Type 1 DiabetesNCT00811317
Closed-loop Glucose Control for Automated Management of Type 1 Diabetes
A study testing Closed-loop in people with Type 1 Diabetes, run by Boston University Charles River Campus at 1 site in United States.
Trial summary
We hypothesize that our integrated closed-loop glucose-control system can provide effective, tight, and safe blood glucose (BG) control in type 1 diabetes, thereby establishing the feasibility of closed-loop BG control. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Closed-loop
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Oct 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Clinical type 1 diabetes for at least five years
- Otherwise healthy (mild chronic disease allowed if well controlled)
- Diabetes managed using an insulin infusion pump
- Body mass index (BMI) between 20 and 31
- Total daily dose (TDD) of insulin ≤ 1 U/kg and ≤ 100 U/day
Show all 16Show fewer
- Post-prandial C-peptide < 0.1 nmol/L at 90 minutes in a mixed meal (Sustacal) tolerance test by the DCCT method
- Hemoglobin A1c less than or equal to 8.5%
- Prescription medication regimen stable for at least 1 month
- Age 18 years or older
- No personal history of diabetes, impaired fasting glucose, or impaired glucose tolerance
- No personal history of pancreatic disease
- Not taking medication that may affect glucose, insulin, or glucagon dynamics
- Otherwise healthy (mild chronic disease allowed if well controlled)
- Body mass index (BMI) between 20 and 31
- Normal 75 g oral glucose tolerance test (fasting, 1 hour, and 2 hour measurements)
Who cannot join
- Unable to provide informed consent or are unable to comply with study procedures
- Current participation in another clinical trial
- Anemia (HCT or hemoglobin less than normal for sex)
- Elevated alanine aminotransferase (ALT > 3 fold above upper limit of normal)
- Untreated or inadequately treated hyperthyroidism or hypothyroidism (abnormal TSH or free T4)
- Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception
Show all 29Show fewer
- Progressive or proliferative diabetic retinopathy (subjects with mild, non-proliferative background retinopathy or stable disease previously treated with photocoagulation are not excluded).
- Renal insufficiency (creatinine clearance estimated by Cockcroft-Gault equation of ≤ 50 ml/min)
- Any known history or symptoms of coronary artery disease.
- Abnormal EKG
- Congestive heart failure
- History of TIA or stroke within preceding 6 months
- Acute illness or exacerbation of chronic illness at the time of the study procedure
- Change in medication regimen in the 30 days prior to enrollment
- History of seizures
- History of pheochromocytoma
- Abnormal plasma fractionated metanephrines
- History of adrenal disease or tumor
- History of pancreatic tumor, including insulinoma
- History of impaired gastric motility or gastroparesis requiring pharmacological or surgical treatment
- Current alcohol abuse (> 3 drinks daily) or substance abuse (any use within the last 6 months of illegal drugs)
- Severe mental illness (schizophrenia, bipolar disease, inadequately treated depression, or any psychiatric hospitalization in the last year)
- Impaired cognition or altered mental status.
- Hypertension (blood pressure > 140/90) at the time of screening
- Use of medications that reduce gastric motility
- Electrically powered implants that might be susceptible to RF interference
- Use non-insulin injectable anti-diabetic medications, inhaled insulin, or oral anti-diabetic medications
- History of adverse reaction to glucagon (including allergy) besides nausea and vomiting.
- Established history of latex, adhesive, tape allergy, inadequate venous access, history of allergy to or intolerance of aspirin.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
We hypothesize that our integrated closed-loop glucose-control system can provide effective, tight, and safe blood glucose (BG) control in type 1 diabetes, thereby establishing the feasibility of closed-loop BG control.
Read the detailed description
This study investigates the utility of an integrated closed-loop glucose-control system for regulating BG in type 1 diabetic subjects. The closed-loop system utilizes sub-cutaneous infusion or insulin and glucagon under the control of a computer algorithm. The only inputs to the algorithm are the subject weight and BG values measured every five minutes. Subjects will undergo up to three 27 hour GCRC admissions during which they will consume three standardized meals. Subject may participate in up to two closed-loop visits (with different insulin lispro pharmacokinetic parameter settings in the control algorithm) and some subjects will participate in open-loop visits. During the closed-loop admission BG will be controlled by the closed-loop system. During the open-loop visit subjects will regulate their own BG in the usual function using their insulin pumps. A small group of non-diabetic subjects will undergo a single 27 hour GCRC admission during which they will eat the same standardized meals. During all admission BG will be measured every 5 minutes and blood will be collected for measurement of insulin and glucagon levels every 10 minutes. During the closed-loop admission of diabetic subjects and the single admission of non-diabetic subjects, three commercially available continuous glucose monitoring devices will be worn. The data from these devices will later be compared to reference BG data.
- Conditions
- Type 1 Diabetes
- Being tested
- Closed-loop
- Keywords
- diabetes, glucose, hyperglycemia, hypoglycemia, insulin, glucagon, counter-regulation, closed-loop, feedback, control, dual-infusion, subcutaneous, automated, artificial pancreas, intensive insulin therapy
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Hyperglycemia, Hypoglycemia, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Closed-loopDevice
Computer algorithm developed by Firas El-Khatib and Edward Damiano at Boston University that controls sub-cutaneous infusion of insulin and glucagon to regulate blood glucose to target
| Study group | Role | What they receive |
|---|---|---|
| Closed-loop | Experimental | Type 1 diabetic subjects under closed-loop blood glucose control Receives: Device: Closed-loop |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Blood Glucose Over the Closed-loop Control Period
Measured: 24 hours
Secondary outcomes (22)
Percentage of Time Spent Within 70-180 mg/dl
Measured: 24 hours
Peak Hyperglycemia Following Each Meal
Measured: After each of 3 meals
Percentage of Time Spent in Hyperglycemia (BG> 180 mg/dl) After Meals
Measured: After each of 3 meals
Percentage of Peak Post-prandial Hyperglycemias < 180 mg/dl (ADA Target)
Measured: 24 hours
Percentage of Time Spent With BG < 70 mg/dl
Measured: 24 hours
Number of Hypoglycemic Events
This outcome captures the number of hypoglycemic events that occurred throughout the entire study
Measured: 24 hours
Nadir Blood Glucose Level for Each Hypoglycemic Event
Measured: 24 hours
Percentage of Time Spent With BG > 180 mg/dl
Measured: 24 hours
Total Insulin Dose
Measured: 24 hours
Glucagon T-max
Time to maximum peak glucagon concentration
Measured: 24 hours
Total Glucagon Dose
Measured: 24 hours
Blood Glucagon Levels
Measured: 24 hours
Average Glucose and Glycemic Variability (MAGE) During Closed Loop Control in Diabetic Subjects Compared to the Comparable 24-hour Period the Day Prior to Admission as Measured by Navigator CGM Data
Measured: 24 hours
Number of Carbohydrate Interventions
Measured: 24 hours
Number of Participants Achieving a Stable Glucose Response to Insulin Dosing
Measured: 24 hours
Number of Participants Achieving a Stable Glucose Response to Insulin Dosing Around Idle Times Prior to Meals
Measured: 24 hours
Accuracy of the Continuous Glucose Monitor (CGM) Using Blood Glucose Measurement as the Standard
Measuring the mean absolute relative difference (MARD) between the blood glucose measurement and CGM glucose readings, on three different CGM devices: Dexcom, Guardian and Navigator
Measured: 24 hours
Average Glucose and Glycemic Variability During Closed Loop Control in Diabetic Subjects Compared to the Comparable 24 Hour Period in Non-diabetic Subjects
Measured: 24 hours
Insulin and Glucagon Levels During the Closed-loop Admission as Compared to the Comparable 24 Hour Period During the Open Loop Admission of Diabetic Subjects
Measured: 24 hours
Sensitivity for Hypo- and Hyperglycemia of the CGM Devices Using the BG Measurement as the Standard
Mean absolute relative difference (MARD) of CGM and BG glucose readings in hypoglycemia (< 70 mg/dl) and hyperglycemia (>180 mg/dl) in three different CGM devices: Dexcom, Navigator and Guardian
Measured: 24 hours
Set Point Using CGM Data as the Input to the Controller for Future Studies
The algorithm in the Bionic Pancreas must have a pre-specified target glucose it is trying to achieve in order to make dosing decisions. Using data from this study, investigators planned to determine what an appropriate glucose target should be for future studies.
Measured: 24 hours
Insulin and Glucagon Levels During Closed Loop and Open Loop Admissions of Diabetic Subjects Compared to the Comparable 24 Hour Period During the Admission of Non-diabetic Subject
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2008 (estimated)
- Study startMay 2008
- Primary completionOct 2009
- Study completionOct 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 (3)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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston University Charles River Campus
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital, Juvenile Diabetes Research Foundation
- Responsible party
- Principal investigator, Edward R. Damiano, Boston University
- Investigators
- Steven J Russell, M.D., Ph.D., Study director, Massachusetts General HospitalEdward Damiano, Ph.D., Principal investigator, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00811317
- Sponsor's protocol ID
- 2007P-000101
- Other IDs
- H-27207, SPID#0813
- Status last verified
- Oct 2017
- First submitted
- 29 May 2008
- Last updated
- 25 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes
Publications
El-Khatib FH, Jiang J, Gerrity RG, Damiano ER. Pharmacodynamics and stability of subcutaneously infused glucagon in a type 1 diabetic Swine model in vivo. Diabetes Technol Ther. 2007 Apr;9(2):135-44. doi: 10.1089/dia.2006.0006.
PubMed 17425438El-Khatib FH, Jiang J, Damiano ER. Adaptive closed-loop control provides blood-glucose regulation using dual subcutaneous insulin and glucagon infusion in diabetic Swine. J Diabetes Sci Technol. 2007 Mar;1(2):181-92. doi: 10.1177/193229680700100208.
PubMed 19888405El-Khatib FH, Jiang J, Damiano ER. A feasibility study of bihormonal closed-loop blood glucose control using dual subcutaneous infusion of insulin and glucagon in ambulatory diabetic swine. J Diabetes Sci Technol. 2009 Jul 1;3(4):789-803. doi: 10.1177/193229680900300428.
PubMed 20144330
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Closed-loop Glucose Control for Automated Management of Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT00811317
- Acronym / sponsor ID
- 2007P-000101
- Conditions
- Type 1 Diabetes
- Keywords
- diabetes, glucose, hyperglycemia, hypoglycemia, insulin, glucagon, counter-regulation, closed-loop
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Boston University Charles River CampusUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital, Juvenile Diabetes Research Foundation
- Study start
- May 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 18 Dec 2008 (estimated)
- Results
- Posted 25 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We hypothesize that our integrated closed-loop glucose-control system can provide effective, tight, and safe blood glucose (BG) control in type 1 diabetes, thereby establishing the feasibility of closed-loop BG control.
Detailed description
This study investigates the utility of an integrated closed-loop glucose-control system for regulating BG in type 1 diabetic subjects. The closed-loop system utilizes sub-cutaneous infusion or insulin and glucagon under the control of a computer algorithm. The only inputs to the algorithm are the subject weight and BG values measured every five minutes. Subjects will undergo up to three 27 hour GCRC admissions during which they will consume three standardized meals. Subject may participate in up to two closed-loop visits (with different insulin lispro pharmacokinetic parameter settings in the control algorithm) and some subjects will participate in open-loop visits. During the closed-loop admission BG will be controlled by the closed-loop system. During the open-loop visit subjects will regulate their own BG in the usual function using their insulin pumps. A small group of non-diabetic subjects will undergo a single 27 hour GCRC admission during which they will eat the same standardized meals. During all admission BG will be measured every 5 minutes and blood will be collected for measurement of insulin and glucagon levels every 10 minutes. During the closed-loop admission of diabetic subjects and the single admission of non-diabetic subjects, three commercially available continuous glucose monitoring devices will be worn. The data from these devices will later be compared to reference BG data.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Closed-loop | Experimental | Device: Closed-loopType 1 diabetic subjects under closed-loop blood glucose control |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age 18 years or older
- Clinical type 1 diabetes for at least five years
- Otherwise healthy (mild chronic disease allowed if well controlled)
- Diabetes managed using an insulin infusion pump
- Body mass index (BMI) between 20 and 31
Key exclusion criteria (29 listed)
- Unable to provide informed consent or are unable to comply with study procedures
- Current participation in another clinical trial
- Anemia (HCT or hemoglobin less than normal for sex)
- Elevated alanine aminotransferase (ALT > 3 fold above upper limit of normal)
- Untreated or inadequately treated hyperthyroidism or hypothyroidism (abnormal TSH or free T4)
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-loopComputer algorithm developed by Firas El-Khatib and Edward Damiano at Boston University that controls sub-cutaneous infusion of insulin and glucagon to regulate blood glucose to target | Device | Closed-loop |
Primary outcome
Average Blood Glucose Over the Closed-loop Control Period
Time frame: 24 hours
22 secondary outcomes
Percentage of Time Spent Within 70-180 mg/dl
Time frame: 24 hours
Peak Hyperglycemia Following Each Meal
Time frame: After each of 3 meals
Percentage of Time Spent in Hyperglycemia (BG> 180 mg/dl) After Meals
Time frame: After each of 3 meals
Percentage of Peak Post-prandial Hyperglycemias < 180 mg/dl (ADA Target)
Time frame: 24 hours
Percentage of Time Spent With BG < 70 mg/dl
Time frame: 24 hours
Number of Hypoglycemic Events
Time frame: 24 hours
Nadir Blood Glucose Level for Each Hypoglycemic Event
Time frame: 24 hours
Percentage of Time Spent With BG > 180 mg/dl
Time frame: 24 hours
Total Insulin Dose
Time frame: 24 hours
Glucagon T-max
Time frame: 24 hours
Total Glucagon Dose
Time frame: 24 hours
Blood Glucagon Levels
Time frame: 24 hours
Average Glucose and Glycemic Variability (MAGE) During Closed Loop Control in Diabetic Subjects Compared to the Comparable 24-hour Period the Day Prior to Admission as Measured by Navigator CGM Data
Time frame: 24 hours
Number of Carbohydrate Interventions
Time frame: 24 hours
Number of Participants Achieving a Stable Glucose Response to Insulin Dosing
Time frame: 24 hours
Number of Participants Achieving a Stable Glucose Response to Insulin Dosing Around Idle Times Prior to Meals
Time frame: 24 hours
Accuracy of the Continuous Glucose Monitor (CGM) Using Blood Glucose Measurement as the Standard
Time frame: 24 hours
Average Glucose and Glycemic Variability During Closed Loop Control in Diabetic Subjects Compared to the Comparable 24 Hour Period in Non-diabetic Subjects
Time frame: 24 hours
Insulin and Glucagon Levels During the Closed-loop Admission as Compared to the Comparable 24 Hour Period During the Open Loop Admission of Diabetic Subjects
Time frame: 24 hours
Sensitivity for Hypo- and Hyperglycemia of the CGM Devices Using the BG Measurement as the Standard
Time frame: 24 hours
Set Point Using CGM Data as the Input to the Controller for Future Studies
Time frame: 24 hours
Insulin and Glucagon Levels During Closed Loop and Open Loop Admissions of Diabetic Subjects Compared to the Comparable 24 Hour Period During the Admission of Non-diabetic Subject
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17425438El-Khatib FH, Jiang J, Gerrity RG, Damiano ER. Pharmacodynamics and stability of subcutaneously infused glucagon in a type 1 diabetic Swine model in vivo. Diabetes Technol Ther. 2007 Apr;9(2):135-44. doi: 10.1089/dia.2006.0006.
- Background: PubMed 19888405El-Khatib FH, Jiang J, Damiano ER. Adaptive closed-loop control provides blood-glucose regulation using dual subcutaneous insulin and glucagon infusion in diabetic Swine. J Diabetes Sci Technol. 2007 Mar;1(2):181-92. doi: 10.1177/193229680700100208.
- Background: PubMed 20144330El-Khatib FH, Jiang J, Damiano ER. A feasibility study of bihormonal closed-loop blood glucose control using dual subcutaneous infusion of insulin and glucagon in ambulatory diabetic swine. J Diabetes Sci Technol. 2009 Jul 1;3(4):789-803. doi: 10.1177/193229680900300428.
- Individual participant dataSharing planned: Yes
Related trials for Type 1 Diabetes
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
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.
Steven J Russell, M.D., Ph.D. study director
Massachusetts General Hospital
Edward Damiano, Ph.D. principal investigator
Boston University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Closed-loop in people with Type 1 Diabetes, run by Boston University Charles River Campus 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 16 inclusion and 29 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 25 Oct 2017. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Oct 2017). 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?
Average Blood Glucose Over the Closed-loop Control Period (time frame: 24 hours). 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 NCT00811317, which also lists 3 linked publications.
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 25 Oct 2017.