Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      OBJECTIVE:

      This study is being conducted by the Type 1 Diabetes TrialNet Study Group, funded by the
      National Institutes of Health, in collaboration with the European C-Peptide Group. The goal
      is to evaluate comparability and reproducibility of measures of beta cell function in type 1
      diabetes comparing the mixed meal tolerance tests (MMTT) and glucagon stimulation test (GST).
      These two tests will be compared to assess the relationship between the MMTT and IV
      (intravenous) Glucagon stimulated C-peptide responses as measured by time to peak C-peptide
      and AUC (area under the curve) values.

      Based on the understanding that type 1 diabetes results from an immune mediated loss of
      pancreatic beta cells, therapeutic trials and newer measures of beta cell function can be
      evaluated as endpoints for clinical trials. Direct assessment of residual beta cell function
      is an appropriate endpoint, as retention of beta cell function in patients with T1D is known
      to result in improved glycemic control and reduced hypoglycemia, retinopathy and nephropathy.
      Endogenous beta cell function or insulin secretion is best measured by determination of
      C-peptide (which is co-secreted with insulin in a 1:1 molar ratio). Intervention studies over
      the past few decades have usually used measurement of C-peptide. However, the relationship
      between these or other measures of beta cell function has not been well studied. The relative
      advantages of one measure over another in terms of variability, sensitivity and burden to the
      subject is unknown. In addition, the optimal conditions for the conduct of the test need to
      be determined.

      An important goal is to develop an international consensus about the conduct of metabolic
      tests in the context of large, multicenter trials involving type 1 diabetes (T1D) by
      balancing the scientific data with the burden on the subject.
    

Detailed description: 
      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.
    

Intervention name(s): Mixed Meal Tolerance Test; Glucagon Stimulation Test
Intervention type(s): Procedure; Procedure
Intervention MeSH terms: Glucagon
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Type 1 Diabetes Study Group; TrialNet; type 1 diabetes; juvenile onset diabetes