Natural History of Sickle Cell Disease

• ClinicalTrials.gov Identifier: NCT00081523
• Recruitment Status: Recruiting
• First Posted: April 15, 2004
• Last Update Posted: March 27, 2023
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Tracking Information

• First Submitted Date: April 15, 2004
• First Posted Date: April 15, 2004
• Last Update Posted Date: March 27, 2023
• Actual Study Start Date: April 29, 2004
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: October 6, 2021)

To gather, through clinical experience, information regarding the natural history, co-morbid conditions and outcomes, and complications relating to sickle cell disease and other hemolytic disorders in minority/ethnic patients [ Time Frame: ongoing ]

Better characterization of the natural history of sickle cell disease

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Natural History of Sickle Cell Disease
• Official Title: Studies of the Natural History of Sickle Cell Disease
• Brief Summary: This study is not a treatment protocol and no experimental treatments are involved. Study participants may be seen as needed for clinical, translational and basic research studies, or as medically indicated. Subjects will receive their general medical care outside the NIH and will be seen at our clinic or at CNHS with varying frequency. Subjects may be seen for multiple visits. Subjects may be asked to return for additional testing as needed. Clinical care for patients with sickle cell disease will be provided as appropriate through the Sickle Cell Clinic and the inpatient clinical center.

Detailed Description

This protocol will permit the establishment of a repository of biospecimens from individuals affected with sickle cell disease to identify and evaluate underlying disease mechanism(s), and to facilitate understanding of the pathogenesis and natural history of vaso-occlusive painful crisis and other complications of the disease. Patients will be evaluated with a medical history and physical examination and routine laboratory studies will be obtained as needed to assess diagnosis, disease activity, and disease complications and to monitor for treatment-related responses and toxicities. This protocol may also provide for the continued storage and analysis of clinical and research data, and biospecimens previously obtained from other NIH Institutional Review Board (IRB)-approved protocols with subject consent.

Patients eligible for other research protocols will be offered an opportunity to participate in these studies after signed informed consent has been obtained. Apart from such protocols, any medical care or additional tests/investigations recommended or provided to the patient will be consistent with routine standards of practice and will be provided in consultation with the patient s referring physician.

• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: The study will be open to all eligible subjects based on inclusion and exclusion criteria and who provide informed consent. Patients may self-refer, be recruited through the NIH office of recruitment, and may include patients participating on other NIH IRB approved protocols. The study will also be open to all eligible pediatric patients receiving medical care for SCD at Children s National.
• Condition: Pain Crisis
• Intervention: Not Provided

Study Groups/Cohorts

Patients

Individuals with known or suspected sickle cell disease

Publications *

• Tumburu L, Ghosh-Choudhary S, Seifuddin FT, Barbu EA, Yang S, Ahmad MM, Wilkins LHW, Tunc I, Sivakumar I, Nichols JS, Dagur PK, Yang S, Almeida LEF, Quezado ZMN, Combs CA, Lindberg E, Bleck CKE, Zhu J, Shet AS, Chung JH, Pirooznia M, Thein SL. Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease. Blood. 2021 Jun 3;137(22):3116-3126. doi: 10.1182/blood.2020009063. Erratum In: Blood. 2022 Sep 15;140(11):1327.
• Giudice V, Feng X, Lin Z, Hu W, Zhang F, Qiao W, Ibanez MDPF, Rios O, Young NS. Deep sequencing and flow cytometric characterization of expanded effector memory CD8+CD57+ T cells frequently reveals T-cell receptor Vbeta oligoclonality and CDR3 homology in acquired aplastic anemia. Haematologica. 2018 May;103(5):759-769. doi: 10.3324/haematol.2017.176701. Epub 2018 Feb 1.
• Nguyen KL, Tian X, Alam S, Mehari A, Leung SW, Seamon C, Allen D, Minniti CP, Sachdev V, Arai AE, Kato GJ. Elevated transpulmonary gradient and cardiac magnetic resonance-derived right ventricular remodeling predict poor outcomes in sickle cell disease. Haematologica. 2016 Feb;101(2):e40-3. doi: 10.3324/haematol.2015.125229. Epub 2015 Nov 20. No abstract available.
• Wang X, Mendelsohn L, Rogers H, Leitman S, Raghavachari N, Yang Y, Yau YY, Tallack M, Perkins A, Taylor JG 6th, Noguchi CT, Kato GJ. Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Kruppel-like factor. Blood. 2014 Aug 7;124(6):946-54. doi: 10.1182/blood-2013-11-539718. Epub 2014 Jun 10.
• Koh C, Turner T, Zhao X, Minniti CP, Feld JJ, Simpson J, Demino M, Conrey AK, Jackson MJ, Seamon C, Kleiner DE, Kato GJ, Heller T. Liver stiffness increases acutely during sickle cell vaso-occlusive crisis. Am J Hematol. 2013 Nov;88(11):E250-4. doi: 10.1002/ajh.23532. Epub 2013 Aug 1.
• Tumblin A, Tailor A, Hoehn GT, Mack AK, Mendelsohn L, Freeman L, Xu X, Remaley AT, Munson PJ, Suffredini AF, Kato GJ. Apolipoprotein A-I and serum amyloid A plasma levels are biomarkers of acute painful episodes in patients with sickle cell disease. Haematologica. 2010 Sep;95(9):1467-72. doi: 10.3324/haematol.2009.018044. Epub 2010 Apr 7.
• Olnes M, Chi A, Haney C, May R, Minniti C, Taylor J 6th, Kato GJ. Improvement in hemolysis and pulmonary arterial systolic pressure in adult patients with sickle cell disease during treatment with hydroxyurea. Am J Hematol. 2009 Aug;84(8):530-32. doi: 10.1002/ajh.21446.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 7, 2020): 3500
• Original Enrollment (submitted: June 23, 2005): 9999999
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

Eligibility Criteria

• INCLUSION CRITERIA:
• Individuals with known or suspected sickle cell disease
• 2 years of age and older
• Willing to provide informed consent or appropriate informed consent from parent or legal guardian
• Patients seen at sickle outpatient clinics at any one of the participating centers (CNHS or NIH).

EXCLUSION CRITERIA:

• Patient and/or guardian unable and unwilling to give informed consent or assent.
• Patients less than 2 years of age.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Mai Hill, R.N.; (301) 402-2105; mai.hill@nih.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00081523
• Other Study ID Numbers: 040161; 04-H-0161
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: .The team is in the process of making a determination.

• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Swee Lay Thein, M.D.; National Heart, Lung, and Blood Institute (NHLBI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: March 15, 2023