Bethesda, Maryland

November 1, 2004


Dr. Oswaldo Castro, Dr. Michael DeBaun, Dr. Johnson Haynes, Dr. Russell Ware, Dr. Theodore Wun, Dr. Gilda Barabino.


Dr. Paul Frenette, Dr. Dorothy Moore, Ms. J. Hoxi Jones.


Dr. Joseph DeSimone, Dr. Marie Mann


Dr. Robert Sheffler, Dr. William Hannon.


Shanese Baylor, MPH, HRSA, Dr. Duane Bonds, DBDR/BDP, Dr. Willarda Edwards, MBA, SCDAA, Dr. Gregory Evans, DBDR/BDP; Ms. Judith Hagopian, HRSA/MCHB/GSB, Dr. Blaine Moore DBDR/BDP; Dr. Charles Peterson, DBDR; Dr. Georgia Persinos, PG Associates, Ms. Susan Pucie, NHLBI/DBDR, Ms. Sonya Ross, SCDAA, Dr. Ellen Werner, DBDR/BDP., Dr. William P. Winter, Howard University, Mr. Jeffrey Young, The Blue Sheet

Executive Secretary - Dr. Charles M. Peterson

Secretary - Ms. Petronella A. Barrow

Dr. Barbara Alving, Acting Director NHLBI called the meeting to order at 8:30 am and led a discussion on the future of hemoglobinopathies research and care and the need to work together within the field to achieve common goals with special emphasis on the sickle cell and thalassemia communities. The group also noted that it was important to gather agencies such as AHQR, CDC, HRSA and others involved in these areas together to further the research and healthcare agendas. The hemophilia community also faces many common issues with the hemoglobinopathies and could be included in these outreach efforts. One example discussed was the documentation of the hemophiia community by CDC that has not occurred to the same extent in the sickle cell and thalassemia communities. All share a common need to educated the wider community and require special efforts of outreach to assure that participants and communities understand the importance of research and participation in protocols. One suggestion was to arrange a satellite meeting of agencies to the biannual Sickle Sell Disease Advisory Committee Meetings.

Dr. Peterson referred members to the required notification regarding conflicts of interest. He reminded those present to sign in on the required sign-in sheets.

  1. Dr. Ted Wun called for review of the minutes of June 4, 2004 and they were reviewed and approved.
  2. Dr. Wun welcomed the members and guests and introduced the Scientific Presentations.

    A. Dr. Michael DeBaun reviewed the Silent Cerebral infarct Trial (SITS).

    Silent cerebral infarct is the most common cause of severe neurological disease in children with sickle cell anemia, occurring in 22% of this population prior to their 18th birthday. The overall goal of this trial is to determine whether blood transfusion therapy will decrease further neurologic morbidity in children with silent cerebral infarcts, and if so, the magnitude of this benefit. We propose a multi-center randomized trial with 24 Clinical Sites, a Clinical Coordinating Center and a Statistical Coordinating Center to test the following hypothesis: prophylactic blood transfusion therapy in children with silent cerebral infarcts will result in at least an 86% reduction in the rate of subsequent overt strokes or new cerebral infarcts as defined by MRI of the brain. The intervention is blood transfusion therapy versus observation, with a goal to keep the maximum hemoglobin S concentration less than 30% in the transfused patients. Approximately 3020 children with sickle cell anemia, greater than 6 years of age and less than 13 years of age, will be eligible for screening evaluations. Among this group of eligible patients, approximately 1880 children will be asked to participate and will receive MRIs of the brain. In this group, we estimate that 376 children (20%) will have silent cerebral infarcts, among whom 38 children (10%) will have an elevated TCD measurement > 200 cm/sec and will not be eligible for the study. The remaining 338 children will be eligible for random allocation to either observation or blood transfusion therapy. Based on a 60% parent and child acceptance rate among children with silent cerebral infarcts, a study size of 203 participants (at least 101 in each treatment assignment) ensures 90% power to detect the effect necessary to make transfusion therapy worth recommending (86% reduction) after accounting for 10% drop out and 20% crossover rates. The standardization of the trial will occur during the first six months, enrollment for 24 months, and the intervention for 36 months. Twelve months after enrollment, each patient will receive a MRI and TCD. Each study participant will receive MRI and cognitive assessment at study exit (month 36 after enrollment). The primary aim of this trial is to determine the effectiveness of blood transfusion therapy for prevention of stroke or new silent cerebral infarct assessed by MRI of the brain. The secondary aims of this trial are determining whether: 1) prophylactic blood transfusion therapy will limit further decline in general intellectual abilities; and 2) the overall benefits of blood transfusion therapy for silent cerebral infarcts outweigh risks associated with this therapy in a formal risk benefit analysis. We anticipate results of this study could lead to a change in standard care practices for children affected with both sickle cell disease and silent cerebral infarcts.

    B. Dr. Mark Gladwin: presented an Update on Sildenafil for Pulmonary Hypertension A large scale treatment trial is being planned with sildenafil. Such an effort would require the collaboration of the intra- and extra-mural communities to assure adequate recruitment. The Committee continued to support that effort in view of the severity of the problem in sickle cell disease.

    C. Dr. Willarda Edwards presented an Update on the Sickle Cell Disease Association of America. The organization has recently moved its headquarters to: 16 S. Calvert Street; Suite 600; Baltimore, MD 21202

    There are now 63 membership organizations in 38 states. The Association strives to raise awareness, train more medical professions in the evidence based treatment of sickle cell disease and improve the medical care of these patients. Additional goals include sharing clinical trial opportunities with patients, families and professionals and build future partnerships. NHLBI was encouraged to continue to explore means by which it could partner with the Association.

  3. Chairman=s Report:: Dr Wun provided an update on the Working Group on an Adult Consultative Network. The concept of a network is making some progress despite the fact that there is little evidence based care that has been validated especially for the adult with sickle cell disease. The LISTSERV comprises approximately 130 people who use it as a forum for communication and problem solving. The groups will strive toward achieving best practice recommendations and a series of conferences are being planned. A liaison with ER physicians is being explored with an aim toward creating pain management guidelines. Reimbursement issues provide a continuing challenge toward providing the kind of care required for a comprehensive approach to a chronic disease such as sickle cell disease that targets an under served population. One suggestion discussed was whether the VA System might serve as a center for sickle cell care. With its geographic distribution and evolution toward critical care pathways approaches to illness, the VA might be able to address many of the problems inherent in providing care and facilitating research for the sickle cell population. The Committee felt that the idea should be explored further.

  4. The Action Item from previous meeting were completed. It was noted that rather the Committee complimented NHLBI on its responsiveness to suggestions from the Sickle Cell Disease Advisory Committee and its members.

  5. Update on Program Activities

    A. The New NHLBI Strategic Plan for Hemoglobin Disorders was reviewed by Dr. Evans. In response to the outcome of the NHGRI-led workshop, ANew Directions in Sickle Cell Therapy in the Genome Era,@ held in November, 2003. Starting with the over 30 workshop recommendations, this group identified 10 priority areas for the NIH to address, comprising a new NHLBI Strategic Plan for Hemoglobin Disorders from which initiatives may be developed in the future. Some of the priority areas overlap with those proposed and endorsed in 2000 by NHLBI as part of its Strategic Plan for a Gene-Based Cure for Beta-Chain Hemoglobinopathies, and some overlap with key areas or initiatives previously recommended by the NHLBI Sickle Cell Disease Advisory Committee. The 10 priority areas are:

    • E-Mail LISTSERV for sickle cell disease research This is available now by sending an e-mail to . Type as the body of the message: subscribe SCDR-L and your name.
    • Clinical research network focused on Phase III clinical trials for sickle cell disease (RFP or RFA). This is about ready to be announced.
    • International, prospective registry and sample repository to support large scale human genetic studies for sickle cell disease (RFP or RFA)
    • Training program for application of high-throughput genomic/proteomic technologies to hemoglobin disorders (RFA)
    • Chemical genomics for sickle cell disease (RFA; leverages related portion of the NIH Roadmap effort)
    • Research on ethical, legal, and social implications of human genetic studies for subjects with sickle cell disease (Notice in the Guide as addendum to existing Program Announcement)
    • Novel idea grants for sickle cell disease (PA)
    • Genetic modifiers of sickle cell disease (RFP or RFA;dependent on registry, with clinical phenotypes linked to DNA samples)
    • Late stage drug development for hemoglobin disorders (RFP or RFA; will leverage related portion of the NIH Roadmap effort to the extent feasible) 10- Gene therapy for hemoglobin disorders (RFA)

    B. Comprehensive Sickle Cell Centers Integration Committee Report : Dr. Evans reviewed the progress made by the centers, and the protocols under consideration.

    C. MSH Patients= Follow-up: Dr. Bonds noted that the follow-up study continued.

    D. Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) This trial has increased recruitment and is preparing to plan for the expansion phase. Several abstracts have been prepared for ASH.

    E. Stop II Trial: Dr. Bonds noted that the study was progressing.

    F. Health-related Quality of Life Dr. Werner mentioned that funding had been received to continue development of an instrument for adults. The Committee encouraged NHLBI to increase its efforts to quantify quality of life at all ages and stages of sickle cell disease. Such an effort is critical to the appropriate evaluation of clinical trials.

  6. Suggestions for NHLBI from the Committee

    The Committee recommended that the next major issue that needed to be addressed was that of Renal Complications of Sickle Cell Disease. It was realized that this was a large and multifaceted problem that might best be approached by one or a series of workshops.

  7. Agency Reports

    A. HRSA Drs. Marie Mann and Judy Hagopian and Ms. Shanese Baylor presented an update on current activities. It was noted that the Talent Bill might provide a number of opportunities should it be funded for the intended $10 million. HRSA would support efforts at increasing the frequency of meetings among the various agencies related to the hemoglobinopathies and the hemophilias as described above.

    B. Veterans Administration. Dr. Joseph DeSimone was interested in the suggestion that the VA consider a comprehensive approach to sickle cell disease in view of its being the one organization with the existing infrastructure that might be able to address the many issues involved. In the past, the VA has often served as a model for the approach to large populations.

  8. Dates of Next Meetings
  9. June 6, 2005

    November 7, 2005


    Theodore Wun, M.D.


    Sickle Cell Disease Advisory Committee


    Charles M. Peterson, M.D.

    Executive Secretary

    Sickle Cell Disease Advisory Committee

    Last updated: October 28, 2007

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