T Cell Validation Study Using Blood Samples From Subjects With Recent Onset Type 1 Diabetes Mellitus

NCT ID: NCT00212329

Last Updated: 2016-05-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2007-09-30

Brief Summary

Type 1 diabetes is a condition that is caused in part by an abnormality of the immune system which occurs when T cells, which are part of the immune system, damage the insulin secreting cells (islet cells) in the pancreas. Although it is known that T cells are important mediators of the disease, progress in the development of reliable T cell assays has been modest. The purpose of this study is to learn which T cell assays are most reliable and reproducible so that the investigators can improve their understanding about how type 1 diabetes occurs.

Detailed Description

The T Cell Validation Study is designed to determine the ability of T cell assays to identify differences in responses from participants with type 1 diabetes compared to normal control subjects, and to compare four different laboratory tests which examine T cells to determine whether the measurements are quantitatively reproducible.

Antibody assays that confirm the presence of type 1 diabetes will be evaluated including: Diabetes Biochemical Autoantibody Assay (anti-GAD65, anti-ICA512, anti-insulin) and Islet Cell Autoantibody testing; genetic testing (deoxyribonucleic acid [DNA] and human leukocyte antigen [HLA]) will also be done to learn more about the T cell assays.

The following T Cell Assays will be conducted in individuals with type 1 diabetes, as well as those without type 1 diabetes:

• Cellular Immunoblot Testing
• T Cell Proliferation Assay
• Tetramer Assay
• Cytokine ELISpot Assay

Conditions

Type 1 Diabetes Mellitus

Study Design

• Study Time Perspective: PROSPECTIVE

Interventions

T Cell Proliferation and Autoreactivity Assays

Intervention Type: PROCEDURE

Cellular Immunoblot Assays

Intervention Type: PROCEDURE

Tetramer Studies

Intervention Type: PROCEDURE

Cytokine ELISPOT

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

To be eligible, individuals with type 1 diabetes must be:

• Diagnosed with type 1 diabetes within one year of first study visit
• 8-35 years of age at time of first visit
• Weigh > 40 kg (88 lbs) at time of first visit
• Individuals who will serve as control subjects who do not have type 1 diabetes cannot have a first degree or second degree relative with type 1 diabetes.

Exclusion Criteria

Individuals must not:

• Have any major illness
• Be taking any steroid medications
• If female, should not be pregnant or breastfeeding.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

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

NIH

Sponsor Role: lead

Principal Investigators

Jay E Skyler, MD

Role: STUDY_CHAIR

Type 1 Diabetes TrialNet Study Chairman

Locations

Childrens Hospital of Los Angeles

Los Angeles, California, United States

University of California, San Francisco

San Francisco, California, United States

Stanford University Medical Center

Stanford, California, United States

Barbara Davis Center for Childhood Diabetes

Denver, Colorado, United States

University of Florida

Gainesville, Florida, United States

University of Miami School of Medicine

Miami, Florida, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Joslin Diabetes Center

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Naomi Berrie Diabetes Center, Columbia University

New York, New York, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Benaroya Research Institute at Virginia Mason

Seattle, Washington, United States

University of Bristol

Bristol, , United Kingdom

Countries

United States; United Kingdom

References

Arif S, Tree TI, Astill TP, Tremble JM, Bishop AJ, Dayan CM, Roep BO, Peakman M. Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. J Clin Invest. 2004 Feb;113(3):451-63. doi: 10.1172/JCI19585.

Reference Type: BACKGROUND

PMID: 14755342 (View on PubMed)

Bensoussan D, Passa P, Canivet J, Levy-Toledano S, Caen J. [Letter: platelet aggregation and assay of Willebrand factor during diabetes mellitus]. Nouv Presse Med. 1975 Jan 18;4(3):195. No abstract available. French.

Reference Type: BACKGROUND

PMID: 1129082 (View on PubMed)

Miyazaki I, Cheung RK, Gaedigk R, Hui MF, Van der Meulen J, Rajotte RV, Dosch HM. T cell activation and anergy to islet cell antigen in type I diabetes. J Immunol. 1995 Feb 1;154(3):1461-9.

Reference Type: BACKGROUND

PMID: 7822811 (View on PubMed)

Nagata M, Kotani R, Moriyama H, Yokono K, Roep BO, Peakman M. Detection of autoreactive T cells in type 1 diabetes using coded autoantigens and an immunoglobulin-free cytokine ELISPOT assay: report from the fourth immunology of diabetes society T cell workshop. Ann N Y Acad Sci. 2004 Dec;1037:10-5. doi: 10.1196/annals.1337.002.

Reference Type: BACKGROUND

PMID: 15699487 (View on PubMed)

Peakman M, Tree TI, Endl J, van Endert P, Atkinson MA, Roep BO; Second International Immunology of Diabetes Society Workshop for Standardization ot T-cell Assays in Type 1 Diabetes. Characterization of preparations of GAD65, proinsulin, and the islet tyrosine phosphatase IA-2 for use in detection of autoreactive T-cells in type 1 diabetes: report of phase II of the Second International Immunology of Diabetes Society Workshop for Standardization of T-cell assays in type 1 diabetes. Diabetes. 2001 Aug;50(8):1749-54. doi: 10.2337/diabetes.50.8.1749.

Reference Type: BACKGROUND

PMID: 11473034 (View on PubMed)

Reijonen H, Mallone R, Heninger AK, Laughlin EM, Kochik SA, Falk B, Kwok WW, Greenbaum C, Nepom GT. GAD65-specific CD4+ T-cells with high antigen avidity are prevalent in peripheral blood of patients with type 1 diabetes. Diabetes. 2004 Aug;53(8):1987-94. doi: 10.2337/diabetes.53.8.1987.

Reference Type: BACKGROUND

PMID: 15277377 (View on PubMed)

Other Identifiers

Tcell (IND) (completed)

Identifier Type: -

Identifier Source: org_study_id