loop therapy for youth and young adults with type 1 diabetes. Closed-loop control will be achieved using external subcutaneous real-time continuous glucose monitoring and continuous subcutaneous insulin infusion along with a computerized algorithm to link these two processes. Specific Aim 1: To examine whether co-formulation rHuPH20 with analog insulin (INS-PH20)or, alternately, pre-administration of rHuPH20 (PH20-preRx) at the time of infusion set placement prior to initiation of closed-loop (CL) insulin delivery will reduce peak-postprandial glucose concentrations and total glucose area under the curve of the meal excursions in short term inpatient experiments. Specific Aim 2: To investigate whether accelerated insulin absorption by rHuPH20, delivered as described above, will also result in a reduction of late-post-prandial hyperinsulinemia and late post-prandial hypoglycemia during CL insulin delivery. Specific Aim 3: To compare the insulin accelerator effect of INS-PH20 to that of PH20-preRx, based on post prandial glucose excursions during closed-loop therapy We hypothesize that; utilization of PH20 either as a separate injection (PH20-preRx) or in a co-formulation with insulin (INS-PH20) during CL therapy will reduce peak-postprandial glucose concentrations and total glucose under the curve of the meal excursion as compared to CL control without any intervention, and we propose that the use of PH20-preRx and INS-PH20 will be well tolerated when delivered in youth and young adults in a closed-loop setting.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
diabetes, insulin,post prandial, closed loop, artificial pancreas, hyperglycemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ePID closed loop system without hyaluronidase
Arm Type
Active Comparator
Arm Description
Hyaluronidase will not be given while subject uses ePID closed loop system
Arm Title
ePID closed loop system with hyaluronidase at infusion site
Arm Type
Experimental
Arm Description
Hyaluronidase will be injected at insulin pump infusion site prior to the time that subject uses ePID closed loop system
Arm Title
ePID closed loop system with hyaluronidase co-formulation
Arm Type
Experimental
Arm Description
Hyaluronidase-insulin co-formulation will be used in study pump while subject uses ePID closed loop system
Intervention Type
Device
Intervention Name(s)
ePID closed loop system
Intervention Description
Insulin pump controlled by closed loop unit and algorithm
Intervention Type
Drug
Intervention Name(s)
hyaluronidase
Other Intervention Name(s)
rHuPH20
Intervention Type
Drug
Intervention Name(s)
Lispro-PH20
Other Intervention Name(s)
insulin-hyaluronidase co-formulation
Primary Outcome Measure Information:
Title
Peak post-prandial venous glucose levels obtained after breakfast, lunch, and dinner between CL alone and CL+PH20preRx and CL+INS-PH20
Description
Peak post-prandial plasma glucose excursions (mg/dL) after breakfast, lunch, and dinner on days #2, #3 and #4. One day with hylauronidase pre-treated insulin infusion site site, other day with hyaluronidase-rapid acting insulin co-formulation infusion and control day with rapid acting insulin only.
Time Frame
during each admission for 3 consecutive study visit days
Secondary Outcome Measure Information:
Title
Peak post-prandial insulin levels following meals
Time Frame
during each admission for 3 consecutive study visit days
Other Pre-specified Outcome Measures:
Title
Area Under Curve meal-related insulin excursion following meals
Time Frame
during each admission for 3 of the study days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: age 12-40 years clinical diagnosis of T1D based on ADA criteria or presence of DKA at diagnosis (formal antibody and/or genetic testing will not be required) duration of T1D ≥ 1 year HbA1c ≤ 9 % Treated with CSII for at least 3 months Body weight > 37 kg (to accommodate phlebotomy) Normal hematocrit Normal creatinine Not pregnant or lactating, and for female subjects of reproductive potential, are abstinent or are consistently using barrier or hormonal methods of contraception Exclusion Criteria: Insulin resistant (defined as requiring > 2 units/kg/day at time of study enrollment Previous allergic reaction to PH20 Inability to comprehend written or spoken English Presence of any medical or psychiatric disorder that may interfere with subject safety or study conduct Use of any medications (besides insulin) known to affect blood glucose levels, including oral or other systemic glucocorticoid therapy. Inhaled, intranasal, or rectal corticosteroid use is allowed along as not given within 4 weeks of admission to the HRU. Use of topical glucocorticoids is allowable as long as affected skin area does not overlap with study device sites. Subjects using herbal supplements will be excluded, due to the unknown effects of these supplements on glucose control Use of furosemide, benzodiazepines or phenytoin during the study History of poor wound healing, heat sensitivity, or diminished skin integrity. History of hypoglycemic seizure within last 3 months Anemic (low hematocrit), or evidence of renal insufficiency (elevated serum creatinine) Female subjects who are pregnant, lactating, or unwilling to be tested for pregnancy Subjects unable to give consent / permission / assent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eda Cengiz, MD, MHS
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Acceleration of Insulin Action by Hyaluronidase During Closed-Loop Therapy

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