Closed-loop Glucose Control for Automated Management of Type 1 Diabetes

October 24, 2017 updated by: Edward R. Damiano, Boston University Charles River Campus
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria (type 1 diabetic subjects):

  • 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
  • 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

Inclusion Criteria (non-diabetic subjects):

  • 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)

Exclusion Criteria (all subjects):

  • 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
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Closed-loop
Type 1 diabetic subjects under closed-loop blood glucose control
Device: Closed-loop
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Average Blood Glucose Over the Closed-loop Control Period
Time Frame: 24 hours
24 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Time Spent Within 70-180 mg/dl
Time Frame: 24 hours
24 hours
Peak Hyperglycemia Following Each Meal
Time Frame: After each of 3 meals
After each of 3 meals
Percentage of Time Spent in Hyperglycemia (BG> 180 mg/dl) After Meals
Time Frame: After each of 3 meals
After each of 3 meals
Percentage of Peak Post-prandial Hyperglycemias < 180 mg/dl (ADA Target)
Time Frame: 24 hours
24 hours
Percentage of Time Spent With BG < 70 mg/dl
Time Frame: 24 hours
24 hours
Number of Hypoglycemic Events
Time Frame: 24 hours
This outcome captures the number of hypoglycemic events that occurred throughout the entire study
24 hours
Nadir Blood Glucose Level for Each Hypoglycemic Event
Time Frame: 24 hours
24 hours
Percentage of Time Spent With BG > 180 mg/dl
Time Frame: 24 hours
24 hours
Total Insulin Dose
Time Frame: 24 hours
24 hours
Glucagon T-max
Time Frame: 24 hours
Time to maximum peak glucagon concentration
24 hours
Total Glucagon Dose
Time Frame: 24 hours
24 hours
Blood Glucagon Levels
Time Frame: 24 hours
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
24 hours
Number of Carbohydrate Interventions
Time Frame: 24 hours
24 hours
Number of Participants Achieving a Stable Glucose Response to Insulin Dosing
Time Frame: 24 hours
24 hours
Number of Participants Achieving a Stable Glucose Response to Insulin Dosing Around Idle Times Prior to Meals
Time Frame: 24 hours
24 hours
Accuracy of the Continuous Glucose Monitor (CGM) Using Blood Glucose Measurement as the Standard
Time Frame: 24 hours
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
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
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
24 hours
Sensitivity for Hypo- and Hyperglycemia of the CGM Devices Using the BG Measurement as the Standard
Time Frame: 24 hours
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
24 hours
Set Point Using CGM Data as the Input to the Controller for Future Studies
Time Frame: 24 hours
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.
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
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boston University Charles River Campus

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Massachusetts General Hospital
Juvenile Diabetes Research Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Steven J Russell, M.D., Ph.D., Massachusetts General Hospital
  • Principal Investigator: Edward Damiano, Ph.D., Boston University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 29, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 18, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 25, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2007P-000101
  • H-27207
  • SPID#0813

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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