Acceleration of Insulin Action by Hyaluronidase During Closed-Loop Therapy

NCT01945099 | Completed Early Phase 1

• 1 other identifier: 1307012334
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Keywords

diabetes, insulin,post prandial, closed loop, artificial pancreas, hyperglycemia

Outcome Measures

Primary Outcomes (1)

• 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.

  during each admission for 3 consecutive study visit days

Secondary Outcomes (1)

• Peak post-prandial insulin levels following meals

  during each admission for 3 consecutive study visit days

Other Outcomes (1)

• Area Under Curve meal-related insulin excursion following meals

  during each admission for 3 of the study days

Study Arms (3)

ePID closed loop system without hyaluronidase

ACTIVE COMPARATOR

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

Device: ePID closed loop system

ePID closed loop system with hyaluronidase at infusion site

EXPERIMENTAL

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

Device: ePID closed loop system; Drug: hyaluronidase

ePID closed loop system with hyaluronidase co-formulation

EXPERIMENTAL

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

Device: ePID closed loop system; Drug: Lispro-PH20

Interventions

ePID closed loop system DEVICE

Insulin pump controlled by closed loop unit and algorithm

ePID closed loop system with hyaluronidase at infusion site; ePID closed loop system with hyaluronidase co-formulation; ePID closed loop system without hyaluronidase

hyaluronidase DRUG

Also known as: rHuPH20

ePID closed loop system with hyaluronidase at infusion site

Lispro-PH20 DRUG

Also known as: insulin-hyaluronidase co-formulation

ePID closed loop system with hyaluronidase co-formulation

Eligibility Criteria

• Age: 12 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Hyperglycemia

Interventions

Hyaluronoglucosaminidase

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases

Study Officials

• Eda Cengiz, MD, MHS

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2013
• First Posted: September 18, 2013
• Study Start: September 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: July 1, 2016
• Last Updated: May 24, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)