Clinical trial NCT02966275: Post Bariatric Closed Loop Glucagon Trial
Official title: Closed-Loop Glucagon Administration For The Automated Treatment Of Post-Bariatric Hypoglycemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypoglycemia
Keywords: glucagon
continuous glucose monitorering (CGM)
artificial pancreas
hypoglycemia
post-bariatric hypoglycemia
bionic pancreas
bariatric surgery
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Joslin Diabetes Center
First posted: 2016-11-17
Enrollment: 10
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Area Over the Curve and <60 mg/dl (CGM) Measured in mg/dl *Min
timeFrame: 14 days
Secondary outcomes:
measure: Mean Continuous Glucose Monitor (CGM) Glucose
timeFrame: 2 weeks
measure: Percentage of Time With CGM Glucose Less Than 60 mg/dl Overnight (11:00 PM - 7:00 AM)
timeFrame: 14 days
measure: Percentage of Time With CGM Glucose Less Than 60 mg/dl During Daytime ( 7:00 AM-11:00 PM)
timeFrame: 14 days
measure: Percentage of Time Spent Within the Glucose Range 70-120 mg/dl
timeFrame: 14 days
measure: Percentage of Time Spent Within the Glucose Range 70-180 mg/dl
timeFrame: 14 days
measure: Percentage of Time Spent Within the Glucose Range >180 mg/dl
timeFrame: 14 days
measure: Fraction of Time Spent Within the Glucose Range >250 mg/dl
timeFrame: 2 weeks
measure: Mean Absolute Relative Deviation (MARD) of CGM vs. All StatStrip Xpress BG Measurements
timeFrame: 14 days
measure: Number of Carbohydrate Interventions for Hypoglycemia Per Day
timeFrame: 14 days
measure: Total Number of Grams of Carbohydrate Taken for Hypoglycemia Per Day
timeFrame: 14 days
measure: Total Glucagon Dosing (mcg/kg/24 Hours)
timeFrame: 2 weeks
measure: Number of Symptomatic Hypoglycemia Events Per Day
timeFrame: 14 days
measure: Percentage of Days When Participants Correctly Guessed Intervention (Glucagon vs Placebo) Out of a Total of 14 Days.
timeFrame: 2 weeks
measure: Number of Days With Nausea
timeFrame: 14 days
measure: Severity of Nausea on Daily E-mail Survey
timeFrame: 14 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital, Boston, Massachusetts
name: Steven J Russell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: