Gene Message (mRNA) Analysis of Granulocytes

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00059423
First received: April 25, 2003
Last updated: March 14, 2014
Last verified: January 2014
  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:

  1. identify individuals of African descent with BEN.
  2. determine the effects of two drugs, G-CSF and dexamethasone, on granulocyte production and movement.
  3. 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:


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 (Bullet)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< TAB> 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Matthew M Hsieh, M.D. (301) 402-7687 matthewhs@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Matthew M Hsieh, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00059423     History of Changes
Other Study ID Numbers: 030168, 03-H-0168
Study First Received: April 25, 2003
Last Updated: March 14, 2014
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 July 22, 2014