Clinical trial NCT03547427: Glucagon Counterregulation in Type 1 Diabetes
Official title: Enhancement of Glucagon Counterregulation in Type 1 Diabetes by Basal Amylin Replacement
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Keywords: Type 1 Diabetes Mellitus
Pramlintide
Lispro Insulin
Continuous Glucose Monitor (CGM)
Acetaminophen
Hypoglycemia
Exercise
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2018-06-06
Enrollment: 13
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The purpose of this study is to find out whether the combination of insulin and pramlintide is better than insulin alone at helping the pancreas release glucagon in response to a low blood sugar episode.

A secondary goal is to assess whether basal pramlintide will delay gastric emptying.

Detailed description: Participation in this study will require three (3) study visits over 12 weeks: one screening visit lasting 2-3 hours, and two overnight study visits at the university's Clinical Research Unit (CRU). The two overnight visits will last about 22 hours.

During the CRU admission, all subjects will wear a Continuous Glucose Monitor (CGM) starting 2-3 days prior to the CRU admission and after having a CGM training.

Eligible subjects will be randomized to either insulin- or exercise-induced hypoglycemia group. Each subject will have two overnight CRU admissions in randomized order: Experimental (basal pramlintide + 25% reduction of basal insulin) or Control (standard basal insulin therapy) admissions. During these two admissions, the study team will deliberately induce hypoglycemia as follows:

Subjects randomized to insulin-induced hypoglycemia admission will receive an insulin bolus(s) dosed to reach blood sugar of less than 55 mg/dL.

Subjects randomized to exercise-induced hypoglycemia will participate in three 15 minute exercise bouts (45 minutes total) to lower blood sugar to less than 55 mg/dL.

After hypoglycemia induction, all subjects will receive one and the same standard meal (lunch) mixed with 1.5 g liquid acetaminophen to measure how quickly acetaminophen is absorbed to estimate the rate of gastric emptying.

The study team will collect blood samples during the hypoglycemic induction and the gastric emptying monitoring which will be analysed for levels of various substances used to address the study goals.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least 5 years and using insulin for at least 5 years
* Use of an insulin pump for at least 6 months with established parameters for basal rate(s), carbohydrate ratio(s) and insulin sensitivity factor(s) for at least 3 months.
* HbA1c level \<10.5% at screening
* Demonstration of proper mental status and cognition for the study
* Investigator has confidence that the subject can successfully operate all study devices and is capable of adhering to the protocol

Exclusion Criteria:

* Admission for diabetic ketoacidosis in the 6 months prior to enrollment.
* Severe hypoglycemia resulting in seizure or loss of consciousness in the 3 months prior to enrollment.
* Hematocrit less that the lower limit of normal for the assay.
* Pregnancy, breast-feeding, or intention of becoming pregnant over time of study procedures
* A known medical condition, which in the opinion of the investigator or designee, would put the participant or study at risk
* A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the protocol
* Current use of some drugs and supplements
* Participation in another pharmaceutical or device trial at the time of enrollment or during the study
* Basal insulin rates less than 0.01 units per hour
* Diagnosed food allergies that would prohibit the consumption of a standardized meal
* Any reason the study MD considers that the subject is not appropriate for the trial

Primary outcomes:
measure: Relative glucagon counterregulation (GCR) response
timeFrame: about 19 hours
Secondary outcomes:
measure: Maximal glucagon counterregulation (GCR) response
timeFrame: about 19 hours
measure: Rate of gastric emptying
timeFrame: about 4 hours
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Center for Diabetes Technology
state: Virginia
Study officials:
affiliation: University of Virginia
name: Leon S. Farhy, PhD
role: PRINCIPAL_INVESTIGATOR
References: