Gene Message (mRNA) Analysis of Granulocytes - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00059423

Purpose

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.

Condition
Neutropenia

Study Type:	Observational
Official Title:	Natural History and Molecular Characterization of Benign Ethnic Neutropenia in Individuals of African Descent

Resource links provided by NLM:

Genetics Home Reference related topics: cyclic neutropenia Help Me Understand Genetics

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:	99999999
Study Start Date:	April 2003

Detailed Description:

Benign ethnic neutropenia (BEN) is defined by peripheral blood absolute neutrophil count less than 1.5 x 10 (9) per liter without an increase in infections. This condition has been described in individuals of African descent. Although these individuals have normal myeloid maturation on bone marrow examinations, they appear to release fewer neutrophils into the circulation when stimulated by hydrocortisone, compared to normal controls. This suggests that there may be differences in the regulation of neutrophil release or trafficking. In the past decade, granulocyte-colony stimulating factor (G-CSF) has been widely used in a variety of clinical settings, from patients with chemotherapy-induced neutropenia to normal volunteers for peripheral blood stem cell collection. G-CSF, however, has not been used in individuals with BEN. Furthermore, gene expression in neutrophil proliferation and trafficking has not been studied in these individuals. The purposes of this study are to (1) identify individuals with BEN; (2) follow the natural history of BEN; (3) determine if there is a familial inheritance pattern; (4) characterize and compare neutrophil response to dexamethasone and G-CSF; (5) compare the pattern of neutrophil gene expression by microarray analyses; and (6) determine if mutations are present at the DNA level to account for gene expression pattern differences in individuals of African descent with and without BEN at baseline, post dexamethasone, and post G-CSF stimulation.

Eligibility

Ages Eligible for Study:	5 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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 >=1,500/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, in the last 6 months, with granulocytes < 1,500/mm3, platelet > 150,000/mm3, hemoglobin > 12.5g/dL, and normal MCV
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

4.2.4 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00059423

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892
Sub-Investigator: Patient Recruitment and Public Liaison Office (PRPL) For more information at the NIH Clinical Center contact

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

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.

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. Review.

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.

ClinicalTrials.gov Identifier:	NCT00059423 History of Changes
Other Study ID Numbers:	030168, 03-H-0168
Study First Received:	April 25, 2003
Last Updated:	January 21, 2012
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Leukapheresis
G-CSF
Dexamethasone
mRNA

Benign Ethnic Neutropenia
BEN
Healthy Volunteer
HV

Additional relevant MeSH terms:

Neutropenia
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases

ClinicalTrials.gov processed this record on February 09, 2012