- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00059423
Natural History Study for BEN
Natural History and Molecular Characterization of Benign Ethnic Neutropenia in Individuals of African Descent
In recent decades, hematologists have noticed that persons of African descent sometimes have lower white blood cell counts of a certain type, called granulocytes. These cells help to fight infections. The lower number of granulocytes in this situation does not appear to lead to more infections, and these individuals do not have any symptoms. This condition is called benign ethnic neutropenia (BEN), and is observed in a small percentage of individuals of African descent. This study will investigate the condition by studying people with and without BEN.
The goals of this study are to:
- identify individuals of African descent with BEN.
- determine the effects of two drugs, G-CSF and dexamethasone, on granulocyte production and movement.
- determine whether there are differences in those with and without BEN in the way genes are stimulated after the administration of G-CSF and dexamethasone.
Study participants will be asked to interview with the research team, undergo physical exams, donate a blood sample, and receive G-CSF by injection, followed by dexamethasone (orally) about three weeks later. They also will be required to undergo apheresis three times, a procedure in which blood is drawn from a donor and separated into its components. Some components are retained for research analyses, such as granulocytes, and small amount of blood; the remainder is returned by transfusion to the donor. This procedure will be required of participants before they receive G-CSF, the day after they receive G-CSF, and the day after they receive dexamethasone. Gene messages (mRNA will be isolated from granulocytes, and analyzed to better understand granulocyte growth and movement.
Study Overview
Status
Detailed Description
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
- INCLUSION CRITERIA:
- Individuals of African descent of age 5 or greater
- Normal renal function: creatinine <1.5 mg/dL and proteinuria <1+
- Normal liver function: bilirubin <1.5 mg/dL and transaminases within normal limits
- For control subjects: WBC within normal range (3,300-9,600/mm3), granulocytes/neutrophils greater than or equal to 2,000/mm3, platelets >150,000/mm3, hemoglobin > 11.5g/dL and normal MCV
- For benign ethnic neutropenic subjects: two blood counts, at least 1 month apart, with granulocytes/neutrophils <1,500/mm3, platelet >150,000/mm3, hemoglobin >12.5g/dL, and normal MCV. We will also follow subjects whose neutrophil counts are between 1500 and 2000/mm3 in a separate cohort periodically (e.g. once every 1-2 years) to see if their blood counts behave more like BEN or normal subjects.
- Female volunteers of childbearing age should not be pregnant
- Meets NIH Department of Transfusion Medicine (DTM) eligibility criteria for blood component donation for in vitro research uses (negative serologic tests for syphilis, hepatitis B and C, HIV, and HTLV-1)
- Ability to give informed consent to participate in the protocol
EXCLUSION CRITERIA:
- Any underlying hematologic disorder including anemia, and sickle cell disease. Subjects with thalassemia or sickle cell trait are not excluded.
- Current use of corticosteroids, e.g. prednisone, dexamethasone, or hydrocortisone. Corticosteroids must be discontinued at least one month prior
- Active or chronic viral, bacterial, fungal, or parasitic infection. Any antibiotic use should be discontinued at least one month prior
- History of autoimmune disease, such as rheumatoid arthritis or systemic lupus erythematosus, or positive anti-nuclear antibody (ANA ELISA) of 3 E.U. (ELISA units) or greater.
- Low B12 or folate levels, or abnormal thyroid function tests
- History of cancer or chemotherapy, except squamous carcinoma of the skin and cervical carcinoma in situ
- Pregnant woman or positive urine pregnancy test
- History of clinically significant cardiovascular disease (cardiology consultation may be obtained when clinically indicated)
- Any positive serum screening test as listed below
- Allergy to G-CSF or bacterial E. coli products
- Active pulmonary disease or a pulse-ox level of less than 95% on screening exam
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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1
Individuals of African descent with benign ethnic neutropenia (BEN) at baseline
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2
Individuals of African descent without benign ethnic neutropenia (BEN) at baseline
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serial blood counts in BEN
Time Frame: Ongoing
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In our study, we hope to further elucidate the etiology of BEN in research subjects by isolating granulocyte mRNA after G-CSF and dexamethasone stimulation, applying microarray analyses to screen for gene expression differences, and confirming expression pattern differences by DNA analyses.
We will focus on genes that are important in the proliferation and trafficking of neutrophils,such as PRV-1, elastase, myeloblastin, transcription factor PU.1, CAAT enhancing binding protein-alpha (C /EBP), stromal derived factor-1 (SDF-1), and CXC receptor-4 (CXCR4).
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Ongoing
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Collaborators and Investigators
Investigators
- Principal Investigator: Matthew M Hsieh, M.D., National Heart, Lung, and Blood Institute (NHLBI)
Publications and helpful links
General Publications
- Ash RC, Mendelsohn LA, Marshall ME. Hemopoietic marrow function in chronic neutropenia of blacks: cure of aplastic anemia by allogeneic marrow transplantation from a neutropenic sibling donor. Am J Hematol. 1986 Jun;22(2):205-12. doi: 10.1002/ajh.2830220212.
- Haddy TB, Rana SR, Castro O. Benign ethnic neutropenia: what is a normal absolute neutrophil count? J Lab Clin Med. 1999 Jan;133(1):15-22. doi: 10.1053/lc.1999.v133.a94931.
- Mason BA, Lessin L, Schechter GP. Marrow granulocyte reserves in black Americans. Hydrocortisone-induced granulocytosis in the "benign" neutropenia of the black. Am J Med. 1979 Aug;67(2):201-5. doi: 10.1016/0002-9343(79)90391-7.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 030168
- 03-H-0168
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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