NeutropeniaNCT00059423
Natural History Study for BEN
An observational study of Neutropenia and Agranulocytosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 5 to 99 years
- Conditions the study is for
- Neutropenia, Agranulocytosis, Hematologic Diseases
- How many people
- 178 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jun 2003to 26 Jun 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Since BEN is a condition of individuals of African descent, volunteer recruitment will be focused in this ethnic population. Accrual for BEN subjects will be based on entry criteria, and not on gender or age (in those 5 years or greater). The minimum age is 5 years because these older children would have larger veins and would be more likely to cooperate with blood draws. Subjects without BEN will be selected to match age and gender of BEN subjects to minimize the differential effects of age and gender to the responses to G-CSF and dexamethasone and in microarray analyses.
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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:
Read more
- 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.
Read the 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 purpose 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.
- Keywords
- Leukapheresis, G-CSF, Dexamethasone, mRNA, Benign Ethnic Neutropenia, BEN, Healthy Volunteer, HV
- Medical subject headings
- Neutropenia, Agranulocytosis, Hematologic Diseases, Leukocyte Disorders, Leukopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Individuals of African descent with benign ethnic neutropenia (BEN) at baseline | |
| 2 | Individuals of African descent without benign ethnic neutropenia (BEN) at baseline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serial blood counts in BEN
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).
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2003 (estimated)
- Study start3 Jun 2003
- Primary completion23 Apr 2019
- Study completion26 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for NeutropeniaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 178 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Matthew M Hsieh, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00059423
- Sponsor's protocol ID
- 030168
- Other IDs
- 03-H-0168
- Status last verified
- Jun 2020
- First submitted
- 25 Apr 2003
- Last updated
- 22 Mar 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 3518419Haddy 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.
PubMed 10385477Mason 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.
PubMed 463924
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History and Molecular Characterization of Benign Ethnic Neutropenia in Individuals of African Descent
- ClinicalTrials.gov ID
- NCT00059423
- Acronym / sponsor ID
- 030168
- Keywords
- Leukapheresis, G-CSF, Dexamethasone, mRNA, Benign Ethnic Neutropenia, BEN, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 178 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 3 Jun 2003 (actual)
- Primary completion
- 23 Apr 2019 (actual)
- Study completion
- 26 Jun 2020 (actual)
- First posted
- 25 Apr 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 purpose 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Individuals of African descent with benign ethnic neutropenia (BEN) at baseline |
| 2 | – | –Individuals of African descent without benign ethnic neutropenia (BEN) at baseline |
Who may qualify
- Ages
- 5 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Since BEN is a condition of individuals of African descent, volunteer recruitment will be focused in this ethnic population. Accrual for BEN subjects will be based on entry criteria, and not on gender or age (in those 5 years or greater). The minimum age is 5 years because these older children would have larger veins and would be more likely to cooperate with blood draws. Subjects without BEN will be selected to match age and gender of BEN subjects to minimize the differential effects of age and gender to the responses to G-CSF and dexamethasone and in microarray analyses.
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Serial blood counts in BEN
Time frame: Ongoing
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
- Background: PubMed 3518419Ash 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.
- Background: PubMed 10385477Haddy 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.
- Background: PubMed 463924Mason 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew M Hsieh, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neutropenia and Agranulocytosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serial blood counts in BEN (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00059423, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2024.