Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials

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Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials

This study has been completed.
Sponsors and Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Juvenile Diabetes Research Foundation
National Center for Research Resources (NCRR)

Information provided by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00105352

Purpose
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.

Condition Intervention
Diabetes Mellitus, Type 1
Procedure: Mixed Meal Tolerance Test
Procedure: Glucagon Stimulation Test

MedlinePlus related topics: Diabetes Diabetes Type 1
Drug Information available for: Glucagon
U.S. FDA Resources
Study Type:Interventional
Study Design:Diagnostic, Randomized, Open Label, Uncontrolled, Crossover Assignment, Safety/Efficacy Study
Official Title:Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
Stimulated C-peptide response derived from the 2-hour MMTT and the glucagon stimulation test (GST)

Time to peak C-peptide on MMTT, and the peak and AUC values from each test

Co-efficient of reproducibility of the MMTT, and the GST, provided from the duplicate tests within the same individuals

Estimated Enrollment:120
Study Start Date:November 2004
Study Completion Date:November 2005

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.
Eligibility
Ages Eligible for Study:8 Years to 35 Years
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No
Criteria
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
Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00105352

Locations
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Stanford University Medical Center
Stanford, California, United States, 94305-5208
University of California San Francisco
San Francisco, California, United States, 94143-0434
United States, Colorado
Barbara Davis Center for Childhood Diabetes, University of Colorado
Denver, Colorado, United States, 80262
United States, Florida
University of Florida
Gainesville,, Florida, United States, 32610
University of Miami School of Medicine
Miami, Florida, United States, 33101
United States, Indiana
Riley Hospital for Children, Indiana University
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Joslin Diabetes Center/ Children's Hospital Boston
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 58944
United States, New York
Naomi Berrie Diabetes Center, Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
University of Texas Medical Center at Dallas
Dallas, Texas, United States, 75390-8858
United States, Washington
Benaroya Research Institute
Seattle, Washington, United States, 358285
Australia, Victoria
Walter and Eliza Hall Institute of Medical Research
Parkville, Victoria, Australia, 3050
Canada, Ontario
University of Toronto
Toronto, Ontario, Canada, M5G-1X8
Finland
University of Turku
Turku, Finland, FIN-20520
Italy
Vita-Salute San Raffaele University
Milan, Italy, +39-02-2643 2818
United Kingdom
University of Bristol
Bristol, United Kingdom, BS10 5NB UK

Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Juvenile Diabetes Research Foundation
National Center for Research Resources (NCRR)
Investigators
Study Chair: Jay S Skyler, M.D. University of Miami

TrialNet Study Group
American Diabetes Association
Juvenile Diabetes Research Foundation, International

Publications:
Palmer JP, Fleming GA, Greenbaum CJ, Herold KC, Jansa LD, Kolb H, Lachin JM, Polonsky KS, Pozzilli P, Skyler JS, Steffes MW. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes. 2004 Jan;53(1):250-64. Erratum in: Diabetes. 2004 Jul;53(7):1934.
Greenbaum CJ, Harrison LC; Immunology of Diabetes Society. Guidelines for intervention trials in subjects with newly diagnosed type 1 diabetes. Diabetes. 2003 May;52(5):1059-65. No abstract available. Erratum in: Diabetes. 2003 Oct;52(10):2643.

Publications indexed to this study:
Greenbaum CJ, Mandrup-Poulsen T, McGee PF, Battelino T, Haastert B, Ludvigsson J, Pozzilli P, Lachin JM, Kolb H; Type 1 Diabetes Trial Net Research Group; European C-Peptide Trial Study Group. Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes. Diabetes Care. 2008 Oct;31(10):1966-71. Epub 2008 Jul 15.

Study ID Numbers:MMTTGST
First Received:March 11, 2005
Last Updated:November 15, 2007
ClinicalTrials.gov Identifier:NCT00105352 [history]
Health Authority:United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Type 1 Diabetes Study Group
TrialNet
type 1 diabetes
juvenile onset diabetes

Study placed in the following topic categories:
Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Glucagon
Diabetes Mellitus
Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders

Additional relevant MeSH terms:
Immune System Diseases