BABY HUG

BABY HUG Manuscripts

Wang WC, Pavlakis SG, Helton KJ, McKinstry RC, Casella JC, Rees RC. (2008) MRI abnormalities in the brain in one-year-old children with sickle cell anemia. Pediatric Blood and Cancer, 51. 643-646.

Miller ST, Wang WC, Iyer R, Rana S, Lane P, Ware RE, Li D, Rees RC, Clinical Trials & Surveys Corporation, for the BABY HUG Investigators. Urine concentrating ability in infants with sickle cell disease: Baseline data from the phase III trial of hydroxyurea (BABY HUG). Pediatr Blood Cancer 54:265-268, February 2010.

Thompson BW, Rogers ZR, Miller ST, Rees RC, Ware RE, Waclawiw MA, Iyer RV, Casella JF, Luchtman-Jones L, Rana S, Thornburg CD, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik S, Howard TH, Luck L, Wang WC. The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG): Challenges of Study Design. Pediatr Blood Cancer 54:250-255, February 2010.

Pavlakis SG, Rees RC, Huang X, Brown RC, Casella JF, Iyer RV, Kalpatthi R, Luden J, Miller ST, Rogers ZR, Thornburg CD, Wang WC, Adams RJ, for the BABY HUG Investigators. Transcranial Doppler ultrasonography (TCD) in infants with sickle cell anemia: Baseline data from the BABY HUG Trial. Pediatr Blood Cancer 54:256-259, February 2010.

Thornburg CD, Rogers ZR, Jeng MR, Rana SR, Iyer RV, Faughnan L, Hassen L, Marshall J, McDonald RP, Wang WC, Huang X, Rees RC for the BABY HUG Investigators. Adherence to study medication and visits: Data from the BABY HUG Trial. Pediatr Blood Cancer 54:260-264, February 2010.

Ware RE, Rees RC, Sarnaik I, Iyer R, Alvarez OA, Casella JF, Shulkin BL, Shalaby-Rana E, Strife CF, Miller JH, Lane PA, Wang WC, Miller ST and the BABY HUG Investigators. Renal Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. J Pediatr 156:66-70, January 2010.

Recruitment of Infants with Sickle Cell Anemia to a Phase III Trial: Data from the BABY HUG Study Lynn Wynn, Scott Miller, Lane Faughnan, Zhaoyu Luo, Ellen Debenham, Billie Fish, Tally Hustace, Tracy Kelly, MaryLou MacDermott, Joan Marasciulo, Jennifer Marshall, Brenda Martin, Jennifer McDuffie, Mary Murphy, Betsy Rackoff, Caroline Reed, Phillip Seaman, Glenda Thomas, Winfred Wang. In Press.

Abdominal Ultrasound Findings in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. M Beth McCarville, Zhaoyu Luo, Xiangke Huang, Renee C Rees, Zora R Rogers, Ram Kalpatthi, Scott T Miller, Bruce Thompson Winfred C Wang. Submitted.

Scott T. Miller, MD, Russell E. Ware, MD, PhD, Ofelia A. Alvarez, MD, Xiangke Huang MD, MS, Zhaoyu Luo, PhD, Bruce Thompson, PhD, Rathi V. Iyer, MD, Zora R. Rogers, MD, Sharada A. Sarnaik, MD, Sohail R. Rana, MD, Peter A. Lane Jr., MD, Abdullah Kutlar, MD, Renee C. Rees, PhD, Winfred Wang MD and the BABY HUG Investigators. Serum Cystatin C Levels in Infants with Sickle Cell Anemia: Baseline data from BABY HUG. Submitted.

Zora R. Rogers MD, Winfred C Wang MD, Zhaoyu Luo PhD, Rathyi Iyer MD, Eglal Shalaby-Rana MD, Stephen Dertinger MD, Bea Files MD, Peter Lane MD, Bruce Thompson PhD, Scott T. Miller MD, and Russell E. Ware MD PhD, Barry L. Shulkin MD MBA and John H Miller MD. Biomarkers of Splenic Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. Submitted.

Winfred C Wang; Russell E Ware; Scott T Miller; Rathi V Iyer; James F Casella; Caterina P Minniti; Sohail Rana; Courtney D Thornburg; Zora R Rogers; Ram V Kalpatthi; Julio C Barredo; R Clark Brown; Sharada A Sarnaik; Thomas H Howard; Lynn W Wynn; Abdullah Kutlar; F Daniel Armstrong; Beatrice A Files; Jonathan C Goldsmith; Myron A Waclawiw; Xiangke Huang; and Bruce W Thompson for the BABY HUG Investigators. A multicenter randomised controlled trial of hydroxyurea (hydroxycarbamide) in very young children with sickle cell anaemia. Submitted.

BABY HUG Abstracts Presented

Wang W, Rees R, Li D, Rogers ZR, Iyer R, Rana S, Barredo J, Casella J, Driscoll C, Toledano S, Miller S, Zimmerman S, Miller J, Shalaby-Rana E, Thompson B, Bonds DR, Ware RE. Evaluation of renal function by glomerular filtration rate (GFR) in infants with sickle cell anemia. 46th Annual Meeting, ASH, San Diego CA, December 2004 (poster). Blood 2004;104:465a.

Rogers ZR, Rees RR, Wang WC, Li D, Iyer RV, Rana S, Barredo JC, Casella JF, Driscoll C, Toledano S, Miller ST, Zimmerman SA, Miller JH, Shalaby-Rana E, Dertinger SD, Thompson B, Ware RE. Evaluation of splenic function in infants with sickle cell anemia in the BABY HUG Trial. 46th Annual Meeting, ASH, San Diego CA, December 2004 (poster).

Rogers ZR, Rees RR, Wang WC, Li D, Iyer RV, Rana S, Barredo JC, Casella JF, Driscoll C, Toledano S, Miller ST, Zimmerman SA, Miller JH, Shalaby-Rana E, Dertinger SD, Thompson B, Ware RE. Evaluation of splenic function in infants with sickle cell anemia in the BABY HUG Trial. 28th Annual Meeting of the National Sickle Cell Disease Program, Cincinnati OH, April 2005. Blood 2004;104:975a.

Armstrong FD, Rees RC, Li D, Bonner M, Elkin D, Strouse JJ, Brown C, Wang W, for the Investigators of the Pediatric Clinical Trial of Hydroxyurea in Sickle Cell Anemia (BABY HUG). Baseline developmental function by age for children in the Pediatric Hydroxyurea Phase III Clinical Trial (Baby Hug). 28th Annual Meeting of the National Sickle Cell Disease Program, Cincinnati OH, April 2005.

Adams RJ, Luden J, Miller ST, Wang WC, Rees RC, Li D, Rogers Z, Brown C, Casella J, Zimmerman S.TCD in infants treated with hydroxyurea: interim report from BABY HUG study. 28th Annual Meeting of the National Sickle Cell Disease Program, Cincinnati OH, April 2005.

Casella JF, Wang WC, Rogers ZR, Rees RC, Iyer RV, Rana S, Driscoll MC, Miller ST, Toledano S, Barredo J, Zimmerman SA, Li D, Ware RE, Thompson B. Progress of the multicenter trial of hydroxyurea in infants with sickle cell anemia (BABY HUG) and assessment of baseline splenic and renal function. ASPHO/PAS, Washington DC, May 2005. Pediatr Blood Cancer 2005;44:551.

Rogers ZR, Thompson B, Ware RE, Wang WC, Iyer RV, Miller ST, Minniti C, Rana S, Barredo JC, Toledano S, Casella JF, Zimmerman SA, Files BA, Waclawiw M, Bonds DR. Pharmacokinetics of hydroxyurea in young children with sickle cell anemia: a report from the BABY HUG Trial. Blood 2005;106:890a.

Adams RJ, Barredo J, Bonds DR, Brown RC, Casella JF, Li D, Gerber AR, Iyer R, Luden J, Miller S, Minniti C, Rana S, Rees R, Rogers ZR, Toledano S, Wang W, Ware R, Sherri Zimmerman S. TCD in infants: a report from the BABY HUG trial. Blood 2005;106:280a.

Miller S, Barredo J, Brown CR, Bonds DR, Casella JF, Li D, Rees R, Thompson B, Gerber RA, Iyer R, Minniti C, Rana S, Rogers, ZR, Toledano S, Wang W, Ware R, Zimmerman S. Renal concentrating ability in infants with sickle cell anemia; preliminary data from BABY HUG, a multicenter trial. Renal and Urology Complications in Sickle Cell Disease Workshop, Annual Sickle Cell Disease Clinical Research Meetings, National Institutes of Health Campus, Bethesda Maryland, August 29, 2005.

Ware RE, Miller ST, Rees RC, Iyer RV, Rogers ZR, Zimmerman SA, Minniti C, Barredo J, Rana S, Casella J, Toledano S, Li D, Thompson B, Wang WC. Assessment of renal function in the Phase III Multicenter Hydroxyurea (BABY HUG) Trial for Infants with Sickle Cell Anemia. Renal and Urology Complications in Sickle Cell Disease Workshop, Annual Sickle Cell Disease Clinical Research Meetings, National Institutes of Health Campus, Bethesda Maryland, August 29, 2005.

Wang W, Helton KJ, Pavlakis SG, McKinstry RC, Adams RJ, Casella JF, Ichord RN, Li D, Rees RC. MRI abnormalities are present in one year-old children with sickle cell anemia. 29th Annual Meeting of the National Sickle Cell Disease Program, Memphis TN, April 2006.

Miller S, Barredo J, Brown RC, Bonds DR, Casella JF, Li D, Rees R, Thompson B, Gerber AR, Iyer R, Minniti C, Rana S, Rogers ZR, Toledano S, Wang W, Ware R, Zimmerman S. Renal concentrating ability in infants with sickle cell anemia; baseline data from BABY HUG, a multicenter trial. 29th Annual Meeting of the National Sickle Cell Disease Program, Memphis TN, April 2006.

Rogers ZR, Capparelli EV, Thompson B, Ware RE, Wang WC, Iyer RV, Miller ST, Minniti C, Rana S, Barredo JC, Toledano S, Zimmerman SA, Casella JF, Files BA, Waclawiw MA, Gerber AR. Pharmacokinetics of hydroxyurea in young children with sickle cell anemia: a report from the BABY HUG Trial. 29th Annual Meeting of the National Sickle Cell Disease Program, Memphis TN, April 2006.

Wynn L, Debenham E, Faughnan L, Martin B, Kelly T, Reed C, Seaman P, Miller S, Hustace T, Thomas G, Cochran C, Daner L, Wang W, Rees R. Recruitment in the BABY HUG Pediatric Hydroxyurea Phase III Clinical trial. 35th Anniversary Convention of the National Sickle Cell Disease Program and the Sickle Cell Disease Association of America, Inc. Washington DC, September 2007. Abstract #302 (poster).

Ware RE, Rees RC, Sarnaik I, Iyer R, Alvarez O, Casella JF, Shulkin B, Shalaby-Rana E, Strife CF, Miller JH, Lane PA, Wang WC, Miller ST for the BABY HUG Investigators. Renal function in infants with sickle cell anemia: baseline data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Blood 2008:112:1414 (poster).

Miller ST, Wang WC, Iyer R, Rana S, Lane P, Ware RE, Rees RC for the BABY HUG Investigators. Urine concentrating ability in infants with sickle cell anemia: baseline data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Blood 2008:112:1413 (poster).

Wynn L, Faughnan L, Li D, Wang WC, Martin B, Kelly T, Reed C, Seaman P, Marasciulo J, Rackoff B, Miller ST, Hustace T, Thomas G, Marshall J, McDuffie J, MacDermott M, Debenham E, Murphy M, Rees RC for the BABY HUG Investigators. Recruitment of infants with sickle cell anemia to a Phase III Trial: data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Blood 2008:112:1429 (poster).

Thornburg CD, Rogers ZR, Wang WC, Jeng M, Rana SR, Iyer RV, Faughnan L, Marshall J, Hassen L, MdDonald R, Rees RC for the BABY HUG Investigators. Study Drug and Visit Adherence: Data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Abstract #380 (poster).

Rogers ZR, Rees RC, Files B, Iyer RV, Shulkin B, Shalaby-Rana E, Miller J, Dertinger SD, Lane PA, Wang WC, Ware RE for the BABY HUG Investigators. Spleen Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Abstract #521 (poster).

Wang WC, Rees RC, Miller ST, Brown RC, Casella JF, Iyer R, Kalpatthi R, Luden J, Rogers ZR, Thornburg C, Adams RJ, Pavlakis S for the BABY HUG Investigators. Transcranial Doppler (TCD) ultrasonography in infants with sickle cell anemia: baseline data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Blood 2008:112:1436.

Armstrong FD, Elkin D, Brown C, Glass P, Rees RC, Wang WC for the BABY HUG Investigators. Neurodevelopment in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Blood 2008:112:265.

Zora R. Rogers, Renee C Rees, Beatrice Files, Rathi V. Iyer, Barry L Shulkin, Eglal Shalaby-Rana, John H Miller, Stephen D Dertinger, Peter A Lane, Winfred C Wang, Russell E Ware and the BABY HUG Investigators. Spleen Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG trial. Annual SCD Scientific Meeting, Ft. Lauderdale, FL. February 2009.

Wang WC, Wynn LW, Thornburg C. Recruitment and adherence in a phase III trial: lessons from the BABY HUG Study. Revista Brasileira de Hematologia e Hemoterapia 31(4):21, 2009.

McCarville MB, Rees RC, Rogers ZR, Kalpatthi R, Miller ST, Wang WC for the BABY HUG Investigators. Abdominal ultrasound findings in infants with sickle cell anemia: Baseline data from the BABY HUG Trial. Annual SCD Scientific Meeting, Ft. Lauderdale, FL. February 2009. (presented by Dr. Wang)

Scott T. Miller MD, Winfred Wang MD, Bruce Thompson PhD, for the BABY HUG Investigators. Should all infants with sickle cell anemia take hydroxyurea? Leicester abstract

Wang WC for the BABY HUG Investigators. Does Hydroxyurea Prevent Organ Dysfunction in Infants? Results from the BABY HUG Study. 4th Annual National SCD Scientific Meeting, Hollywood, FL. February 2010. (presented by Dr. Wang)

Miller ST for the BABY HUG Investigators. The Phase III Trial of Hydroxyurea in Infants with Sickle Cell Disease (BABY HUG): Issues and Implications. Sickle Cell: The Next 100 Years, De Montfort University, Leicester, United Kingdom, April 14-16, 2010. (presented by Dr. Miller)

Wang WC, Thompson B for the BABY HUG Investigators. Hydroxyurea treatment of infants with sickle cell anemia: results of the BABY HUG Study. American Society of Pediatric Hematology/Oncology, Montreal, Canada, April 2010.

Ware RE for the BABY HUG Investigators. Hydroxyurea for Infants with Sickle Cell Anemia: Results of the Phase III BABY HUG Trial. 1st Global Congress on Sickle Cell Disease. Accra, Ghana, July 20-23, 2010.

Lebensburger J, et al. Influence of Hemoglobin Phenotype in Infants with Sickle Cell Anemia: Results of the BABY HUG Study. Submitted to ASH.


BABY HUG Study Summary

BABY HUG is a randomized, double-blind multi-center clinical trial designed to enroll 200 patients between the ages of nine and seventeen months with sickle cell anemia. Each patient was assigned to treatment with hydroxyurea or placebo. The study is currently in a follow-up only phase; enrollment ended in September 2007. The primary analysis will be based on the detection of evidence of end organ damage (two organs of anticipated interest are the kidney and spleen) taking death, bone marrow transplantation and chronic transfusion into account as treatment failures. Treatment and follow-up will last two years. Double blinding of the assignment to hydroxyurea or placebo and medical treatment will be enhanced by the use of a Primary Endpoint Person at each Clinical Center to monitor local CBC results. Determination of the presence or absence of chronic end organ damage (either directly evidenced or inferred from surrogate measures) will be the responsibility of Endpoint Adjudication Panels composed of pediatric sub-specialists and sickle cell anemia expert(s) to be convened by the Medical Coordinating Center. The Endpoint Adjudication Panels will be provided complete clinical and laboratory documentation relevant to the classification of patient outcomes by the Medical Coordinating Center with attention to the blinding of personal identifying information and of treatment assignment information. BABY HUG is conducted by the collaborating investigators of the Medical Coordinating Center (MCC), affiliated Core Laboratories, and 14 Clinical Centers; the National Heart, Lung, and Blood Institute (NHLBI) Project Office in the Division of Blood Diseases and Resources (Sickle Cell Scientific Research Group); the National Institute of Child Health and Human Development (NICHD) Program Office; and a Pharmacy Distribution Center. A Data and Safety Monitoring Board (DSMB) has been appointed by the NHLBI and serves in an advisory capacity to the Director of the NHLBI, providing recommendations based on study performance, interim and final analyses.

Acknowledgments	Publications

CNMC M. Catherine Driscoll, Principal Investigator Barbara Speller-Brown, Coordinator Brenda Martin, Coordinator Penny Glass, Neuropsychologist Kimberly Krohn, Neurologist Cynthia Jiles, Pharmacist Jonise Handy, PEP Tammy Tsuchida, Neurologist Taeun Chang, Neurologist Caterina Minniti, Prinicpal Investigator Melissa O'Connell, Neuropsychologist Christine Heath, Neurologist Romuladus Azine, Data Manager Deepika Darbari, Co-Investigator LaShaun Washington-Batts, Pharmacist Jessica Carpenter, Neurology Lori Luchtman-Jones, Principal Investigator Ana Burgos, Co-Investigator DUKE Russell Ware, Principal Investigator William Schultz, Coordinator Jacqueline Davis, Coordinator Melanie Bonner, Neuropsychologist Rose-Mary Boustany, Neurologist Christina Johnson, Pharmacist Sherri A. Zimmerman, Principal Investigator Tracy Kelly, Coordinator Qi Chen, Data Manager Courtney Thornburg, Principal Investigator Amanda Mandy, Data Manager Natalia Dixon, Co-PI, PEP Jane Millen, Pharmacist Daniel Wechsler, Co-PI Shelly Burgett, PEP Pedro Weisleder, Neurologist William Gallentine, Neurology Michael Armstrong, Co-PI Kathleen Greenwell, Staff Assistant DUKE Sohail Rana, M.D., Principal Investigator Khahn Nguyen, Pharmacist Caroline Reed, F.N.P., Coordinator Patricia Houston, M.S., PEP Erin Yeagley, F.N.P. PEP JHU James Casella, Principal Investigator Cathy O'Haver, Coordinator Sue Dixon, Coordinator Loretta Ash, Coordinator Theodore A Zabel, Neuropsychologist Kaleb Yohay, Neurologist Kathleen Truelove, Pharmacist Phillip Seaman, Co-Investigator; Coordinator Jeffrey Keefer, Primary Endpoint Person Lori Jordan, Neurologist Christiane Cox, Neuropsychologist David Lieberman, Neurologist Cynthia Smith, Neuropsychologist Patrice Sharp, Coordinator/Data Manager Kim Coppage, data manager GEORGETOWN Aziza Shad, Principal Investigator Corina Gonzalez, Co-Investigator; Principal Investigator Anjum Zaki, Coordinator Katherine Mying-Hpu, Coordinator Ravie Kem, Pharmcist SINAI Joseph Wiley, Co-Investigator Jason Fixler, Principal Investigator Joan Marasciulo, Coordinator Mekdese Kassa, Pharmacist Linda Hultgren, Pharmacist MUSC Julio Barredo, Principal Investigator R. Clark Brown, Co-Investigator Ellen Debenham, Coordinator Deborah Disco, Co-Investigator Sherron Jackson, Co-Investigator Pamela Ingram, Neuropsychologist David A. Griesemer, Neurologist Kimberly Porter, Pharmacist Jessica Peterson, PEP/Local Lab Reader Shayla Bergman, Co-Investigator Stacey Ribble, PEP/Local Lab Reader Betsy Rackoff, Coordinator Mary Ellen Cavalier, Principal Investigator Ram Kalpatthi, Principal Investigator Lisa Kuisel, PEP ST. JUDE Winfred Wang, Principal Investigator Russell Ware, Co-Investigator Lynn Wynn, Coordinator Susan Strawn, Coordinator Charlotte Fineburg-Buchner, Neuropsychologist Raja Khan, Neurologist Julie Richardson, Pharmacist Lane Faughnan, Coordinator Susan Carr, Pharmacist Letitia Williams, Primary Endpoint Person Brannon Morris, Neurologist SUNY Scott Miller, Principal Investigator Sreedhar P. Rao, Co-Investigator Sandra Graham, Coordinator Joan Hittleman, Neuropsychologist Geetha Chari, Neurologist Motria Mishko, Pharmacist Kathy Rey, Primary Endpoint Person Arnold Strashun, Nuclear Medicine Rebecca S. Gonzalez, CNMT MIAMI Charles Pegelow, Principal Investigator Stuart Toledano, Principal Investigator F. Daniel Armstrong, Co-Investigator Tally Hustace, Coordinator Jacqueline Levy, Neuropsychologist Robert Lopez, Neurologist Raul Pino, Pharmacist Dale Wright, Primary Endpoint Person Brandon Briery, Neuropsychologist Noeline Lewis, Primary Endpoint Person Winsome Thompson, Neuropsychologist Ellen White, Primary Endpoint Person Nancy Simon, Pharmacist Julio Barredo, Principal Investigator Ofelia Alvarez, Co-Investigator UMMC Rathi Iyer, Principal Investigator Mary Gail Smith, Co-Investigator Sheryl Hand, Coordinator Teresa Walker, Coordinator/Back-up PEP David Elkin, Neuropsychologist V.V. Vedanarayanan, Neurologist Stephen Oubre, Pharmacist Cindy Kendig, Coordinator (PEP) Glenda Thomas, Coordinator Clay Rouse, Pharmacist Todd Hovas, Pharmacist Laura Coleman, Pharmacist Betsy Herrington, PEP Deborah Estess, Coordinator Maria Thames, Neuropsychologist Tammy Roberts, PEP Tobi Breland BSN, MSN, APRN - BC Amy Forsythe, BSN, MSN, NP - C Tom Hogan RT, RDMS Gloria Bishop, PEP UTSW Zora R. Rogers, Principal Investigator Cindy Cochran, Coordinator Nicole Corrigan, Data Manager Cheryl Silver, Neuropsychologist Michael Dowling, Neurologist Leah Adix, Coordinator Staci Horvath, Coordinator Claudette Vicks, Coordinator Niechelle Loyd, PEP/Data Manager Elizabeth Shull, Coordinator Jennifer Marshall, Coordinator Roxana Mars, Coordinator Sandra Richardson, PEP Katherine Montefiore, Pharmacist Terri Burrows, Pharmacist Sonia Gonzales, Pharmacist Ruth Merryman, Pharmacist UAB Thomas Howard, Principal Investigator Holly Bryan, Coordinator Roger Berkow, PEP Avi Madan-Swain, Neuropsychologist Alyssa Reddy, Neurologist Kathleen Blair, Pharmacist Jennifer DeBerry-McDuffie, Coordinator Roy McDonald, Coordinator Kerry Parsons, Pharmacist Hucks Buchanan, Pharmacist Kimberly Whelan, PEP April Holloway, Pharmacist DREXEL Carlton Dampier, Principal Investigator Mary Lou MacDermott, Coordinator Nina Anderson, Back-up Coordinator Maureen Meier, PEP Lori Luck, Principal Investigator Michele Cahill, PEP Mitzie Grant, Neuropsychologist Sanjeer Kothare, Neurologist Janet Azizi, Pharmacist William Choi, Pharmacist Karen Carvalho, Neuorologist Frank Shafer- Interim Principal Investigator Norma Lerner, Principal Investigator EMORY Peter Lane, Principal Investigator Clark Brown, Principal Investigator Ellen Debenham, Coordinator Terrell Faircloth, Coordinator Alcuin Johnson, Neuropsychologist Bryan Philbrook, Neurologist Laura Greve, Neuropsychologist Tamara New-Bailey, Co-Investigator Leann Hassen, PEP James Rhodes, Pharmacist Ifeyinwa Osunkwo, Co-Investigator Korin Cherry, PEP Betsy Record, Coordinator Janet Patton, Neuropsychologist WAYNE STATE Sharada Sarnaik, Principal Investigator Wanda Whitten-Shurney, Co- PI Mary Murphy, Coordinator Monica Malian, Pharmacist Jocelyn McCrae, Neuropsychologist Marianne Majkowski, Neurologist Madhvi Rajpurkar, PEP Jamal Ameli, Data Manager/ PEP Kristin Storie-Kennedy, PEP Ordella Henderson, Coordinator Meera Chitlur, Co-Investigator U OF MD Neil Grossman, Principal Investigator Christine Rhoad, Coordinator Brian Howard, Data Manager Mari B. Rodrigues, Coordinator Haiyan Jiang, Pharmacist MCC Franca Barton Patrice Brock Kate Burkhardt Sandy Carberry Margie Carroll Judy Dotson Kai-Ing Duh Billie J. Fish Carol Fosse Mikhail Gordon Roman Gordon Joulia Haziminas Xiangke Huang Xuan Huang Michal Knight Daner Li Zhaoyu Luo Helene Lutz Anne Martien Sean McHale Charity Meyer Renee Rees Tia Ricks Archie Santos Michael Terrin Bruce Thompson Andrey Tsanko Stephanie Watford Patricia Wilkins Hean Zhuang NHLBI Henry Chang, M.D. Lynn Furtaw Jonathan Goldsmith, M.D. Sara Levy Harvey Luksenburg, M.D. Debi Spillan Myron Waclawiw, Ph.D. NICHD Donald Mattison, M.D. Anne Willoughby, M.D. Anne Zajicek, M.D. CONSULTANTS F. Daniel Armstrong, Ph.D. Beatrice Files, M.D. Michael Gelfand, M.D. Kathleen Helton, M.D. Rebecca N. Ichord, M.D. Michael Jeng, M.D. Thomas Kinney, M.D. Mary Elizabeth McCarville, M.D. Elias Melhem, M.D. John H. Miller, M.D. Steven Pavlakis, M.D. Howard A. Pearson, M.D. Allison Ross, M.D. George J. Schwartz, M.D. Eglal (Gila) Shalaby-Rana, M.D. Barry Shulkin, M.D., M.B.A. Millicent Sutton, M.D. TCD CORE LABORATORY Robert J. Adams, M.S., M.D. Nadine Odo Corinne Hilbert Judy Luden, CCRP Latonya Brown HEALTH & HUMAN SERVICE SUPPLY SERVICE CENTER Thomas Shaffer Michael Soler Annette Quinones, RPh Donna Bannon Dino Edwards HEMATOLOGY/BIOCHEMISTRY CORE LABORATORY Abdullah Kutlar, M.D. Betsy Clair Deborah Davis Niren Patel, MBBS Leslie Holley PITTED CELL CORE LABORATORY Beth Smith Judy Loftin Alexander Sozansky PENICILLIN URINE LABORATORY Doramarie Arocha CYTOGENETICS LABORATORY Anita Kulharya, Ph.D. Patricia Miller Karen Norris Satya Prakash DNA MUTATIONS CORE LABORATORY Russell E. Ware, MD Ph.D. Stephen Dertinger, Ph.D. Thad Howard, M.S. Jin He, M.D. Jonathan M. Flanagan, Ph.D. IMMUNOLOGY CORE LABORATORY Howard Lederman, M.D., Ph.D. Michael Borowitz, M.D., Ph.D. Kathy Cowan Patricia Chivrazzi Andrea Swift Thomas Quinn PERCEPTIVE INFORMATICS, INC. Marie Luby PK COORDINATING CENTER Frank Norton, Ph.D.	BABY HUG Manuscripts Wang WC, Pavlakis SG, Helton KJ, McKinstry RC, Casella JC, Rees RC. (2008) MRI abnormalities in the brain in one-year-old children with sickle cell anemia. Pediatric Blood and Cancer, 51. 643-646. Miller ST, Wang WC, Iyer R, Rana S, Lane P, Ware RE, Li D, Rees RC, Clinical Trials & Surveys Corporation, for the BABY HUG Investigators. Urine concentrating ability in infants with sickle cell disease: Baseline data from the phase III trial of hydroxyurea (BABY HUG). Pediatr Blood Cancer 54:265-268, February 2010. Thompson BW, Rogers ZR, Miller ST, Rees RC, Ware RE, Waclawiw MA, Iyer RV, Casella JF, Luchtman-Jones L, Rana S, Thornburg CD, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik S, Howard TH, Luck L, Wang WC. The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG): Challenges of Study Design. Pediatr Blood Cancer 54:250-255, February 2010. Pavlakis SG, Rees RC, Huang X, Brown RC, Casella JF, Iyer RV, Kalpatthi R, Luden J, Miller ST, Rogers ZR, Thornburg CD, Wang WC, Adams RJ, for the BABY HUG Investigators. Transcranial Doppler ultrasonography (TCD) in infants with sickle cell anemia: Baseline data from the BABY HUG Trial. Pediatr Blood Cancer 54:256-259, February 2010. Thornburg CD, Rogers ZR, Jeng MR, Rana SR, Iyer RV, Faughnan L, Hassen L, Marshall J, McDonald RP, Wang WC, Huang X, Rees RC for the BABY HUG Investigators. Adherence to study medication and visits: Data from the BABY HUG Trial. Pediatr Blood Cancer 54:260-264, February 2010. Ware RE, Rees RC, Sarnaik I, Iyer R, Alvarez OA, Casella JF, Shulkin BL, Shalaby-Rana E, Strife CF, Miller JH, Lane PA, Wang WC, Miller ST and the BABY HUG Investigators. Renal Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. J Pediatr 156:66-70, January 2010. Recruitment of Infants with Sickle Cell Anemia to a Phase III Trial: Data from the BABY HUG Study Lynn Wynn, Scott Miller, Lane Faughnan, Zhaoyu Luo, Ellen Debenham, Billie Fish, Tally Hustace, Tracy Kelly, MaryLou MacDermott, Joan Marasciulo, Jennifer Marshall, Brenda Martin, Jennifer McDuffie, Mary Murphy, Betsy Rackoff, Caroline Reed, Phillip Seaman, Glenda Thomas, Winfred Wang. In Press. Abdominal Ultrasound Findings in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. M Beth McCarville, Zhaoyu Luo, Xiangke Huang, Renee C Rees, Zora R Rogers, Ram Kalpatthi, Scott T Miller, Bruce Thompson Winfred C Wang. Submitted. Scott T. Miller, MD, Russell E. Ware, MD, PhD, Ofelia A. Alvarez, MD, Xiangke Huang MD, MS, Zhaoyu Luo, PhD, Bruce Thompson, PhD, Rathi V. Iyer, MD, Zora R. Rogers, MD, Sharada A. Sarnaik, MD, Sohail R. Rana, MD, Peter A. Lane Jr., MD, Abdullah Kutlar, MD, Renee C. Rees, PhD, Winfred Wang MD and the BABY HUG Investigators. Serum Cystatin C Levels in Infants with Sickle Cell Anemia: Baseline data from BABY HUG. Submitted. Zora R. Rogers MD, Winfred C Wang MD, Zhaoyu Luo PhD, Rathyi Iyer MD, Eglal Shalaby-Rana MD, Stephen Dertinger MD, Bea Files MD, Peter Lane MD, Bruce Thompson PhD, Scott T. Miller MD, and Russell E. Ware MD PhD, Barry L. Shulkin MD MBA and John H Miller MD. Biomarkers of Splenic Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. Submitted. Winfred C Wang; Russell E Ware; Scott T Miller; Rathi V Iyer; James F Casella; Caterina P Minniti; Sohail Rana; Courtney D Thornburg; Zora R Rogers; Ram V Kalpatthi; Julio C Barredo; R Clark Brown; Sharada A Sarnaik; Thomas H Howard; Lynn W Wynn; Abdullah Kutlar; F Daniel Armstrong; Beatrice A Files; Jonathan C Goldsmith; Myron A Waclawiw; Xiangke Huang; and Bruce W Thompson for the BABY HUG Investigators. A multicenter randomised controlled trial of hydroxyurea (hydroxycarbamide) in very young children with sickle cell anaemia. Submitted. BABY HUG Abstracts Presented Wang W, Rees R, Li D, Rogers ZR, Iyer R, Rana S, Barredo J, Casella J, Driscoll C, Toledano S, Miller S, Zimmerman S, Miller J, Shalaby-Rana E, Thompson B, Bonds DR, Ware RE. Evaluation of renal function by glomerular filtration rate (GFR) in infants with sickle cell anemia. 46th Annual Meeting, ASH, San Diego CA, December 2004 (poster). Blood 2004;104:465a. Rogers ZR, Rees RR, Wang WC, Li D, Iyer RV, Rana S, Barredo JC, Casella JF, Driscoll C, Toledano S, Miller ST, Zimmerman SA, Miller JH, Shalaby-Rana E, Dertinger SD, Thompson B, Ware RE. Evaluation of splenic function in infants with sickle cell anemia in the BABY HUG Trial. 46th Annual Meeting, ASH, San Diego CA, December 2004 (poster). Rogers ZR, Rees RR, Wang WC, Li D, Iyer RV, Rana S, Barredo JC, Casella JF, Driscoll C, Toledano S, Miller ST, Zimmerman SA, Miller JH, Shalaby-Rana E, Dertinger SD, Thompson B, Ware RE. Evaluation of splenic function in infants with sickle cell anemia in the BABY HUG Trial. 28th Annual Meeting of the National Sickle Cell Disease Program, Cincinnati OH, April 2005. Blood 2004;104:975a. Armstrong FD, Rees RC, Li D, Bonner M, Elkin D, Strouse JJ, Brown C, Wang W, for the Investigators of the Pediatric Clinical Trial of Hydroxyurea in Sickle Cell Anemia (BABY HUG). Baseline developmental function by age for children in the Pediatric Hydroxyurea Phase III Clinical Trial (Baby Hug). 28th Annual Meeting of the National Sickle Cell Disease Program, Cincinnati OH, April 2005. Adams RJ, Luden J, Miller ST, Wang WC, Rees RC, Li D, Rogers Z, Brown C, Casella J, Zimmerman S.TCD in infants treated with hydroxyurea: interim report from BABY HUG study. 28th Annual Meeting of the National Sickle Cell Disease Program, Cincinnati OH, April 2005. Casella JF, Wang WC, Rogers ZR, Rees RC, Iyer RV, Rana S, Driscoll MC, Miller ST, Toledano S, Barredo J, Zimmerman SA, Li D, Ware RE, Thompson B. Progress of the multicenter trial of hydroxyurea in infants with sickle cell anemia (BABY HUG) and assessment of baseline splenic and renal function. ASPHO/PAS, Washington DC, May 2005. Pediatr Blood Cancer 2005;44:551. Rogers ZR, Thompson B, Ware RE, Wang WC, Iyer RV, Miller ST, Minniti C, Rana S, Barredo JC, Toledano S, Casella JF, Zimmerman SA, Files BA, Waclawiw M, Bonds DR. Pharmacokinetics of hydroxyurea in young children with sickle cell anemia: a report from the BABY HUG Trial. Blood 2005;106:890a. Adams RJ, Barredo J, Bonds DR, Brown RC, Casella JF, Li D, Gerber AR, Iyer R, Luden J, Miller S, Minniti C, Rana S, Rees R, Rogers ZR, Toledano S, Wang W, Ware R, Sherri Zimmerman S. TCD in infants: a report from the BABY HUG trial. Blood 2005;106:280a. Miller S, Barredo J, Brown CR, Bonds DR, Casella JF, Li D, Rees R, Thompson B, Gerber RA, Iyer R, Minniti C, Rana S, Rogers, ZR, Toledano S, Wang W, Ware R, Zimmerman S. Renal concentrating ability in infants with sickle cell anemia; preliminary data from BABY HUG, a multicenter trial. Renal and Urology Complications in Sickle Cell Disease Workshop, Annual Sickle Cell Disease Clinical Research Meetings, National Institutes of Health Campus, Bethesda Maryland, August 29, 2005. Ware RE, Miller ST, Rees RC, Iyer RV, Rogers ZR, Zimmerman SA, Minniti C, Barredo J, Rana S, Casella J, Toledano S, Li D, Thompson B, Wang WC. Assessment of renal function in the Phase III Multicenter Hydroxyurea (BABY HUG) Trial for Infants with Sickle Cell Anemia. Renal and Urology Complications in Sickle Cell Disease Workshop, Annual Sickle Cell Disease Clinical Research Meetings, National Institutes of Health Campus, Bethesda Maryland, August 29, 2005. Wang W, Helton KJ, Pavlakis SG, McKinstry RC, Adams RJ, Casella JF, Ichord RN, Li D, Rees RC. MRI abnormalities are present in one year-old children with sickle cell anemia. 29th Annual Meeting of the National Sickle Cell Disease Program, Memphis TN, April 2006. Miller S, Barredo J, Brown RC, Bonds DR, Casella JF, Li D, Rees R, Thompson B, Gerber AR, Iyer R, Minniti C, Rana S, Rogers ZR, Toledano S, Wang W, Ware R, Zimmerman S. Renal concentrating ability in infants with sickle cell anemia; baseline data from BABY HUG, a multicenter trial. 29th Annual Meeting of the National Sickle Cell Disease Program, Memphis TN, April 2006. Rogers ZR, Capparelli EV, Thompson B, Ware RE, Wang WC, Iyer RV, Miller ST, Minniti C, Rana S, Barredo JC, Toledano S, Zimmerman SA, Casella JF, Files BA, Waclawiw MA, Gerber AR. Pharmacokinetics of hydroxyurea in young children with sickle cell anemia: a report from the BABY HUG Trial. 29th Annual Meeting of the National Sickle Cell Disease Program, Memphis TN, April 2006. Wynn L, Debenham E, Faughnan L, Martin B, Kelly T, Reed C, Seaman P, Miller S, Hustace T, Thomas G, Cochran C, Daner L, Wang W, Rees R. Recruitment in the BABY HUG Pediatric Hydroxyurea Phase III Clinical trial. 35th Anniversary Convention of the National Sickle Cell Disease Program and the Sickle Cell Disease Association of America, Inc. Washington DC, September 2007. Abstract #302 (poster). Ware RE, Rees RC, Sarnaik I, Iyer R, Alvarez O, Casella JF, Shulkin B, Shalaby-Rana E, Strife CF, Miller JH, Lane PA, Wang WC, Miller ST for the BABY HUG Investigators. Renal function in infants with sickle cell anemia: baseline data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Blood 2008:112:1414 (poster). Miller ST, Wang WC, Iyer R, Rana S, Lane P, Ware RE, Rees RC for the BABY HUG Investigators. Urine concentrating ability in infants with sickle cell anemia: baseline data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Blood 2008:112:1413 (poster). Wynn L, Faughnan L, Li D, Wang WC, Martin B, Kelly T, Reed C, Seaman P, Marasciulo J, Rackoff B, Miller ST, Hustace T, Thomas G, Marshall J, McDuffie J, MacDermott M, Debenham E, Murphy M, Rees RC for the BABY HUG Investigators. Recruitment of infants with sickle cell anemia to a Phase III Trial: data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Blood 2008:112:1429 (poster). Thornburg CD, Rogers ZR, Wang WC, Jeng M, Rana SR, Iyer RV, Faughnan L, Marshall J, Hassen L, MdDonald R, Rees RC for the BABY HUG Investigators. Study Drug and Visit Adherence: Data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Abstract #380 (poster). Rogers ZR, Rees RC, Files B, Iyer RV, Shulkin B, Shalaby-Rana E, Miller J, Dertinger SD, Lane PA, Wang WC, Ware RE for the BABY HUG Investigators. Spleen Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Abstract #521 (poster). Wang WC, Rees RC, Miller ST, Brown RC, Casella JF, Iyer R, Kalpatthi R, Luden J, Rogers ZR, Thornburg C, Adams RJ, Pavlakis S for the BABY HUG Investigators. Transcranial Doppler (TCD) ultrasonography in infants with sickle cell anemia: baseline data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Blood 2008:112:1436. Armstrong FD, Elkin D, Brown C, Glass P, Rees RC, Wang WC for the BABY HUG Investigators. Neurodevelopment in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial. 50th Annual Meeting, ASH, San Francisco CA, December 2008. Blood 2008:112:265. Zora R. Rogers, Renee C Rees, Beatrice Files, Rathi V. Iyer, Barry L Shulkin, Eglal Shalaby-Rana, John H Miller, Stephen D Dertinger, Peter A Lane, Winfred C Wang, Russell E Ware and the BABY HUG Investigators. Spleen Function in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG trial. Annual SCD Scientific Meeting, Ft. Lauderdale, FL. February 2009. Wang WC, Wynn LW, Thornburg C. Recruitment and adherence in a phase III trial: lessons from the BABY HUG Study. Revista Brasileira de Hematologia e Hemoterapia 31(4):21, 2009. McCarville MB, Rees RC, Rogers ZR, Kalpatthi R, Miller ST, Wang WC for the BABY HUG Investigators. Abdominal ultrasound findings in infants with sickle cell anemia: Baseline data from the BABY HUG Trial. Annual SCD Scientific Meeting, Ft. Lauderdale, FL. February 2009. (presented by Dr. Wang) Scott T. Miller MD, Winfred Wang MD, Bruce Thompson PhD, for the BABY HUG Investigators. Should all infants with sickle cell anemia take hydroxyurea? Leicester abstract Wang WC for the BABY HUG Investigators. Does Hydroxyurea Prevent Organ Dysfunction in Infants? Results from the BABY HUG Study. 4th Annual National SCD Scientific Meeting, Hollywood, FL. February 2010. (presented by Dr. Wang) Miller ST for the BABY HUG Investigators. The Phase III Trial of Hydroxyurea in Infants with Sickle Cell Disease (BABY HUG): Issues and Implications. Sickle Cell: The Next 100 Years, De Montfort University, Leicester, United Kingdom, April 14-16, 2010. (presented by Dr. Miller) Wang WC, Thompson B for the BABY HUG Investigators. Hydroxyurea treatment of infants with sickle cell anemia: results of the BABY HUG Study. American Society of Pediatric Hematology/Oncology, Montreal, Canada, April 2010. Ware RE for the BABY HUG Investigators. Hydroxyurea for Infants with Sickle Cell Anemia: Results of the Phase III BABY HUG Trial. 1st Global Congress on Sickle Cell Disease. Accra, Ghana, July 20-23, 2010. Lebensburger J, et al. Influence of Hemoglobin Phenotype in Infants with Sickle Cell Anemia: Results of the BABY HUG Study. Submitted to ASH.