Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00105352




Registration number
NCT00105352
Ethics application status
Date submitted
11/03/2005
Date registered
14/03/2005
Date last updated
2/06/2016

Titles & IDs
Public title
Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials
Scientific title
Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials
Secondary ID [1] 0 0
MMTTGST (IND) (completed)
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 1 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Stimulated C-peptide response derived from the 2-hour MMTT and the glucagon stimulation test (GST)
Timepoint [1] 0 0
Primary outcome [2] 0 0
Time to peak C-peptide on MMTT, and the peak and AUC values from each test
Timepoint [2] 0 0
Primary outcome [3] 0 0
Co-efficient of reproducibility of the MMTT, and the GST, provided from the duplicate tests within the same individuals
Timepoint [3] 0 0

Eligibility
Key inclusion 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.
Minimum age
8 Years
Maximum age
35 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2005
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Walter and Eliza Hall Institute of Medical Research - Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Finland
State/province [12] 0 0
Turku
Country [13] 0 0
Italy
State/province [13] 0 0
Milan
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Bristol

Funding & Sponsors
Primary sponsor type
Government body
Name
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute of Allergy and Infectious Diseases (NIAID)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Juvenile Diabetes Research Foundation
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Government body
Name [4] 0 0
National Center for Research Resources (NCRR)
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT00105352
Trial related presentations / 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. doi: 10.2337/diabetes.53.1.250. 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. doi: 10.2337/diabetes.52.5.1059. No abstract available. Erratum In: Diabetes. 2003 Oct;52(10):2643.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Jay S Skyler, M.D.
Address 0 0
University of Miami
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00105352