Glucagon Counterregulation in Type 1 Diabetes

NCT03547427 | Terminated

• 1 other identifier: 20364
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes Mellitus

Keywords

Type 1 Diabetes Mellitus; Pramlintide; Lispro Insulin; Continuous Glucose Monitor (CGM); Acetaminophen; Hypoglycemia; Exercise

Outcome Measures

Primary Outcomes (1)

• Relative glucagon counterregulation (GCR) response

  The primary outcome is the relative glucagon counterregulation (GCR) response, computed as the ratio between average glucagon concentration in response to insulin-induced hypoglycemia, and the pre-hypoglycemic baseline value. The baseline glucagon level is defined as the average concentration of glucagon when the falling plasma glucose is below 100mg/dl but above the hypoglycemic threshold of 60mg/dl. The response to hypoglycemia is the average concentration of glucagon between the hypoglycemic threshold crossing point and the time of the meal ingestion.

  about 19 hours

Secondary Outcomes (2)

• Maximal glucagon counterregulation (GCR) response

  about 19 hours

• Rate of gastric emptying

  about 4 hours

Study Arms (4)

Insulin hypoglycemia + pramlintide

EXPERIMENTAL

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.

Other: Basal pramlintide and reduced basal insulin; Other: CGM; Other: Acetaminophen test; Other: Insulin-induced hypoglycemia

Insulin hypoglycemia

ACTIVE COMPARATOR

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.

Other: Basal insulin alone; Other: CGM; Other: Acetaminophen test; Other: Insulin-induced hypoglycemia

Exercise hypoglycemia + pramlintide

EXPERIMENTAL

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.

Other: Basal pramlintide and reduced basal insulin; Other: CGM; Other: Acetaminophen test; Other: Exercise-induced hypoglycemia

Exercise hypoglycemia

ACTIVE COMPARATOR

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.

Other: Basal insulin alone; Other: CGM; Other: Acetaminophen test; Other: Exercise-induced hypoglycemia

Interventions

Basal insulin alone 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.

Exercise hypoglycemia; Insulin hypoglycemia

Basal pramlintide and reduced basal insulin 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.

Exercise hypoglycemia + pramlintide; Insulin hypoglycemia + pramlintide

CGM 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.

Exercise hypoglycemia; Exercise hypoglycemia + pramlintide; Insulin hypoglycemia; Insulin hypoglycemia + pramlintide

Acetaminophen test OTHER

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

Exercise hypoglycemia; Exercise hypoglycemia + pramlintide; Insulin hypoglycemia; Insulin hypoglycemia + pramlintide

Insulin-induced hypoglycemia 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; Insulin hypoglycemia + pramlintide

Exercise-induced hypoglycemia 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; Exercise hypoglycemia + pramlintide

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia Center for Diabetes Technology

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Motor Activity

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Behavior

Study Officials

• Leon S. Farhy, PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 6, 2018
• Study Start: May 20, 2018
• Primary Completion: March 11, 2019
• Study Completion: March 11, 2019
• Last Updated: March 28, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: To be determined
• Access Criteria: To be determined

Locations

US (1)