Diabetes Mellitus, Type 1NCT00105352
Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials
A study testing Mixed Meal Tolerance Test and Glucagon Stimulation Test in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 18 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 to 35 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Mixed Meal Tolerance Test and Glucagon Stimulation Test
- Type of treatment
- Surgery or procedure
- How many people
- 120 participants
- Where
- 18 sitesin 6 countries
- Study dates
- Nov 2004to Nov 2005
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
None listed.
Who cannot join
- 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
Trial locations and contacts
18 sites in 6 countries.
18 sites in 6 countries
United States13 sites
Joslin Diabetes Center/ Children's Hospital Boston
Boston, Massachusetts, 02215
University of Texas Medical Center at Dallas
Dallas, Texas, 75390-8858
Barbara Davis Center for Childhood Diabetes, University of Colorado
Denver, Colorado, 80262
University of Florida
Gainesville, Florida, 32610
Riley Hospital for Children, Indiana University
Indianapolis, Indiana, 46202
Children's Hospital Los Angeles
Los Angeles, California, 90027
University of Miami School of Medicine
Miami, Florida, 33101
University of Minnesota
Minneapolis, Minnesota, 58944
Naomi Berrie Diabetes Center, Columbia University
New York, New York, 10032
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15213
University of California San Francisco
San Francisco, California, 94143-0434
Benaroya Research Institute
Seattle, Washington, 358285
Stanford University Medical Center
Stanford, California, 94305-5208
Australia1 site
Walter and Eliza Hall Institute of Medical Research
Parkville, Victoria, 3050
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Mixed Meal Tolerance Test, Glucagon Stimulation Test
- Keywords
- Type 1 Diabetes Study Group, TrialNet, type 1 diabetes, juvenile onset diabetes
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mixed Meal Tolerance TestProcedure or surgery
Glucagon Stimulation TestProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2005 (estimated)
- Study startNov 2004
- Study completionNov 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 120 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- 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
- Jay S Skyler, M.D., Study chair, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00105352
- Sponsor's protocol ID
- MMTTGST (IND) (completed)
- Status last verified
- Jun 2016
- First submitted
- 11 Mar 2005
- Last updated
- 2 Jun 2016
- Results posted
- No
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.
PubMed 14693724Greenbaum 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.
PubMed 12716733Greenbaum 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.
PubMed 18628574
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Metabolic Assessments in Type 1 Diabetes Mellitus Clinical Trials
- ClinicalTrials.gov ID
- NCT00105352
- Acronym / sponsor ID
- MMTTGST (IND) (completed)
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Type 1 Diabetes Study Group, TrialNet, type 1 diabetes, juvenile onset diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- 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)
- Study start
- Nov 2004
- Study completion
- Nov 2005 (actual)
- First posted
- 14 Mar 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
Who may qualify
- Ages
- 8 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mixed Meal Tolerance Test | Procedure or surgery | – |
| Glucagon Stimulation Test | Procedure or surgery | – |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2016.
- Background: PubMed 14693724Palmer 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.
- Background: PubMed 12716733Greenbaum 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.
- Derived from this study: PubMed 18628574Greenbaum 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.
- TrialNet Study GroupLink provided by the sponsor.
- American Diabetes AssociationLink provided by the sponsor.
- Juvenile Diabetes Research Foundation, InternationalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jay S Skyler, M.D. study chair
University of Miami
18 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mixed Meal Tolerance Test and Glucagon Stimulation Test in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 18 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Australia, Canada, Finland, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stimulated C-peptide response derived from the 2-hour MMTT and the glucagon stimulation test (GST). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00105352, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2016.