Post Bariatric Closed Loop Glucagon Trial | NCT02966275

NCT02966275

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Joslin Diabetes Center	OTHER

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Glucagon-only bionic pancreas - glucagon	Experimental	Subjects will wear the bionic pancreas that consists of a continuous glucose monitor linked to a smartphone running a hypoglycemia prevention algorithm that doses glucagon from an insulin pump through a subcutaneous infusion set. Subjects will continue to manage any hypoglycemia that occurs according to the current recommendations of their care provider.	Device: Glucagon-only bionic pancreas - glucagon
Glucagon-only bionic pancreas - placebo	Placebo Comparator	Subjects will wear the bionic pancreas that consists of a continuous glucose monitor linked to a smartphone running a hypoglycemia prevention algorithm that doses placebo from an insulin pump through a subcutaneous infusion set. Subjects will continue to manage any hypoglycemia that occurs according to the current recommendations of their care provider.	Device: Glucagon-only bionic pancreas - placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Glucagon-only bionic pancreas - glucagon	Device	A computer algorithm will automatically deliver glucagon based on the signal from a minimally invasive continuous glucose monitor.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Area Over the Curve and <60 mg/dl (CGM) Measured in mg/dl *Min	The measure for area over the curve is used when an integrated assessment (e.g., a measurement of something over a specific amount of time) is more useful in understanding a phenomenon. To calculate this measure, a method of approximation is often used. One way would be to estimate the curve via curve-fitting techniques. For this outcome, using area over the curve and <60mg/dl provides a more robust method of calculating amount of hypoglycemia (by including more severe degrees of hypoglycemia in the product of mg/dl*min as opposed to percentage of time below 60mg/dl.	14 days

Secondary Outcomes

Measure	Description	Time Frame
Mean Continuous Glucose Monitor (CGM) Glucose		2 weeks
Percentage of Time With CGM Glucose Less Than 60 mg/dl Overnight (11:00 PM - 7:00 AM)		14 days
Percentage of Time With CGM Glucose Less Than 60 mg/dl During Daytime ( 7:00 AM-11:00 PM)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age 21 years or older with a gastric bypass for more than 1 year.
Post-bariatric hypoglycemia with prior episodes of neuroglycopenia, unresponsive to dietary intervention (low glycemic index, controlled carbohydrate portions) and trial of acarbose therapy at the maximally tolerated dose. Other therapies will not exclude a subject as long as the therapy is continued during the study.
Otherwise healthy (mild chronic disease such as asthma, hypertension, and depression will be allowed if well controlled).
Self-reported frequency of documented hypoglycemia (BG < 60 mg/dl verified by capillary blood glucose measurements) of at least 2 times per week.

Exclusion Criteria:

Unable to provide informed consent.
Unable to comply with study procedures.
Current participation in another hypoglycemia related clinical trial other than one that is primarily observational in nature.
Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception.
Use of insulin and/or insulin secretogues as sulfonylurea, metglitides, and glitazones.
History of cystic fibrosis, pancreatitis, type 1 diabetes or other pancreatic disease.
End stage renal disease on dialysis (hemodialysis or peritoneal dialysis).
Any known liver or biliary disease including cirrhosis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, any form of viral hepatitis.
Congestive heart failure (established history of CHF, paroxysmal nocturnal dyspnea, or orthopnea).
Acute illness or exacerbation of chronic illness at the time of the study.
Known insulinoma or predominantly fasting pattern of hypoglycemia
Adrenal insufficiency. Congenital hyperinsulinemia presenting with hypoglycemia during infancy.
History of pheochromocytoma. Fractionated metanephrines will be tested in patients with history increasing the risk for a catecholamine secreting tumor:
Paroxysms of tachycardia, pallor, or headache.
Personal or family history of MEN 2A, MEN 2B, neurofibromatosis, or von Hippel-Lindau disease.
Episodic or treatment refractory (requiring 4 or more medications to achieve normotension) hypertension.
Untreated or inadequately treated mental illness (indicators would include symptoms such as psychosis, hallucinations, mania, and/or any psychiatric hospitalization in the last year).
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).
Unwilling or unable to refrain from drinking more than two drinks in an hour or more than four drinks in a day during the trial.
Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference.
History of adverse reaction to glucagon (including allergy) besides nausea and vomiting.
Unwilling or unable to completely avoid acetaminophen during the study period.
Any factors that, in the opinion of the principal investigator, would interfere with the safe completion of the study procedures.

Name	Affiliation	Role
Steven J Russell, MD, PhD	Massachusetts General Hospital, Boston, Massachusetts	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Massachusetts General Hospital		Boston	Massachusetts	02114	United States

Label	URL
Information about this and related studies	View source

ID	Title	Description
FG000	Glucagon-only Bionic Pancreas	Subjects will use the device every day and will fill the reservoir daily with glucagon or placebo (randomized, double blinded allocation for each day). Participants would be on glucagon or placebo for either 1 day or 2 days and then switch to the alternate arm. They could not be on the same arm for more than 2 days in a row. Glucagon-only Bionic Pancreas: A computer algorithm will automatically deliver glucagon based on the signal from a minimally invasive continuous glucose monitor.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Glucagon-only Bionic Pancreas	Subjects will use the device every day and will fill the reservoir daily with either glucagon or placebo (randomized, double blinded allocation for each day) for 14 days. Glucagon-only Bionic Pancreas: A computer algorithm will automatically deliver glucagon or placebo based on the signal from a minimally invasive continuous glucose monitor.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Area Over the Curve and <60 mg/dl (CGM) Measured in mg/dl *Min

The measure for area over the curve is used when an integrated assessment (e.g., a measurement of something over a specific amount of time) is more useful in understanding a phenomenon. To calculate this measure, a method of approximation is often used. One way would be to estimate the curve via curve-fitting techniques. For this outcome, using area over the curve and <60mg/dl provides a more robust method of calculating amount of hypoglycemia (by including more severe degrees of hypoglycemia in the product of mg/dl*min as opposed to percentage of time below 60mg/dl.

Posted

Mean

Standard Deviation

mg/dl *minute

14 days

ID	Title	Description
OG000	Glucagon-only Bionic Pancreas - Glucagon	Subjects will wear the bionic pancreas that consists of a continuous glucose monitor linked to a smartphone running a hypoglycemia prevention algorithm that doses glucagon from an insulin pump through a subcutaneous infusion set. Subjects will continue to manage any hypoglycemia that occurs according to the current recommendations of their care provider. Glucagon-only bionic pancreas - glucagon: A computer algorithm will automatically deliver glucagon based on the signal from a minimally invasive continuous glucose monitor.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Glucagon-only Bionic Pancreas - Glucagon	Subjects will wear the bionic pancreas that consists of a continuous glucose monitor linked to a smartphone running a hypoglycemia prevention algorithm that doses glucagon from an insulin pump through a subcutaneous infusion set. Subjects will continue to manage any hypoglycemia that occurs according to the current recommendations of their care provider. Glucagon-only bionic pancreas - glucagon: A computer algorithm will automatically deliver glucagon based on the signal from a minimally invasive continuous glucose monitor.

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases