Glucagon Counterregulation in Type 1 Diabetes

NCT ID: NCT03547427

Last Updated: 2022-03-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-20
• Study Completion Date: 2019-03-11

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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Insulin hypoglycemia + pramlintide

Subjects will have a 25% reduction in their standard basal insulin therapy with concurrent basal pramlintide infusion ('Basal pramlintide and reduced basal insulin'). They will receive a Lispro bolus to induce hypoglycemia of ≤55mg/dL ('Insulin-induced hypoglycemia'). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test.

Group Type: EXPERIMENTAL

Basal pramlintide and reduced basal insulin

Intervention Type: OTHER

A study insulin pump containing pramlintide will be programmed to deliver pramlintide at 6:1 pramlintide:insulin ratio. Simultaneously, a study insulin pump containing lispro insulin will be programmed to deliver basal lispro insulin at \~25% reduced rate from the subject's normal basal profile. The carbohydrate ratio(s) and insulin sensitivity factor(s) will be programmed per the subject's usual home parameters.

CGM

Intervention Type: OTHER

Subjects will be instructed to initiate a Continuous Glucose Monitor (CGM) session 2-3 days prior to both the experimental and control CRU admissions.

Acetaminophen test

Intervention Type: OTHER

Consumption of a standardized meal mixed with added 1.5 g liquid acetaminophen

Insulin-induced hypoglycemia

Intervention Type: OTHER

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

Insulin hypoglycemia

Subjects will have their standard basal insulin treatment ('Basal insulin alone') and receive a Lispro bolus to induce hypoglycemia of ≤55mg/dL ('Insulin-induced hypoglycemia'). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test.

Group Type: ACTIVE_COMPARATOR

Basal insulin alone

Intervention Type: OTHER

A study insulin pump containing lispro insulin will be programmed to deliver basal lispro insulin at according to the subject's normal basal profile. The carbohydrate ratio(s) and insulin sensitivity factor(s) will be programmed per the subject's usual home parameters.

CGM

Intervention Type: OTHER

Subjects will be instructed to initiate a Continuous Glucose Monitor (CGM) session 2-3 days prior to both the experimental and control CRU admissions.

Acetaminophen test

Intervention Type: OTHER

Consumption of a standardized meal mixed with added 1.5 g liquid acetaminophen

Insulin-induced hypoglycemia

Intervention Type: OTHER

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

Exercise hypoglycemia + pramlintide

Subjects will have a 25% reduction in their standard basal insulin therapy with concurrent basal pramlintide infusion ('Basal pramlintide and reduced basal insulin'). They will have three bouts of exercise to induce hypoglycemia of ≤55mg/dL ('Exercise-induced hypoglycemia'). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test.

Group Type: EXPERIMENTAL

Basal pramlintide and reduced basal insulin

Intervention Type: OTHER

A study insulin pump containing pramlintide will be programmed to deliver pramlintide at 6:1 pramlintide:insulin ratio. Simultaneously, a study insulin pump containing lispro insulin will be programmed to deliver basal lispro insulin at \~25% reduced rate from the subject's normal basal profile. The carbohydrate ratio(s) and insulin sensitivity factor(s) will be programmed per the subject's usual home parameters.

CGM

Intervention Type: OTHER

Subjects will be instructed to initiate a Continuous Glucose Monitor (CGM) session 2-3 days prior to both the experimental and control CRU admissions.

Acetaminophen test

Intervention Type: OTHER

Consumption of a standardized meal mixed with added 1.5 g liquid acetaminophen

Exercise-induced hypoglycemia

Intervention Type: OTHER

During exercise-induced hypoglycemia admission, subjects participate in three 15 minute exercise bouts (45 minutes total) to lower blood sugar to less than 55 mg/dL.

Exercise hypoglycemia

Subjects will have their standard basal insulin treatment ('Basal insulin alone'). They will have three bouts of exercise to induce hypoglycemia of ≤55mg/dL ('Exercise-induced hypoglycemia' ). After induction of hypoglycemia is completed subjects will have an acetaminophen test. Subjects will be instructed to initiate a CGM session 2-3 days prior to both the admissions. Blood samples will be collected during the hypoglycemic induction and acetaminophen test.

Group Type: ACTIVE_COMPARATOR

Basal insulin alone

Intervention Type: OTHER

A study insulin pump containing lispro insulin will be programmed to deliver basal lispro insulin at according to the subject's normal basal profile. The carbohydrate ratio(s) and insulin sensitivity factor(s) will be programmed per the subject's usual home parameters.

CGM

Intervention Type: OTHER

Subjects will be instructed to initiate a Continuous Glucose Monitor (CGM) session 2-3 days prior to both the experimental and control CRU admissions.

Acetaminophen test

Intervention Type: OTHER

Consumption of a standardized meal mixed with added 1.5 g liquid acetaminophen

Exercise-induced hypoglycemia

Intervention Type: OTHER

During exercise-induced hypoglycemia admission, subjects participate in three 15 minute exercise bouts (45 minutes total) to lower blood sugar to less than 55 mg/dL.

Interventions

Basal insulin alone

A study insulin pump containing lispro insulin will be programmed to deliver basal lispro insulin at according to the subject's normal basal profile. The carbohydrate ratio(s) and insulin sensitivity factor(s) will be programmed per the subject's usual home parameters.

Intervention Type: OTHER

Basal pramlintide and reduced basal insulin

A study insulin pump containing pramlintide will be programmed to deliver pramlintide at 6:1 pramlintide:insulin ratio. Simultaneously, a study insulin pump containing lispro insulin will be programmed to deliver basal lispro insulin at \~25% reduced rate from the subject's normal basal profile. The carbohydrate ratio(s) and insulin sensitivity factor(s) will be programmed per the subject's usual home parameters.

Intervention Type: OTHER

CGM

Subjects will be instructed to initiate a Continuous Glucose Monitor (CGM) session 2-3 days prior to both the experimental and control CRU admissions.

Intervention Type: OTHER

Acetaminophen test

Consumption of a standardized meal mixed with added 1.5 g liquid acetaminophen

Intervention Type: OTHER

Insulin-induced hypoglycemia

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

Intervention Type: OTHER

Exercise-induced hypoglycemia

During exercise-induced hypoglycemia admission, subjects participate in three 15 minute exercise bouts (45 minutes total) to lower blood sugar to less than 55 mg/dL.

Intervention Type: OTHER

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Leon Farhi, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Leon S. Farhy, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia Center for Diabetes Technology

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

20364

Identifier Type: -

Identifier Source: org_study_id