Sensor-Augmented Insulin Delivery: Insulin Plus Glucagon Versus Insulin Alone

NCT00797823 | Completed Phase 2 Results

• 1 other identifier: IRB4311
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to test an insulin and glucagon delivery algorithm designed to be used in conjunction with a continuous glucose monitoring system. This combined glucose sensing/hormone delivery approach is a step on the way to eventual development of an artificial (or automated) pancreas. The insulin and glucagon delivery algorithm is based on the difference between the current blood glucose and the target glucose (proportional error) and the rate of change in blood glucose (derivative error), both adjusted for the recent glucose history. This algorithm is called the Fading Memory Proportional-Derivative (FMPD) Algorithm. The principal investigator of this study has published previous research regarding the use of this algorithm and found it to be well-suited to control blood glucose in type 1 diabetic animals. The addition of glucagon was helpful; better glycemic control with fewer glucose excursions were observed when small intermittent infusions of subcutaneous glucagon were given during times of impending low blood sugar (Ward et al. 2008).

Conditions

Type 1 Diabetes

Keywords

diabetes; pancreas; beta cell; glucagon; insulin; hypoglycemia

Outcome Measures

Primary Outcomes (1)

• Effectiveness of Closed Loop Diabetes Control

  Effectiveness of closed loop diabetes control will be measured by mean glucose.

  1 year

Secondary Outcomes (1)

• Percent of Time Venous Blood Glucose <70 mg/dl

  1 year

Study Arms (3)

Insulin + Placebo

PLACEBO COMPARATOR

Glycemic control of subject participants was managed by the closed-loop system which delivered insulin and normal saline (instead of glucagon) as a placebo, based upon algorithm calculations.

Drug: Insulin, Asp(B28)-; Drug: Placebo

Insulin + Glucagon

ACTIVE COMPARATOR

Glycemic control of subject participants was managed by the system which delivered insulin and glucagon based upon algorithm calculations.

Drug: Insulin, Asp(B28)-; Drug: Glucagon

Pilot Study

EXPERIMENTAL

Pilot studies designed to assess safety of the system. Includes 6 participants undergoing 7 studies.

Drug: Insulin, Asp(B28)-; Drug: Glucagon; Drug: Placebo

Interventions

Insulin, Asp(B28)- DRUG

Insulin dosing and frequency calculated by Fading Memory Proportional Derivative algorithm

Also known as: Aspart insulin, Novolog

Insulin + Glucagon; Insulin + Placebo; Pilot Study

Glucagon DRUG

During incipient hypoglycemia, glucagon was given in an attempt to prevent overt hypoglycemia. Dosing and frequency was calculated by the Fading Memory Proportional Derivative algorithm

Also known as: Glucagen

Insulin + Glucagon; Pilot Study

Placebo DRUG

Saline solution 0.9%

Also known as: Normal saline, NaCl 0.9%

Insulin + Placebo; Pilot Study

Eligibility Criteria

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

You may qualify if:

• Age 21-65, history of Type 1 Diabetes Mellitus for \> 3 months.
• Women:
• For women of childbearing potential, a negative urine pregnancy test is required on the first day of the study prior to sensor insertion AND the subject must agree to use contraception prior to and during the study.
• For menopausal women or those who have undergone surgical sterilization, no pregnancy test or contraception will be required.
• Willingness to attend all clinic visits and participate in two 28-hour studies or one 9-hour study.
• Hemoglobin A1C of 5.0-10%. (Values below 5.0 suggest a severe tendency towards hypoglycemia, and values above 10% suggest severely uncontrolled diabetes with risk for ketoacidosis.)
• Body mass index of 19-35.

You may not qualify if:

• Pregnancy, lactation or refusal to use contraception.
• Use of any investigational drug during the 30 days prior to screening.
• Enrollment or participation in any other research studies 30 days prior to and during the entirety of sensor insertion.
• Current alcohol abuse, substance abuse, or severe mental illness (as judged by the Principal Investigator (PI)).
• Any prior cerebrovascular accident or major permanent neurological damage such as aphasia, hemiparesis, or dementia.
• A history of cerebrovascular disease or cardiovascular disease regardless of the time since occurrence.
• Coronary artery disease (symptomatic or asymptomatic) as manifested by unstable angina, acute coronary syndrome, myocardial infarction or therapeutic coronary procedure (e.g., Percutaneous Transluminal Coronary Angioplasty (PTCA), stent placement, Coronary Artery By-pass Grafting (CABG)) within the prior 6 months.
• Any degree of heart failure (as defined by New York Heart Association)..
• Renal insufficiency (serum creatinine of \> 2.5).
• Current foot or leg ulceration.
• Peripheral arterial disease with uncontrolled claudication.
• Active uncontrolled malignancy except basal cell or squamous cell skin cancers.
• Concurrent illness, other than diabetic mellitus, that is not controlled by a stable therapeutic regimen.
• Hemoglobin A1C of less than 5.0 or greater than 10%.
• A total bilirubin level above 1.5 mg/dl.

Sponsors & Collaborators

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

Study Sites (1)

Legacy Research

Portland, Oregon, 97232, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Insulin Resistance; Hypoglycemia

Interventions

Insulin Aspart; Glucagon; Glucagon-Like Peptide 1; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Proglucagon; Glucagon-Like Peptides; Gastrointestinal Hormones; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: W Kenneth Ward MD
• Organization: Legacy Health System

wardk@ohsu.edu

503-413-5171

Study Officials

• William K. Ward, MD

  Legacy Health System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist

Study Record Dates

• First Submitted: November 24, 2008
• First Posted: November 25, 2008
• Study Start: November 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: October 7, 2011
• Results First Posted: September 26, 2011

Record last verified: 2009-08

Locations

US (1)