Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials

NCT ID: NCT00105352

Last Updated: 2016-06-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-11-30

Study Completion Date

2005-11-30

Brief Summary

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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

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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.

Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Interventions

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Mixed Meal Tolerance Test

Intervention Type PROCEDURE

Glucagon Stimulation Test

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

8 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role collaborator

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

NIH

Sponsor Role lead

Principal Investigators

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Jay S Skyler, M.D.

Role: STUDY_CHAIR

University of Miami

Locations

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Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Barbara Davis Center for Childhood Diabetes, University of Colorado

Denver, Colorado, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

University of Miami School of Medicine

Miami, Florida, United States

Site Status

Riley Hospital for Children, Indiana University

Indianapolis, Indiana, United States

Site Status

Joslin Diabetes Center/ Children's Hospital Boston

Boston, Massachusetts, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Naomi Berrie Diabetes Center, Columbia University

New York, New York, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

University of Texas Medical Center at Dallas

Dallas, Texas, United States

Site Status

Benaroya Research Institute

Seattle, Washington, United States

Site Status

Walter and Eliza Hall Institute of Medical Research

Parkville, Victoria, Australia

Site Status

University of Toronto

Toronto, Ontario, Canada

Site Status

University of Turku

Turku, , Finland

Site Status

Vita-Salute San Raffaele University

Milan, , Italy

Site Status

University of Bristol

Bristol, , United Kingdom

Site Status

Countries

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United States Australia Canada Finland Italy United Kingdom

References

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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. doi: 10.2337/diabetes.53.1.250.

Reference Type BACKGROUND
PMID: 14693724 (View on PubMed)

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. doi: 10.2337/diabetes.52.5.1059. No abstract available.

Reference Type BACKGROUND
PMID: 12716733 (View on PubMed)

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. doi: 10.2337/dc07-2451. Epub 2008 Jul 15.

Reference Type DERIVED
PMID: 18628574 (View on PubMed)

Related Links

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http://diabetestrialnet.org

TrialNet Study Group

http://www.diabetes.org

American Diabetes Association

http://jdrf.org

Juvenile Diabetes Research Foundation, International

Other Identifiers

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MMTTGST (IND) (completed)

Identifier Type: -

Identifier Source: org_study_id

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