Type 1 DiabetesNCT00977808
Pilot Study of Closed-Loop Glucose Control in People With Type 1 Diabetes (BPK004)
A study testing Open-Loop in people with Type 1 Diabetes, run by University of Virginia at 1 site in United States.
Trial summary
This study plans to link two existing technologies, the insulin pump and the continuous glucose monitor (CGM), to essentially develop an artificial pancreas, i.e., closed-loop. This will be done using two continuous glucose monitors (CGMs), a computer containing an investigational control algorithm that uses glucose… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Open-Loop
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Feb 2009
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 21 years of age or older
- Have Type 1 Diabetes Mellitus as defined by American Diabetes Association criteria or judgment of physician for at least 2 years (including those who may also be treated with metformin, thiazolidinedione, exenatide, or pramlintide).
- Use of an insulin pump
- If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, have stability on the medication for at least 1 month prior to enrollment in the study
- Willingness to use lispro (Humalog) insulin for the duration of the inpatient study
- Demonstration of proper mental status and cognition for the study
Who cannot join
- Age <21
- Pregnancy
- Hematocrit <36% (females); <38% (males)
- Symptomatic coronary artery disease (e.g. history of myocardial infarction, history of acute coronary syndrome, history of therapeutic coronary intervention, history of coronary bypass or stenting procedure, stable or unstable angina, episode of chest pain of cardiac etiology with documented EKG changes, positive stress test or catheterization with coronary blockages >50%).
- Congestive heart failure
- History of a cerebrovascular event
Show all 20Show fewer
- Use of a medication that significantly impacts glucose metabolism (oral steroids)
- Atrial fibrillation
- Uncontrolled hypertension (resting blood pressure >140/90)
- History of a systemic or deep tissue infection with methicillin-resistant staph aureus or Candida albicans
- Use of a device that may pose electromagnetic compatibility issues and/or radiofrequency interference with the FreeStyle NavigatorTM CGM (implantable cardioverter-defibrillator, electronic pacemaker, neurostimulator, intrathecal pump, and cochlear implants)
- Active enrollment in another clinical trial
- Allergy or adverse reaction to lispro insulin
- Known adrenal gland problem, pancreatic tumor, or insulinoma
- Current alcohol abuse, substance abuse, or severe mental illness
- Retinopathy and renal failure
- Uncontrolled anxiety or panic disorder
- Known bleeding diathesis or dyscrasia
- Renal insufficiency (creatinine >1.5)
- Any comorbid condition affecting glucose metabolism
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22904
About this study
Official title: Pilot Study of Closed-Loop Glucose Control in People With Type 1 Diabetes(BPK004)
This study plans to link two existing technologies, the insulin pump and the continuous glucose monitor (CGM), to essentially develop an artificial pancreas, i.e., closed-loop. This will be done using two continuous glucose monitors (CGMs), a computer containing an investigational control algorithm that uses glucose information from the CGM to recommend insulin dosing, and an insulin pump. The purpose of this study is to test the ability of continuous glucose monitors together with an insulin pump and a mathematical formula to control blood sugar levels of people with type 1 diabetes.
The Closed-Loop control algorithm will:
Read more
- Suggest adequate insulin delivery for blood glucose control in steady state (overnight);
- Cover adequately with an insulin bolus the pre-set carbohydrate content of a breakfast.
If successful, this study will conceptually prove the feasibility of automated model-predictive closed-loop glucose control in T1DM.
Read the detailed description
Each patient had an outpatient screening evaluation, and two 22 h overnight hospital admissions separated by a 2- to 4-week waiting period. Each inpatient admission began at 15:00 and ended at 13:00 on the following day. Subjects ate dinners and lunches with carbohydrate content that was the same at admission 1 and admission 2 and had identical morning meals of Ensure Plus (Abbott Nutrition, Columbus, OH). Two days before each admission, two Freestyle Navigator CGM devices (Abbott Diabetes Care) continuous glucose monitors were applied to the patient to allow for stabilization of the sensors and for assessment of their performance.
During admission 1, open-loop control was used, with the subjects' usual insulin routine and their personal insulin pump. During admission 2, an OmniPod Insulin Management System (Insulet Corp.) was inserted and used for closed-loop control of blood glucose. Insulin lispro (Eli Lilly, Indianapolis, IN), chosen based on commercial assays available, was used during both inpatient admissions.
At the beginning of admission 2, one of the two CGM devices was designated as primary, and the closed-loop control algorithm used the data of that system, unless a problem was detected. At 17:00, the model-predictive control (MPC) was initiated in a data-collection mode, automatically receiving CGM data every minute. Administration of the predinner insulin bolus was overseen by the attending physician. MPC, closed-loop control began at 21:30 and continued until 12:00 the next day for a total of 14.5 h.
Per FDA restrictions, the algorithm did not automatically control the insulin pump. Instead, the algorithm suggested insulin boluses every 15 min, which, if accepted, were programmed into the insulin pump by the attending physician. This was done for safety reasons, allowing the physician to override insulin delivery suggestions at any time. Reference blood glucose (using a YSI Life Sciences or a Beckman glucose analyzer) was sampled every 30 min. The protocol required switching to more frequent 15 min reference blood glucose sampling if hypoglycemia occurred or was imminent. Fast-acting carbohydrate (glucose tablets or fruit juice) was given when reference blood glucose fell below 3.9 mmol/liter, regardless of the CGM readings.
- Conditions
- Type 1 Diabetes
- Being tested
- Closed-Loop, Model Predictive Control (MPC), Open-Loop
- Keywords
- Artificial pancreas, Closed-Loop control
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Closed-Loop, Model Predictive Control (MPC)Device
Subjects used the OmniPod Insulin Management System (Insulet Corp.) and Insulin lispro (Eli Lilly, Indianapolis, IN). MPC algorithm suggested insulin boluses every 15 min, which, if accepted, were programmed into the insulin pump by the attending physician. Otherwise, the admission remained the same as in the open-loop admission (i.e. meals, sleep, etc...).
Open-LoopDevice
This admission was to assess the subjects' level of glucose control and created a base to compare the performance of the closed-loop system. Subjects monitored their own blood glucose values and administer their basal/bolus as they would at home. Subjects used their own insulin pumps and Insulin lispro (Eli Lilly, Indianapolis, IN). Otherwise, the admission remained the same as in the closed-loop admission (i.e. meals, sleep, etc...).
| Study group | Role | What they receive |
|---|---|---|
| Closed-Loop Model Predictive Control (MPC) | Experimental | Insulin dosing was performed by a model-predictive control (MPC) algorithm. Receives: Device: Closed-Loop, Model Predictive Control (MPC) |
| Open-Loop | Placebo comparator | Insulin dosing was performed by the patient (using their normal routine and personal insulin pump) under a physician's supervision. Receives: Device: Open-Loop |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Hypoglycemic Episodes
Hypoglycemic events were defined as below 3.9 mmol/liter and the percentage of time within the range of 3.9 to 7.8 mmol/liter overnight (21:30 until 08:00) as measured by reference blood glucose (YSI or Beckman Glucose Analyzer).
Measured: Overnight (21:30 until 08:00)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2009 (estimated)
- Study startMay 2008
- Primary completionFeb 2009
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation
- Responsible party
- Principal investigator, Boris Kovatchev, PhD, University of Virginia
- Investigators
- Boris P Kovatchev, Ph.D., Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00977808
- Sponsor's protocol ID
- 12998
- Other IDs
- BPK004
- Status last verified
- Aug 2014
- First submitted
- 15 Sep 2009
- Last updated
- 4 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Kovatchev B, Cobelli C, Renard E, Anderson S, Breton M, Patek S, Clarke W, Bruttomesso D, Maran A, Costa S, Avogaro A, Dalla Man C, Facchinetti A, Magni L, De Nicolao G, Place J, Farret A. Multinational study of subcutaneous model-predictive closed-loop control in type 1 diabetes mellitus: summary of the results. J Diabetes Sci Technol. 2010 Nov 1;4(6):1374-81. doi: 10.1177/193229681000400611.
PubMed 21129332
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Closed-Loop Glucose Control in People With Type 1 Diabetes(BPK004)
- ClinicalTrials.gov ID
- NCT00977808
- Acronym / sponsor ID
- 12998
- Conditions
- Type 1 Diabetes
- Keywords
- Artificial pancreas, Closed-Loop control
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation
- Study start
- May 2008
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 16 Sep 2009 (estimated)
- Results
- Posted 25 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study plans to link two existing technologies, the insulin pump and the continuous glucose monitor (CGM), to essentially develop an artificial pancreas, i.e., closed-loop. This will be done using two continuous glucose monitors (CGMs), a computer containing an investigational control algorithm that uses glucose information from the CGM to recommend insulin dosing, and an insulin pump. The purpose of this study is to test the ability of continuous glucose monitors together with an insulin pump and a mathematical formula to control blood sugar levels of people with type 1 diabetes.
The Closed-Loop control algorithm will:
- Suggest adequate insulin delivery for blood glucose control in steady state (overnight);
- Cover adequately with an insulin bolus the pre-set carbohydrate content of a breakfast.
If successful, this study will conceptually prove the feasibility of automated model-predictive closed-loop glucose control in T1DM.
Detailed description
Each patient had an outpatient screening evaluation, and two 22 h overnight hospital admissions separated by a 2- to 4-week waiting period. Each inpatient admission began at 15:00 and ended at 13:00 on the following day. Subjects ate dinners and lunches with carbohydrate content that was the same at admission 1 and admission 2 and had identical morning meals of Ensure Plus (Abbott Nutrition, Columbus, OH). Two days before each admission, two Freestyle Navigator CGM devices (Abbott Diabetes Care) continuous glucose monitors were applied to the patient to allow for stabilization of the sensors and for assessment of their performance.
During admission 1, open-loop control was used, with the subjects' usual insulin routine and their personal insulin pump. During admission 2, an OmniPod Insulin Management System (Insulet Corp.) was inserted and used for closed-loop control of blood glucose. Insulin lispro (Eli Lilly, Indianapolis, IN), chosen based on commercial assays available, was used during both inpatient admissions.
At the beginning of admission 2, one of the two CGM devices was designated as primary, and the closed-loop control algorithm used the data of that system, unless a problem was detected. At 17:00, the model-predictive control (MPC) was initiated in a data-collection mode, automatically receiving CGM data every minute. Administration of the predinner insulin bolus was overseen by the attending physician. MPC, closed-loop control began at 21:30 and continued until 12:00 the next day for a total of 14.5 h.
Per FDA restrictions, the algorithm did not automatically control the insulin pump. Instead, the algorithm suggested insulin boluses every 15 min, which, if accepted, were programmed into the insulin pump by the attending physician. This was done for safety reasons, allowing the physician to override insulin delivery suggestions at any time. Reference blood glucose (using a YSI Life Sciences or a Beckman glucose analyzer) was sampled every 30 min. The protocol required switching to more frequent 15 min reference blood glucose sampling if hypoglycemia occurred or was imminent. Fast-acting carbohydrate (glucose tablets or fruit juice) was given when reference blood glucose fell below 3.9 mmol/liter, regardless of the CGM readings.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Closed-Loop Model Predictive Control (MPC) | Experimental | Device: Closed-Loop, Model Predictive Control (MPC)Insulin dosing was performed by a model-predictive control (MPC) algorithm. |
| Open-Loop | Placebo comparator | Device: Open-LoopInsulin dosing was performed by the patient (using their normal routine and personal insulin pump) under a physician's supervision. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 21 years of age or older
- Have Type 1 Diabetes Mellitus as defined by American Diabetes Association criteria or judgment of physician for at least 2 years (including those who may also be treated with metformin, thiazolidinedione, exenatide, or pramlintide).
- Use of an insulin pump
- If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, have stability on the medication for at least 1 month prior to enrollment in the study
- Willingness to use lispro (Humalog) insulin for the duration of the inpatient study
Key exclusion criteria (20 listed)
- Age <21
- Pregnancy
- Hematocrit <36% (females); <38% (males)
- Symptomatic coronary artery disease (e.g. history of myocardial infarction, history of acute coronary syndrome, history of therapeutic coronary intervention, history of coronary bypass or stenting procedure, stable or unstable angina, episode of chest pain of cardiac etiology with documented EKG changes, positive stress test or catheterization with coronary blockages >50%).
- Congestive heart failure
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 |
|---|---|---|
| Closed-Loop, Model Predictive Control (MPC)Subjects used the OmniPod Insulin Management System (Insulet Corp.) and Insulin lispro (Eli Lilly, Indianapolis, IN). MPC algorithm suggested insulin boluses every 15 min, which, if accepted, were programmed into the insulin pump by the attending physician. Otherwise, the admission remained the same as in the open-loop admission (i.e. meals, sleep, etc...). | Device | Closed-Loop Model Predictive Control (MPC) |
| Open-LoopThis admission was to assess the subjects' level of glucose control and created a base to compare the performance of the closed-loop system. Subjects monitored their own blood glucose values and administer their basal/bolus as they would at home. Subjects used their own insulin pumps and Insulin lispro (Eli Lilly, Indianapolis, IN). Otherwise, the admission remained the same as in the closed-loop admission (i.e. meals, sleep, etc...). | Device | Open-Loop |
Primary outcome
Occurrence of Hypoglycemic Episodes
Time frame: Overnight (21:30 until 08:00)
Hypoglycemic events were defined as below 3.9 mmol/liter and the percentage of time within the range of 3.9 to 7.8 mmol/liter overnight (21:30 until 08:00) as measured by reference blood glucose (YSI or Beckman Glucose Analyzer).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21129332Kovatchev B, Cobelli C, Renard E, Anderson S, Breton M, Patek S, Clarke W, Bruttomesso D, Maran A, Costa S, Avogaro A, Dalla Man C, Facchinetti A, Magni L, De Nicolao G, Place J, Farret A. Multinational study of subcutaneous model-predictive closed-loop control in type 1 diabetes mellitus: summary of the results. J Diabetes Sci Technol. 2010 Nov 1;4(6):1374-81. doi: 10.1177/193229681000400611.
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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.
Boris P Kovatchev, Ph.D. principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Open-Loop in people with Type 1 Diabetes, run by University of Virginia 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 6 inclusion and 20 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 4 Sep 2014. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Occurrence of Hypoglycemic Episodes (time frame: Overnight (21:30 until 08:00)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00977808, which also lists 1 linked publication.
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 4 Sep 2014.