CL2: Integration of Continuous Glucose Monitoring Into a BiHormonal Closed-Loop Artificial Pancreas

• Sponsor: Boston University Charles River Campus (Other)
• Overall Status: Completed
• CT.gov ID: NCT01161862
• Collaborator: Massachusetts General Hospital (Other), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Juvenile Diabetes Research Foundation (Other), The Leona M. and Harry B. Helmsley Charitable Trust (Other)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus	Device: Bi-hormonal (insulin and glucagon) artificial pancreas	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Integration of Continuous Glucose Monitoring Into a Bi-Hormonal Closed-Loop Artificial Pancreas for Automated Management of Type 1 Diabetes
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Device: 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
Experimental: Bi-hormonal without meal-priming bolus The insulin controller was entirely reactive to CGMG; there were no meal priming boluses and no meal announcements	Device: 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

Outcome Measures

Primary Outcome Measures

1. Mean Plasma Blood Glucose Achieved by the Bionic Pancreas (mg/dl) [48 hours]

Secondary Outcome Measures

1. Percentage of Time Spent With Blood Glucose < 60 mg/dl [48 hours]

2. Percentage of Time Spent With Blood Glucose <70 mg/dl [48 hours]

3. Percentage of Time Spent With Blood Glucose 70-180 mg/dl [48 hours]

4. Insulin Total Daily Dose [48 hours]

5. Number of Carbohydrate Interventions for Hypoglycemia [48 hours]

6. Number of Blood Glucose Events < 70 mg/dl [48 hours]

7. Nadir Blood Glucose in Each Arm [48 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Boston University Charles River Campus
• Massachusetts General Hospital
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Juvenile Diabetes Research Foundation
• The Leona M. and Harry B. Helmsley Charitable Trust

Investigators

• Principal Investigator: Steven J Russell, MD, PhD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Edward R. Damiano, Associate Professor of Biomedical Engineering, Boston University
• ClinicalTrials.gov Identifier: NCT01161862
• Other Study ID Numbers: H-29293; 1R01DK085633-01
• First Posted: Jul 14, 2010
• Last Update Posted: Nov 14, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Edward R. Damiano, Associate Professor of Biomedical Engineering, Boston University: Closed-loop; Artificial pancreas; Bi-hormonal; Insulin; Glucagon; Diabetes mellitus type 1
• Additional relevant MeSH terms: Diabetes Mellitus; Glucagon; Pancrelipase

Study Results

Participant Flow

Recruitment Details	Twelve adult and twelve pediatric subjects with type 1 diabetes and no endogenous insulin secretion participated in two 51-h experiments. The protocol was approved by the Massachusetts General Hospital (MGH) and Boston University Human Research Committees

Arm/Group Title	Bi-hormonal Bionic Pancreas With Meal-priming Bolus	Bi-hormonal Bionic Pancreas With no Meal-priming Bolus
Arm/Group Description	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.	Bi-hormonal bionic pancreas with no meal-priming bolus. The controller was entirely reactive to CGMG; there were no meal priming boluses and no meal announcements
Period Title: Overall Study
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Bi-hormonal Pancreas With Meal-priming Bolus	Bi-hormonal Pancreas Without Meal-priming Bolus	Total
Arm/Group Description	An automatically adapting meal priming bolus was given by the controller at the time each meal was presented	The insulin controller was entirely reactive to CGMG; there were no meal priming boluses and no meal announcements	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	6 50%	6 50%	12 50%
Between 18 and 65 years	6 50%	5 41.7%	11 45.8%
>=65 years	0 0%	1 8.3%	1 4.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30 (17.7)	30.5 (19.0)	30 (18)
Sex: Female, Male (Count of Participants)
Female	7 58.3%	8 66.7%	15 62.5%
Male	5 41.7%	4 33.3%	9 37.5%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Mean Plasma Blood Glucose Achieved by the Bionic Pancreas (mg/dl)
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

Overall number of participants was 24, 12 in each arm

Arm/Group Title	Bionic Pancreas With Automated Meal-priming Bolus	Bionic Pancreas Without Automated Meal-priming Bolus
Arm/Group Description	Bi-hormonal bionic pancreas Bi-hormonal (insulin and glucagon) artificial pancreas
Measure Participants	12	12
Adults	132 (3)	146 (9)
Adolescents	162 (6)	175 (9)

2. Secondary Outcome

Title	Percentage of Time Spent With Blood Glucose < 60 mg/dl
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

Overall number of participants=24 (12 in each arm)

Arm/Group Title	Bionic Pancreas With Automated Meal-priming Bolus	Bionic Pancreas Without Automated Meal-priming Bolus
Arm/Group Description	Bi-hormonal bionic pancreas Bi-hormonal (insulin and glucagon) artificial pancreas
Measure Participants	12	12
Adults	2.3 (3.9)	1.4 (2.7)
Adolescents	0.1 (0.2)	0.1 (0.2)

3. Secondary Outcome

Title	Percentage of Time Spent With Blood Glucose <70 mg/dl
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

Overall number of participants=24 (12 in each arm)

Arm/Group Title	Bionic Pancreas With Automated Meal-priming Bolus	Bionic Pancreas Without Automated Meal-priming Bolus
Arm/Group Description	Bi-hormonal bionic pancreas Bi-hormonal (insulin and glucagon) artificial pancreas
Measure Participants	12	12
Adults	5.1 (6.7)	3.6 (4.5)
Adolescents	0.3 (0.5)	0.4 (0.7)

4. Secondary Outcome

Title	Percentage of Time Spent With Blood Glucose 70-180 mg/dl
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

Overall number of participants=24 (12 in each arm)

Arm/Group Title	Bionic Pancreas With Automated Meal-priming Bolus	Bionic Pancreas Without Automated Meal-priming Bolus
Arm/Group Description	Bi-hormonal bionic pancreas Bi-hormonal (insulin and glucagon) artificial pancreas
Measure Participants	12	12
Adults	80 (6)	70 (9)
Adolescents	68 (8)	60 (4)

5. Secondary Outcome

Title	Insulin Total Daily Dose
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

Overall number of participants=24 (12 in each arm)

Arm/Group Title	Bionic Pancreas With Automated Meal-priming Bolus	Bionic Pancreas Without Automated Meal-priming Bolus
Arm/Group Description	Bi-hormonal bionic pancreas Bi-hormonal (insulin and glucagon) artificial pancreas
Measure Participants	12	12
Adults	0.6 (0.2)	0.7 (0.2)
Adolescents	1.1 (0.2)	1.2 (0.2)

6. Secondary Outcome

Title	Number of Carbohydrate Interventions for Hypoglycemia
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

Overall number of participants=24 (12 in each arm)

Arm/Group Title	Bi-hormonal With Meal Priming Bolus	Bi-hormonal Without Meal Priming Bolus
Arm/Group Description	Bi-hormonal bionic pancreas Bi-hormonal (insulin and glucagon) artificial pancreas
Measure Participants	12	12
Number [Carbohydrate Interventions]	12	10

7. Secondary Outcome

Title	Number of Blood Glucose Events < 70 mg/dl
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bi-hormonal With Meal Priming Bolus	Bi-hormonal Without Meal Priming Bolus
Arm/Group Description	Bi-hormonal bionic pancreas Bi-hormonal (insulin and glucagon) artificial pancreas
Measure Participants	12	12
Number [Number of events]	59	48

8. Secondary Outcome

Title	Nadir Blood Glucose in Each Arm
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bionic Pancreas With Automated Meal-priming Bolus	Bionic Pancreas Without Automated Meal-priming Bolus
Arm/Group Description	Bi-hormonal bionic pancreas Bi-hormonal (insulin and glucagon) artificial pancreas	Bi-hormonal bionic pancreas Bi-hormonal (insulin and glucagon) artificial pancreas
Measure Participants	12	12
Mean (Standard Deviation) [mg/dl]	65.9 (17.4)	66.4 (17.8)

Adverse Events

Time Frame	51 hours per experiment
Arm/Group Title	Bi-hormonal With Meal Priming Bolus		Bi-hormonal Without Meal Priming Bolus
Arm/Group Description	Bi-hormonal with adaptive meal priming bolus		Bi-hormonal with no meal announcements or meal priming boluses
All Cause Mortality
	Bi-hormonal With Meal Priming Bolus		Bi-hormonal Without Meal Priming Bolus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Bi-hormonal With Meal Priming Bolus		Bi-hormonal Without Meal Priming Bolus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Bi-hormonal With Meal Priming Bolus		Bi-hormonal Without Meal Priming Bolus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		1/12 (8.3%)
General disorders
Nausea	1/12 (8.3%)	1	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.