Effect of AC2993 With or Without Immunosuppression on Beta Cell Function in Patients With Type I Diabetes

Summary

This study will determine 1) the safety of AC2993 in patients with type I diabetes; 2) the ability of AC2993 to improve beta cell function; and 3) the effects of immunosuppression on beta cell function.

Type I diabetes is an autoimmune disease, in which the immune system attacks the beta cells of the pancreas. These cells produce insulin, which regulates blood sugar. AC2993 may improve the pancreas's ability to produce insulin and help control blood sugar, but it may also activate the original immune response that caused the diabetes. Thus, this study will examine the effects of AC2993 alone as well as in combination with immunosuppressive drugs.

Patients between 18 and 60 years of age who have type I diabetes mellitus may be eligible for this 20-month study. They must have had diabetes for at least 5 years and require insulin treatment. Candidates will be screened with a questionnaire, followed by medical history and physical examination, blood and urine tests, a chest x-ray and skin test for tuberculosis, electrocardiogram (EKG), and arginine stimulated C-peptide test (see description below). Participants will undergo the following tests and procedures:

Advanced screening phase: Participants undergo a diabetes education program, including instruction on frequent blood glucose monitoring, dietary education on counting carbohydrates, intensive insulin therapy, review of signs and symptoms of low blood sugar (hypoglycemia), and potential treatment with glucagon shots.

Patients must administer insulin via an insulin pump or take at least four injections per day including glargine (Lantus) insulin.

4-month run-in phase

* Arginine-stimulated C-peptide test: This test measures the body's insulin production. The patient is injected with a liquid containing arginine, a normal constituent of food that increases insulin release from beta cells into the blood stream. After the injection, seven blood samples are collected over 10 minutes.
* Mixed meal stimulated C-peptide test with acetaminophen: This test assesses the response of the beta cells to an ordinary meal and the time it takes for food to pass through the stomach. The patient drinks a food supplement and takes acetaminophen (Tylenol). Blood samples are then drawn through a catheter (plastic tube placed in a vein) every 30 minutes for 4 hours to measure levels of various hormones and the concentration of acetaminophen.
* Euglycemic clamp: This test measures the body's level of insulin resistance by measuring the amount of glucose necessary to compensate for an increased insulin level while maintaining a prespecified blood glucose level.

Conditions

• Diabetes Mellitus

Interventions

DRUG

AC2993 (exenatide)

Dose-escalation beginning with 2.5 μg administered subcutaneously twice per day (BID); then to 2.5 μg four times a day (QID); then to 5 μg four times a day; then to 10 μg four times a day.

DRUG

daclizumab (immunosuppressive)

2 mg/kg intravenously infused over 30 minutes every month for 12 months

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• AstraZeneca

  lead INDUSTRY

Principal Investigators

• Vice President, Research and Development, MD · Amylin Pharmaceuticals, LLC.

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2003-07-31

Primary Completion

2008-03-31

Completion

2008-03-31

Countries

• United States

Study Locations