Results of a Phase I trial indicate that subjects with sickle cell disease (SCD) treated with hydroxyurea (HU) experience significant and sustained weight gain. In this project, we will take advantage of the opportunity afforded by the Phase II Hydroxyurea Efficacy Trial to elucidate the etiology and tissue composition of the weight gain and to determine if HU therapy is accompanied by improvement in muscle function. the University of North Carolina and Duke University Medical Center anticipate enrolling 30 subjects in the Phase II trial, 15 each in the active drug arm and 15 in the placebo arm. We anticipate being able to enroll at least 24 of the subjects in this project. Each subject will undergo a battery of tests during a brief admission to the UNC GCRC on four occasions at 0, 6, 12, and 18 months of therapy. The tests will include measurements of basal energy expenditure by indirect calorimetry, body composition by dual energy x-ray absorptiometry (DEXA), and muscle function. Muscle function will be assessed by grip strength, anaerobic capacity using a 10 second Wingate cycle ergometer test, and aerobic capacity using a version of the Astrand and Rhyming cycle ergometer test. Other, secondary, data to be collected at each admission include food intake from food frequency questionnaires, 24-hour creatinine excretion, bioelectric impedance measurement of body composition, tricep skinfold thickness, and arm muscle circumference. Basal energy expenditure will also be determined at three months to learn whether there is a fall in basal energy expenditure prior to substantial weight gain. We hypothesize that subjects who gain weight during treatment with HU will gain approximately 50% fat and 50% lean and that there will be a significant increase in muscle function. If this can be substantiated then treated SCD patients can anticipate a better quality of life, less likelihood of musculoskeletal injuries, improved physical work capacity, and improved job performance. If most of the weight gain is adipose tissue and muscle function does not improve, it will suggest that physical therapy and perhaps increased dietary protein intake during HU therapy may be beneficial. By elucidating the etiology and composition of the weight gain occurring during HU therapy and the effect of therapy on muscle function, this study will add significantly to an understanding of the metabolic effects responsible for the promising efficacy of this therapy.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Comprehensive Center (P60)
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Duke University
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Ariens, Robert A S; Lai, Thung-Shenq; Weisel, John W et al. (2002) Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms. Blood 100:743-54
Ware, Russell E; Eggleston, Barry; Redding-Lallinger, Rupa et al. (2002) Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy. Blood 99:10-4
Thompson Jr, Robert J; Gustafson, Kathryn E; Bonner, Melanie J et al. (2002) Neurocognitive development of young children with sickle cell disease through three years of age. J Pediatr Psychol 27:235-44
Slaughter, T F; Sreeram, G; Sharma, A D et al. (2001) Reversible shear-mediated platelet dysfunction during cardiac surgery as assessed by the PFA-100 platelet function analyzer. Blood Coagul Fibrinolysis 12:85-93
Lai, T S; Hausladen, A; Slaughter, T F et al. (2001) Calcium regulates S-nitrosylation, denitrosylation, and activity of tissue transglutaminase. Biochemistry 40:4904-10
Ataga, K I; Orringer, E P (2000) Renal abnormalities in sickle cell disease. Am J Hematol 63:205-11
Ataga, K I; Orringer, E P (2000) Bone marrow necrosis in sickle cell disease: a description of three cases and a review of the literature. Am J Med Sci 320:342-7
Kinney, T R; Helms, R W; O'Branski, E E et al. (1999) Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Blood 94:1550-4
Lai, T S; Slaughter, T F; Peoples, K A et al. (1999) Site-directed mutagenesis of the calcium-binding site of blood coagulation factor XIIIa. J Biol Chem 274:24953-8
Slentz-Kesler, K A; Hale, L P; Kaufman, R E (1998) Identification and characterization of K12 (SECTM1), a novel human gene that encodes a Golgi-associated protein with transmembrane and secreted isoforms. Genomics 47:327-40

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