T1DES: Type 1 Diabetes Extension Study
Study Details
Study Description
Brief Summary
This is a multi-center, prospective, non-interventional study that focuses on the long- term effects following participation in selected ITN new-onset Type1 Diabetes Mellitus studies with immunomodulatory agents (T1DM, T1D).
This observational study will:
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follow participants to determine how long they continue to produce insulin, and
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will also assess how changes in the immune system over time relate to the ability to produce insulin.
This information could help design better therapies for type 1 diabetes in the future.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Depending upon a participant's level of insulin production, participation may be as short as one return visit or a maximum of five years. Evaluation visits will include:
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Overall health assessments
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Blood and urine collections
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Mixed meal tolerance test (MMTTs) for certain participants, per protocol.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Group 1: Detectable C-peptide by MMTT Participants with detectable C-peptide at their: Last Immune Tolerance Network (ITN) T1DM week 104 study visit, Last AbATE (NCT00129259) follow-up visit, or Last ITN066AI T1DES visit Detectable C-peptide is defined as a value above the lower limit of detection. |
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| Group 2:Undetectable C-peptide by MMTT Participants without detectable C-peptide at their: Last ITN T1DM week 104 study visit, Last AbATE follow-up visit, or last ITN066AI T1DES visit Undetectable C-peptide is defined as a value below the lower limit of detection. |
Outcome Measures
Primary Outcome Measures
- Change in Beta Cell Function by MMTT-Stimulated Mean C-peptide Area Under the Curve (AUC) [Baseline (Visit 0) to Month 60 (Year 5)]
Evaluation of changes in beta cell function over time will be measured by mixed-meal tolerance test (MMTT) -Stimulated mean C-Peptide area under the curve (AUC). C-peptide is released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. Detectable C-peptide is defined as any value during a MMTT of ≥0.15 ng/mL.
Secondary Outcome Measures
- Change in Insulin Use in Units per Kilogram Body Weight Per Day [Baseline (Visit 0) to Month 60 (Year 5)]
The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity.
- Change in HbA1C [Baseline (Visit 0) to Month 60 (Year 5)]
Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease.
- Count of Participant-Reported Major Hypoglycemic Events [Baseline (Visit 0) to Month 60 (Year 5)]
Major hypoglycemic events are defined as a glucose concentration <55 mg/dL (grades 2-5, NCI-CTCAE version 4.03), or clinically: involving seizure(s) or involving loss of consciousness (coma), or requiring assistance from another individual in order to recover.
- Time to Undetectable C-Peptide [Baseline (Visit 0) to Month 60 (Year 5)]
To assess the longevity of beta cell function, time to undetectable C-peptide will be evaluated using Kaplan-Meier survival estimates.
- Frequency of Grade 3 or Higher Adverse Events (AEs) of Interest [Baseline (Visit 0) to Month 60 (Year 5)]
Events of interest include but are not limited to: Opportunistic and serious infections Malignancy Cardiovascular disease Development of autoimmune disease(s) Hypersensitivity reactions to unrelated allergens Reference for Grade 3 or higher AEs: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 (June 14, 2010).
- Severity of Grade 3 or Higher Adverse Events (AEs) of Interest [Baseline (Visit 0) to Month 60 (Year 5)]
Events of interest include but are not limited to: Opportunistic and serious infections Malignancy Cardiovascular disease Development of autoimmune disease(s) Hypersensitivity reactions to unrelated allergens Reference for Grade 3 or higher AEs: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 (June 14, 2010).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Prior participant in an Immune Tolerance Network (ITN) executive committee approved T1DM study.
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Ability to sign informed consent/assent (as applicable for children).
Exclusion Criteria:
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Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial; or
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Inability to comply with the study visit schedule and required assessments.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCSF School of Medicine | San Francisco | California | United States | 94143 |
| 2 | Stanford University | Stanford | California | United States | 94305 |
| 3 | University of Colorado School of Medicine: Barbara Davis Center for Diabetes | Aurora | Colorado | United States | 80045 |
| 4 | Yale University | New Haven | Connecticut | United States | 06519 |
| 5 | Emory University | Atlanta | Georgia | United States | 30322 |
| 6 | Indiana University Riley Hospital for Children | Indianapolis | Indiana | United States | 46202 |
| 7 | University of Iowa Health Care Division of Pediatric Endocrinology | Iowa City | Iowa | United States | 52242 |
| 8 | Joslin Diabetes Center | Boston | Massachusetts | United States | 02215 |
| 9 | University of Minnesota | Minneapolis | Minnesota | United States | 55454 |
| 10 | Children's Mercy Hospital | Kansas City | Missouri | United States | 64108 |
| 11 | Sanford Research | Sioux Falls | South Dakota | United States | 57104 |
| 12 | Benaroya Research Institute | Seattle | Washington | United States | 98101 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Immune Tolerance Network (ITN)
Investigators
- Study Chair: Linda A. DiMeglio, MD, MPH,MA, Riley Hospital for Children at Indiana University Health
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- National Institute of Allergy and Infectious Diseases (NIAID)
- Division of Allergy, Immunology, and Transplantation (DAIT)
- ITN T1D Extended Study (T1DES) website
Publications
- Herold KC, Gitelman SE, Ehlers MR, Gottlieb PA, Greenbaum CJ, Hagopian W, Boyle KD, Keyes-Elstein L, Aggarwal S, Phippard D, Sayre PH, McNamara J, Bluestone JA; AbATE Study Team. Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes. 2013 Nov;62(11):3766-74. doi: 10.2337/db13-0345. Epub 2013 Jul 8.
- Rigby MR, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Patel CM, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Moran A, Russell WE, Pinckney A, Keyes-Elstein L, Howell M, Aggarwal S, Lim N, Phippard D, Nepom GT, McNamara J, Ehlers MR; T1DAL Study Team. Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Diabetes Endocrinol. 2013 Dec;1(4):284-94. doi: 10.1016/S2213-8587(13)70111-6. Epub 2013 Sep 23.
- Rigby MR, Harris KM, Pinckney A, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Keyes-Elstein L, Long SA, Kanaparthi S, Lim N, Phippard D, Soppe CL, Fitzgibbon ML, McNamara J, Nepom GT, Ehlers MR. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients. J Clin Invest. 2015 Aug 3;125(8):3285-96. doi: 10.1172/JCI81722. Epub 2015 Jul 20.
- DAIT ITN066AI
- NIAID CRMS ID#: 20722