Post Bariatric Closed Loop Glucagon Trial

Not Applicable

Completed

Conditions: Hypoglycemia

Interventions: Device: Glucagon-only bionic pancreas - placebo
Device: Glucagon-only bionic pancreas - glucagon

Registration Number: NCT02966275

Lead Sponsor: Massachusetts General Hospital

Brief Summary: This study is to test our automated hypoglycemia prevention and treatment device (glucagon-only bionic pancreas) in subjects that have undergone post-bariatric surgery that are experiencing symptoms of hypoglycemia.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Glucagon-only bionic pancreas - placebo	Glucagon-only bionic pancreas - placebo	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.
Glucagon-only bionic pancreas - glucagon	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.

Primary Outcome Measures

Name	Time	Method
Area Over the Curve and <60 mg/dl (CGM) Measured in mg/dl *Min	14 days	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Days When Participants Correctly Guessed Intervention (Glucagon vs Placebo) Out of a Total of 14 Days.	2 weeks
Percentage of Time Spent Within the Glucose Range 70-120 mg/dl	14 days
Percentage of Time Spent Within the Glucose Range 70-180 mg/dl	14 days
Percentage of Time Spent Within the Glucose Range >180 mg/dl	14 days
Number of Carbohydrate Interventions for Hypoglycemia Per Day	14 days	Number of carbohydrate interventions for hypoglycemia per day calculated from daily email survey
Percentage of Time With CGM Glucose Less Than 60 mg/dl During Daytime ( 7:00 AM-11:00 PM)	14 days
Percentage of Time With CGM Glucose Less Than 60 mg/dl Overnight (11:00 PM - 7:00 AM)	14 days
Total Number of Grams of Carbohydrate Taken for Hypoglycemia Per Day	14 days	Calculated from daily email survey
Number of Symptomatic Hypoglycemia Events Per Day	14 days	Number of symptomatic hypoglycemia events per day calculated from daily email survey
Number of Days With Nausea	14 days	Number of days with nausea calculated from daily survey
Severity of Nausea on Daily E-mail Survey	14 days	The visual analog scale (VAS) is a psychometric response scale which can be used in questionnaires. We used a simple VAS is a straight horizontal line of fixed length measuring 0-100mm with subscale markings every 10mm. The ends are defined as the extreme limits of the parameter to be measured (nausea) orientated from the left (least severity or 0) to the right (most severity or 100mm). Subjects can mark their response anywhere from 0 to 100mm. The mean severity of nausea for the group in each arm was calculated by averaging all responses in either arm.
Mean Continuous Glucose Monitor (CGM) Glucose	2 weeks
Fraction of Time Spent Within the Glucose Range >250 mg/dl	2 weeks
Mean Absolute Relative Deviation (MARD) of CGM vs. All StatStrip Xpress BG Measurements	14 days	MARD is computed using the difference between the CGM readings and the values measured at the same time by the reference measurement system. The mean (or average) of all the absolute relative deviations produces the MARD. In this study, the reference measurement system was the StatStrip Xpress meter, to which the CGM values were compared.
Total Glucagon Dosing (mcg/kg/24 Hours)	2 weeks