? ? This is a five-year renewal application for the Thalassemia Clinical Research Network (TCRN). TCRN's mission is to accelerate research in the management of thalassemia. Syndromes encompassed by this mission include the ? thalassemias: homozygous or compound heterozygous plus Hemoglobin E/? thalassemia; and the alpha thalassemias: homozygous, hemoglobin H disease, and HbH/Constant Spring. The network is composed of four core U.S. sites, a data coordinating center, several large affiliated clinical sites in the U.S., Canada, and England, and several smaller regional """"""""satellite"""""""" sites to the core centers, in a cooperative agreement with NHLBI. Key strengths of the TCRN include a demonstrated ability of the investigators and sites cooperatively to standardize patient assessment and care; to design, implement and conduct clinical trials with observational, interventional, and ancillary designs. The multicenter network has been crucial due to sample size considerations. A pivotal accomplishment of the initial grant period is the establishment and analysis of the TCRN Registry, from which subjects for trials are identified. The registry now includes over 800 patients from 22 sites, including ?-thalassemia major (n=422), ? -thal intermedia (n=121), Hb E/ ? thal (n=103), transfusion-dependent a-thal major (n=9), HbH disease (n=l 05), and HbH/Constant Spring (n=44).
The Specific Aims of the renewal grant are: (I) To perform interventional clinical trials in key areas of thalassemia care. Two trials are proposed. First, a randomized, controlled trial to examine the effect of deferoxamine alone v. deferoxamine plus deferriprone, on cardiac disease due to transfusional iron overload. Second, a randomized trial of arginine v. placebo for pulmonary hypertension, an important problem in thalassemia intermedia and other hemolytic states. (II) To provide an infrastructure for development, launch, and prompt completion of small, innovative trials in thalassemia. (Ill) To improve assessment of phenotype and clinical outcomes in thalassemia, in order to facilitate current and future clinical trials. This will be accomplished by two studies. The Thalassemia Longitudinal Cohort study, as well as a detailed study of iron-related organ damage, comparing measures of iron burden in the heart, liver and pancreas, to outcomes of iron-related organ dysfunction. Combined with the proposed clinical trials and the ability to perform detailed genotype/phenotype correlations, these improved phenotype and outcome measures are powerful tools to enhance knowledge about thalassemia clinical care, as envisioned by the NIH's 2003 Director's Roadmap. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01HL065260-06
Application #
6964772
Study Section
Special Emphasis Panel (ZHL1-CSR-C (M2))
Program Officer
Moore, Robert Blaine
Project Start
2000-07-15
Project End
2010-06-30
Budget Start
2005-07-20
Budget End
2006-06-30
Support Year
6
Fiscal Year
2005
Total Cost
$217,529
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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Walter, Patrick B; Porter, John; Evans, Patricia et al. (2013) Increased leucocyte apoptosis in transfused ?-thalassaemia patients. Br J Haematol 160:399-403
Kwiatkowski, Janet L; Kim, Hae-Young; Thompson, Alexis A et al. (2012) Chelation use and iron burden in North American and British thalassemia patients: a report from the Thalassemia Longitudinal Cohort. Blood 119:2746-53
Fung, Ellen B; Xu, Yan; Trachtenberg, Felicia et al. (2012) Inadequate dietary intake in patients with thalassemia. J Acad Nutr Diet 112:980-90
Quinn, Charles T; Johnson, Valerie L; Kim, Hae-Young et al. (2011) Renal dysfunction in patients with thalassaemia. Br J Haematol 153:111-7
Thompson, Alexis A; Cunningham, Melody J; Singer, Sylvia T et al. (2011) Red cell alloimmunization in a diverse population of transfused patients with thalassaemia. Br J Haematol 153:121-8
Morris, Claudia R; Kim, Hae-Young; Trachtenberg, Felicia et al. (2011) Risk factors and mortality associated with an elevated tricuspid regurgitant jet velocity measured by Doppler-echocardiography in thalassemia: a Thalassemia Clinical Research Network report. Blood 118:3794-802
Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru et al. (2011) Iron chelation adherence to deferoxamine and deferasirox in thalassemia. Am J Hematol 86:433-6
Sobota, A; Yamashita, R; Xu, Y et al. (2011) Quality of life in thalassemia: a comparison of SF-36 results from the thalassemia longitudinal cohort to reported literature and the US norms. Am J Hematol 86:92-5
Trachtenberg, Felicia; Foote, Dru; Martin, Marie et al. (2010) Pain as an emergent issue in thalassemia. Am J Hematol 85:367-70

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