Physiologic Response to Glucagon at Varying Insulin Levels

NCT01483651 | Completed Results DMC

• 1 other identifier: kw02
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to test how different levels of insulin block the effect of glucagon. Insulin is a hormone that lowers blood glucose. Glucagon raises blood glucose. Both are natural hormones made by people without diabetes. Sensor-based blood glucose control studies have been done by our research group using glucagon in small doses to prevent hypoglycemia (low blood sugar). However, sometimes glucagon does not work to raise blood sugar. The investigators believe this is because of too much insulin in the body. This study will help determine how different levels of insulin in the body affect the ability of glucagon to raise blood sugar.

Conditions

Type 1 Diabetes Mellitus

Keywords

diabetes; glucagon; insulin; dideuterated glucose

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve for Glucose Above Baseline

  The change in the rate of glucose appearance will be assessed by measuring the stable glucose isotope (dideuterated glucose, D2) using a gas chromatography-mass spectrometry assay. The units of the area under the curve are defined as milligrams per kilogram of glucose, since the dependent variable is a rate of glucose production \[mg/kg/min\] measured over time \[min\]. The time variable therefore cancels out. Additionally, this area under the curve is being normalized per microgram of glucagon delivered.

  60 minutes after each glucagon administration

Study Arms (6)

Low, Medium and High insulin infusion

EXPERIMENTAL

All study subjects in this arm were randomized as follows: First study is regular insulin infused at lowest level with glucagon administration. Second study is regular insulin infused at medium level with glucagon adminstration. Third study is regular insulin infused at highest level with glucagon administration.

Drug: Glucagon; Drug: Insulin

Low, High and Medium insulin infusion

EXPERIMENTAL

All study subjects in this arm were randomized as follows: First study is regular insulin infused at lowest level with glucagon administration. Second study is regular insulin infused at highest level with glucagon adminstration. Third study is regular insulin infused at medium level with glucagon administration.

Drug: Glucagon; Drug: Insulin

Medium, Low and High insulin infusion

EXPERIMENTAL

All study subjects in this arm were randomized as follows: First study is regular insulin infused at medium level with glucagon administration. Second study is regular insulin infused at lowest level with glucagon adminstration. Third study is regular insulin infused at highest level with glucagon administration.

Drug: Glucagon; Drug: Insulin

Medium, High and Low insulin infusion

EXPERIMENTAL

All study subjects in this arm were randomized as follows: First study is regular insulin infused at medium level with glucagon administration. Second study is regular insulin infused at highest level with glucagon adminstration. Third study is regular insulin infused at lowest level with glucagon administration.

Drug: Glucagon; Drug: Insulin

High, Low and Medium insulin infusion

EXPERIMENTAL

All study subjects in this arm were randomized as follows: First study is regular insulin infused at highest level with glucagon administration. Second study is regular insulin infused at lowest level with glucagon adminstration. Third study is regular insulin infused at medium level with glucagon administration.

Drug: Glucagon; Drug: Insulin

High, Medium and Low insulin infusion

EXPERIMENTAL

All study subjects in this arm were randomized as follows: First study is regular insulin infused at highest level with glucagon administration. Second study is regular insulin infused at medium level with glucagon adminstration. Third study is regular insulin infused at lowest level with glucagon administration.

Drug: Glucagon; Drug: Insulin

Interventions

Glucagon DRUG

The first dose of glucagon will be delivered approximately one hour after infusion of IV insulin has started. The subsequent three doses will be delivered every two hours. The dosage will depend on the IV insulin infusion (50 units regular insulin in 499.5 mL 0.9% saline): Study 1) insulin 0.01 units/kg/hour and glucagon doses (ug): 10,25,45,70; Study 2) insulin 0.02 units/kg/hr and glucagon doses (ug): 25,45,70,100; Study 3) insulin 0.04 units/kg/hr and glucagon doses (ug): 45,70,100,135; Study 4) insulin 0.08 units/kg/hr and glucagon doses (ug): 70,100,135,175. Insulin levels and glucagon doses will be randomized. Glucagon will be reconstituted with 10 mL of sterile water and administered subcutaneously.

Also known as: GlucaGen

High, Low and Medium insulin infusion; High, Medium and Low insulin infusion; Low, High and Medium insulin infusion; Low, Medium and High insulin infusion; Medium, High and Low insulin infusion; Medium, Low and High insulin infusion

Insulin DRUG

Insulin was administered at a low, medium or high infusion rate. The intervention sequence was randomly pre-determined for all participants.

Also known as: Regular insulin

High, Low and Medium insulin infusion; High, Medium and Low insulin infusion; Low, High and Medium insulin infusion; Low, Medium and High insulin infusion; Medium, High and Low insulin infusion; Medium, Low and High insulin infusion

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of type 1 diabetes mellitus for at least 1 year
• Male or female subjects 21 to 65 years of age
• Current use of an insulin pump
• Willingness to sign informed consent and HIPAA documents and follow all study procedures

You may not qualify if:

• Pregnancy or Lactation: For women of childbearing potential: there is a requirement for a negative urine pregnancy test and for agreement to use contraception during the study and for at least 1 month after participating in the study
• Renal insufficiency (serum creatinine of 2.0 mg/dL or greater)
• Liver abnormalities: Serum ALT or AST equal to or greater than 3 times the upper limit of normal; hepatic synthetic insufficiency as defined as a serum albumin of less than 3.3 g/dL; or serum bilirubin of over 2
• Adrenal insufficiency
• Hematocrit of less than or equal to 34%
• A history of cerebrovascular disease or coronary artery disease regardless of the time since occurrence
• Congestive heart failure, NYHA class III or IV
• Any active infection
• Active foot ulceration
• Severe peripheral arterial disease characterized by ischemic rest pain or severe claudication
• Active alcohol abuse, substance abuse, or severe mental illness (as judged by the principal investigator)
• Active malignancy, except basal cell or squamous cell skin cancers
• Major surgical operation within 30 days prior to screening
• Seizure disorder
• Any concurrent illness, other than diabetes, that is not controlled by a stable therapeutic regimen

Sponsors & Collaborators

• Legacy Health System: lead
• Juvenile Diabetes Research Foundation: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

Legacy Health System

Portland, Oregon, 97210, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Insulin Resistance

Interventions

Glucagon; Glucagon-Like Peptide 1; Insulin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Glucagon-Like Peptides; Gastrointestinal Hormones; Proinsulin; Insulins

Results Point of Contact

• Title: Kenneth Ward
• Organization: Legacy Health System

kenward503@msn.com

971-570-2632

Study Officials

• W Kenneth Ward, MD

  Legacy Health System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist

Study Record Dates

• First Submitted: November 29, 2011
• First Posted: December 1, 2011
• Study Start: November 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: March 29, 2016
• Results First Posted: September 22, 2014

Record last verified: 2016-03

Locations

US (1)