Integration of Continuous Glucose Monitoring Into a BiHormonal Closed-Loop Artificial Pancreas

NCT ID: NCT01161862

Last Updated: 2017-11-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-31

Study Completion Date

2013-06-30

Brief Summary

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The investigators hypothesize that our closed-loop glucose-control system can provide BG control in subjects with type 1 diabetes using the estimated BG signal from a CGM as the input signal to the controller.

Detailed Description

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To test the safety and efficacy of our control system in the bi-hormonal configuration in regulating BG in adults (18 years of age or older) and in children (12-17 years of age) with type 1 diabetes based on interstitial-fluid (ISF) glucose data from a CGM. Experiments will be 51 hours in length incorporating 6 meals and two (night) sleep periods. In order to evaluate the effect of exercise on BG control, the last 48 hours of the experiment will be divided into two 24 hour blocks, the second of which will contain a period of structured exercise near the beginning of the block.

Conditions

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Diabetes Mellitus

Keywords

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Closed-loop Artificial pancreas Bi-hormonal Insulin Glucagon Diabetes mellitus type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Bi-hormonal with meal-priming bolus

The first meal-priming bolus was solely based on weight (0.05 U/kg), after which meal-priming boluses were automatically adapted by the control system online targeting 75% of the anticipated insulin needed in the first four hours after the start of the meal

Group Type EXPERIMENTAL

Bi-hormonal (insulin and glucagon) artificial pancreas

Intervention Type DEVICE

Subjects wore a bionic pancreas consisting of a continuous glucose monitor, an insulin pump and a glucagon pump

Bi-hormonal without meal-priming bolus

The insulin controller was entirely reactive to CGMG; there were no meal priming boluses and no meal announcements

Group Type EXPERIMENTAL

Bi-hormonal (insulin and glucagon) artificial pancreas

Intervention Type DEVICE

Subjects wore a bionic pancreas consisting of a continuous glucose monitor, an insulin pump and a glucagon pump

Interventions

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Bi-hormonal (insulin and glucagon) artificial pancreas

Subjects wore a bionic pancreas consisting of a continuous glucose monitor, an insulin pump and a glucagon pump

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Age 12 years or older with clinical type 1 diabetes for at least one year
* Weight \> 41 kg
* Otherwise healthy (mild chronic disease allowed if well controlled)
* Diabetes managed using an insulin infusion pump and rapid- or very-rapid-acting insulins
* Body mass index (BMI) between 20 and 35 for subjects \>18 years of age or BMI between the 5th and 95th percentile for age for subjects \< 18 years of age
* Total daily dose (TDD) of insulin that is \< 1 U/kg
* Stimulated C-peptide \< 0.1 nmol/L at 90 minutes after liquid mixed meal by DCCT protocol
* Hemoglobin A1c \<= 9%
* Prescription medication regimen stable for 1 month

Exclusion Criteria

* Unable to provide informed consent for subjects \> 18 years of age or unable to provide assent if \< 18 years of age
* Unable to comply with study procedures
* Current participation in another diabetes-related clinical trial other than one that is primarily observational in nature. Potential subjects enrolled in trials of passive monitoring equipment are not excluded.
* Anemia (HCT less than normal for age and sex)
* Alanine aminotransferase \> 3 fold above upper limit of normal
* Untreated or inadequately treated hyperthyroidism or hypothyroidism
* Pregnancy
* Renal insufficiency (creatinine clearance ≤ 50 ml/min)
* Any known history of coronary artery disease
* Abnormal EKG including, but not limited to evidence of active ischemia, prior myocardial infarction, proximal LAD critical stenosis (Wellen's sign), arrhythmia, tachycardia, and prolonged QT interval (\> 440 ms)
* Congestive heart failure
* History of TIA or stroke
* Acute illness or exacerbation of chronic illness
* History of seizures
* History of pheochromocytoma (fractionated metanephrines will be tested in patients with history suggestive of pheochromocytoma)
* 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 (intake averaging \> 3 drinks daily in last 30 days) or substance abuse (any use within the last 6 months of controlled substances without a prescription)
* Untreated or inadequately treated mental illness (indicators would include symptoms such as psychosis, hallucinations, mania, and any psychiatric hospitalization in the last year)
* Impaired cognition or altered mental status.
* Hypertension (blood pressure \> 140/90 or \> 95% for age, height and weight in subjects \< 18 years of age) at the time of screening
* Use of medications that reduce gastric motility (e.g. narcotics, anti-spasmodics, anticholinergics).
* Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference
* Use non-insulin, injectable anti-diabetic medications
* History of adverse reaction to glucagon (including allergy) besides nausea and vomiting.
* Established history of latex, adhesive, or tape allergy
* Inadequate venous access
* History of allergy to aspirin or any history of aspirin intolerance, including Reye syndrome, or gastric ulcer or bleeding associated with salicylates
* Blood dyscrasia or bleeding diathesis, such as hemophilia, Von Willebrands disorder, and idiopathic thrombocytopenic purpura (ITP)
* Peptic ulcer
* Unable to perform 30 minutes of moderate exercise on a treadmill or exercise bicycle
* Unable or unwilling to discontinue dietary supplements for at least 2 weeks prior to each CRC admission
* History of celiac disease
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Massachusetts General Hospital

OTHER

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role collaborator

The Leona M. and Harry B. Helmsley Charitable Trust

OTHER

Sponsor Role collaborator

Boston University Charles River Campus

OTHER

Sponsor Role lead

Responsible Party

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Edward R. Damiano

Associate Professor of Biomedical Engineering

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Steven J Russell, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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Damiano ER, El-Khatib FH, Zheng H, Nathan DM, Russell SJ. A comparative effectiveness analysis of three continuous glucose monitors. Diabetes Care. 2013 Feb;36(2):251-9. doi: 10.2337/dc12-0070. Epub 2012 Dec 28.

Reference Type DERIVED
PMID: 23275350 (View on PubMed)

Russell SJ, El-Khatib FH, Nathan DM, Magyar KL, Jiang J, Damiano ER. Blood glucose control in type 1 diabetes with a bihormonal bionic endocrine pancreas. Diabetes Care. 2012 Nov;35(11):2148-55. doi: 10.2337/dc12-0071. Epub 2012 Aug 24.

Reference Type DERIVED
PMID: 22923666 (View on PubMed)

Related Links

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Other Identifiers

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1R01DK085633-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H-29293

Identifier Type: -

Identifier Source: org_study_id