Type 1 DiabetesEarly Phase 1NCT01945099
Acceleration of Insulin Action by Hyaluronidase During Closed-Loop Therapy
A Early Phase 1 study testing ePID closed loop system, hyaluronidase and Lispro-PH20 in people with Type 1 Diabetes, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 40 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- ePID closed loop system, hyaluronidase and Lispro-PH20
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to Jul 2016
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale University School of Medicine
New Haven, Connecticut, 06520
About this study
"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.
Read the 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.
- Conditions
- Type 1 Diabetes
- Being tested
- ePID closed loop system, hyaluronidase, Lispro-PH20
- Keywords
- diabetes, insulin,post prandial, closed loop, artificial pancreas, hyperglycemia
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ePID closed loop systemDevice
Insulin pump controlled by closed loop unit and algorithm
hyaluronidaseDrug
Also called rHuPH20
Lispro-PH20Drug
Also called insulin-hyaluronidase co-formulation
| Study group | Role | What they receive |
|---|---|---|
| ePID closed loop system without hyaluronidase | Active comparator | Hyaluronidase will not be given while subject uses ePID closed loop system Receives: 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 Receives: 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 Receives: Device: ePID closed loop system; Drug: Lispro-PH20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: during each admission for 3 consecutive study visit days
Secondary outcomes (1)
Peak post-prandial insulin levels following meals
Measured: during each admission for 3 consecutive study visit days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2013 (estimated)
- Study startSep 2013
- Primary completionDec 2015
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eda Cengiz, MD, MHS, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01945099
- Sponsor's protocol ID
- 1307012334
- Status last verified
- May 2022
- First submitted
- 17 Jul 2013
- Last updated
- 24 May 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acceleration of Insulin Action by Hyaluronidase During Closed-Loop Therapy
- ClinicalTrials.gov ID
- NCT01945099
- Acronym / sponsor ID
- 1307012334
- Conditions
- Type 1 Diabetes
- Keywords
- diabetes, insulin,post prandial, closed loop, artificial pancreas, hyperglycemia
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 18 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
"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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ePID closed loop system without hyaluronidase | Active comparator | Device: ePID closed loop systemHyaluronidase will not be given while subject uses ePID closed loop system |
| ePID closed loop system with hyaluronidase at infusion site | Experimental | Device: ePID closed loop system, Drug: hyaluronidaseHyaluronidase will be injected at insulin pump infusion site prior to the time that subject uses ePID closed loop system |
| ePID closed loop system with hyaluronidase co-formulation | Experimental | Device: ePID closed loop system, Drug: Lispro-PH20Hyaluronidase-insulin co-formulation will be used in study pump while subject uses ePID closed loop system |
Who may qualify
- Ages
- 12 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ePID closed loop systemInsulin pump controlled by closed loop unit and algorithm | Device | ePID closed loop system with hyaluronidase at infusion site, ePID closed loop system with hyaluronidase co-formulation, ePID closed loop system without hyaluronidase |
| hyaluronidaseAlso: rHuPH20 | Drug | ePID closed loop system with hyaluronidase at infusion site |
| Lispro-PH20Also: insulin-hyaluronidase co-formulation | Drug | ePID closed loop system with hyaluronidase co-formulation |
Primary outcome
Peak post-prandial venous glucose levels obtained after breakfast, lunch, and dinner between CL alone and CL+PH20preRx and CL+INS-PH20
Time frame: during each admission for 3 consecutive study visit days
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.
1 secondary outcome
Peak post-prandial insulin levels following meals
Time frame: during each admission for 3 consecutive study visit days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eda Cengiz, MD, MHS principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing ePID closed loop system, hyaluronidase and Lispro-PH20 in people with Type 1 Diabetes, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak post-prandial venous glucose levels obtained after breakfast, lunch, and dinner between CL alone and CL+PH20preRx and CL+INS-PH20 (time frame: during each admission for 3 consecutive study visit days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2022.