Clinical trial NCT00212329: T Cell Validation Study Using Blood Samples From Subjects With Recent Onset Type 1 Diabetes Mellitus
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 1 Diabetes Mellitus
Keywords: Type 1 Diabetes
Juvenile Onset Diabetes
Insulin Dependent Diabetes
T1D
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
First posted: 2005-09-21
Enrollment: 100
Sex: ALL
Minimum age (years): 8
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Time perspective: PROSPECTIVE

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

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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital of Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: Barbara Davis Center for Childhood Diabetes
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Naomi Berrie Diabetes Center, Columbia University
state: New York
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason
state: Washington
city: Bristol
country: United Kingdom
facility: University of Bristol
Study officials:
affiliation: Type 1 Diabetes TrialNet Study Chairman
name: Jay E Skyler, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
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.
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. doi: 10.1196/annals.1337.002.
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. doi: 10.2337/diabetes.50.8.1749.
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. doi: 10.2337/diabetes.53.8.1987.