Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials

Overview:

The study is a multi-center, two-arm, randomized clinical trial. Each participant will
undergo four tests within a limited period according to the test sequence assignment. The
tests will randomly start with either MMTT or GST.

Specific Aims

- To compare the reliability of the MMTT and Glucagon stimulated C-peptide responses as
measured by time to peak C-peptide on MMTT, and the peak and AUC values on both tests.

- To determine the relationship between MMTT and Glucagon stimulated C-peptide responses
as measured by time to peak C-peptide on MMTT and peak and AUC values on both tests.

- To determine the impact of basal glucose, peak glucose, age of participant, time from
diagnosis, and basal C-peptide with respect to the reliability of measures and
relationship between MMTT and Glucagon results.

- Describe the palatability of, patient compliance with, and adverse effects of each test
(MMTT vs. GST) and to compare the participant and investigator burden to conduct the
MMTT and Glucagon tests.

TEST INFORMATION:

- Mixed Meal Tolerance Test (MMTT):

BOOST is a liquid meal (like a milkshake) containing a standard amount of fat, protein, and
carbohydrate. BOOST raises blood sugar and causes the pancreas to produce insulin. After
drinking BOOST, about one-half teaspoon of blood will be drawn through an IV line in the arm
after 15, 30, 60, 90, and 120 minutes. (Using an IV line avoids multiple needle sticks). The
test takes about 2 hours.

- Glucagon Stimulation Test (GST):

Glucagon is a hormone that circulates in the blood and stimulates insulin secretion.
Glucagon will be injected into the bloodstream through an IV line, and about one-half
teaspoon of blood will be drawn five times during ten minutes. The test takes about 30
minutes.

OTHER TEST INFORMATION:

- Participants will have tests on four different days over a six week period.
Participants will have either a) two MMTTs and then two GSTs OR b) two GSTs and then
two MMTTs. Each test will be done 3-10 days apart.

- Participants will follow a special high carbohydrate diet (150 grams) for at least
three days prior to each study visit. Dietary information will be provided.

- Participants will fast overnight (at least 8 hours) and arrive at the clinic between 7
AM - 10 AM.

- It is essential that participants have a blood glucose level of 70-200 mg/dl in the
morning before starting the test. If blood glucose is too high or too low the morning
of the test, the test will be re-scheduled on another day.

- Tests will be re-scheduled if, on the morning of the test, your blood sugar or ketones
are not within acceptable ranges. Testing could take up to eight visits if tests need
to be re-scheduled.

- Participants will learn whether their pancreas is still secreting insulin and, if so,
how much insulin is being secreted. This information may help their diabetes health
care team design for them a better insulin regimen and diabetes management program to
improve their longterm blood sugar control.

- This study will help researchers learn which test (MMTT or GST) is best to use in other
research studies looking at treatments that may stop or delay type 1 diabetes.

- Informed consent obtained from participants (over 12 years of age) and parents (for
participants below 18 years of age). Assent is obtained from younger children.

- Age 8 - 35 years at the time of inclusion

- Body weight > 30 kg

- Type 1 diabetes defined by: ADA (American Diabetes Association) criteria or judgment
of physician

- Duration of diabetes: 1 month to 3* years (*The TrialNet Coordinating Center will
monitor fasting C-peptide levels as they are reported to ensure that a wide range of
values is included. This review may result in widening the duration of diabetes
window to allow for subjects with low C-peptide).

- Must maintain good glycemic control

- Be willing to travel to a TrialNet Clinical Center for a minimum of four separate
visits that are spaced 3-10 days apart, and be willing to complete the study within a
six week period.

Exclusion Criteria:

- Actual treatment with drugs influencing beta cell function (e.g. oral hypoglycaemic
agents, beta-2-receptor agonists)

- Actual treatment with drugs influencing insulin sensitivity (e.g. steroids)

- Significant concomitant disease likely to interfere with glucose metabolism (e.g.
febrile illness within the prior 3 days)

- Expected poor compliance

- If a female of child-bearing age, currently pregnant or not using a form of birth
control

- Any other condition that by the judgement of the investigator may be potentially
harmful to the patients