Abstract

The Berrie Center is uniquely situated to contribute to the design and conduct of T1DM trials as part of TrialNet. The Berrie Center combines multi-disciplinary clinical care for patients with diabetes and clinical and basic research programs in diabetes all in one facility. The close geographic proximity of clinicians, scientists, patients, and clinical research subjects facilitates excellent and seamless collaboration and cross-fertilization and provides a unique and vibrant research environment that fosters translational research. The Berrie Center is the only multi- disciplinary diabetes center in New York City, with a large and growing referral base and a staff and patient population interested in type 1 diabetes research. The Berrie Center has been a very productive and contributing member of the TrialNet group. Although we've been a Major Affiliate rather than a Clinical Center for the past several years, our level of participation in the intervention trials has been at the level of a Clinical Center, randomizing 6-7% of total subjects into the treatment and prevention trials. In addition, we have supervised a productive Affiliate Network of 12 TrialNet affiliate sites. Therapeutic targeting of the SYK protein tyrosine kinase is a promising area of clinical investigation. Pre-clinical studies have established that an orally available small molecule syk inhibitor, R788, can prevent collagen-induced arthritis and prevent/treat NZB/NZW lupus nephritis. Phase II clinical studies in rheumatoid arthritis and ITP have demonstrated encouraging efficacy and manageable toxicities and continued evaluation in these diseases as well as in SLE are on-going. We have demonstrated the ability of R788 to inhibit cross-presentation and T1DM development in NOD mice, providing proof-of principal for this approach in T1DM. As a key component of this TrialNet application, we propose an intervention study to investigate its efficacy in human subjects with new-onset T1DM (onset within 100 days of randomization).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK085504-05
Application #
8468695
Study Section
Special Emphasis Panel (ZDK1-GRB-R (O1))
Program Officer
Leschek, Ellen W
Project Start
2009-09-30
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2013
Total Cost
$234,808
Indirect Cost
$96,620

  Institution

Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Redondo, Maria J; Steck, Andrea K; Sosenko, Jay et al. (2018) Transcription Factor 7-Like 2 (TCF7L2) Gene Polymorphism and Progression From Single to Multiple Autoantibody Positivity in Individuals at Risk for Type 1 Diabetes. Diabetes Care 41:2480-2486
Sanda, Srinath; Type 1 Diabetes TrialNet Study Group (2018) Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests. Pediatr Diabetes 19:271-276
Redondo, Maria J; Geyer, Susan; Steck, Andrea K et al. (2018) A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk. Diabetes Care 41:1887-1894
Redondo, Maria J; Geyer, Susan; Steck, Andrea K et al. (2018) TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes. Diabetes Care 41:311-317
Sosenko, Jay M; Geyer, Susan; Skyler, Jay S et al. (2018) The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1. Pediatr Diabetes 19:403-409
Ismail, Heba M; Xu, Ping; Libman, Ingrid M et al. (2018) The shape of the glucose concentration curve during an oral glucose tolerance test predicts risk for type 1 diabetes. Diabetologia 61:84-92
Culina, Slobodan; Lalanne, Ana Ines; Afonso, Georgia et al. (2018) Islet-reactive CD8+ T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. Sci Immunol 3:
Vecchio, Federica; Lo Buono, Nicola; Stabilini, Angela et al. (2018) Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes. JCI Insight 3:
Writing Committee for the Type 1 Diabetes TrialNet Oral Insulin Study Group; Krischer, Jeffrey P; Schatz, Desmond A et al. (2017) Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes: A Randomized Clinical Trial. JAMA 318:1891-1902
Bosi, Emanuele; Boulware, David C; Becker, Dorothy J et al. (2017) Impact of Age and Antibody Type on Progression From Single to Multiple Autoantibodies in Type 1 Diabetes Relatives. J Clin Endocrinol Metab 102:2881-2886

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