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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

A Comparative Study Between the Cytokine Elispot, Tetramer, Immunoblot, and T Cell Proliferation Assays Using Fresh Blood Samples From Subjects With Recent Onset Type 1 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00212329
• Other study ID #: Tcell (IND) (completed)
• Status: Completed
• Phase: N/A
• First received: September 13, 2005
• Last updated: May 12, 2016
• Start date: September 2005
• Est. completion date: September 2007

Study information

• Verified date: May 2016
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 8 Years to 35 Years

Eligibility

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.

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Procedure:
• T Cell Proliferation and Autoreactivity Assays

• Cellular Immunoblot Assays

• Tetramer Studies

• Cytokine ELISPOT

Locations

Country	Name	City	State
United Kingdom	University of Bristol	Bristol
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Barbara Davis Center for Childhood Diabetes	Denver	Colorado
United States	University of Florida	Gainesville	Florida
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Childrens Hospital of Los Angeles	Los Angeles	California
United States	University of Miami School of Medicine	Miami	Florida
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 California, San Francisco	San Francisco	California
United States	Benaroya Research Institute at Virginia Mason	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Countries where clinical trial is conducted

United States,  United Kingdom, 

References & Publications (6)

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. — View Citation

Bensoussan D, Passa P, Canivet J, Lévy-Toledano S, Caen J. [Letter: platelet aggregation and assay of Willebrand factor during diabetes mellitus]. Nouv Presse Med. 1975 Jan 18;4(3):195. French. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation