Activation and Function of Eosinophils in Conditions With Blood or Tissue Eosinophilia
| Status: | Recruiting |
|---|---|
| Conditions: | Asthma, Infectious Disease, Neurology, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Immunology / Infectious Diseases, Neurology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 1 - 100 |
| Updated: | 3/27/2019 |
| Start Date: | April 4, 1994 |
| Contact: | Nicole C Holland-Thomas, R.N. |
| Email: | hollandnc@mail.nih.gov |
| Phone: | (301) 402-5969 |
Eosinophil Activation and Function in Parasitic Infections and Other Conditions With Increased Tissue or Peripheral Blood Eosinophilia in Humans
This study will investigate how, why and under what conditions eosinophils (a type of white
blood cell) become activated and will examine their function in immune reactions. Eosinophil
counts often rise in response to allergies, asthma, and parasitic worm infections. They can
also go up in uncommon autoimmune conditions and, rarely, in association with tumors.
Elevated levels of these cells is called eosinophilia. Usually, eosinophilia causes no
apparent symptoms, but in rare cases there may be local swelling and itching, allergic lung
problems, heart disease or nerve damage caused by the release of toxic substances in these
cells into body tissues.
Patients 1 to 100 years of age with eosinophil counts greater than 750/ml or an abnormal
accumulation of eosinophils in the skin or body tissues may be eligible for this study. All
participants will have a thorough medical history, physical examination and blood tests.
Depending on the person's age and symptoms, other diagnostic tests may be done, including
specialized studies of the eye, lungs, skin, bone marrow, nerves or heart. This is not a
treatment study, and no experimental treatments will be offered. Patients who require
treatment will receive standard medical care.
Certain other procedures may be requested solely for research purposes. All participants will
be asked to donate extra blood for laboratory studies investigating how immune cells and
other immune substances in the blood act to stimulate a rise in eosinophils. In addition,
some participants may undergo one or more of the following:
- Annual Follow-up evaluations - Physical examinations and blood tests to evaluate changes
in the patient's condition and eosinophil counts over time.
- Bone marrow biopsy and aspiration will be recommended during the initial evaluation, and
in certain patients at other times when it is important to look directly at the newly
developing cells in the bone marrow. For this procedure an area of skin and bone is
anesthetized with xylocaine (an anesthetic similar to that used by dentists), and a very
sharp needle is used to sample the bone marrow for evaluation. Bone marrow biopsy and
aspiration can have side effects of pain and/or bleeding into the skin and soft tissues
at the site of the procedure. Rarely the area at the biopsy site can become infected,
and is treated with antibiotics.
- Genetic testing: Some of the blood drawn from you as part of this study will be used for
genetic tests. Genetic tests can help researchers study how health or illness is passed
on to you by your parents or from you to your children. Any genetic information
collected or discovered about you or your family will be confidential.
- Leukapheresis (only patients 18 years and older) to collect large numbers of certain
cells - In this procedure, whole blood is collected through a needle placed in an arm
vein. The blood circulates through a machine that separates it into its components. The
white cells are then removed and the rest of the blood is returned to the body, either
through the same needle used to draw the blood or through a second needle placed in the
other arm.
blood cell) become activated and will examine their function in immune reactions. Eosinophil
counts often rise in response to allergies, asthma, and parasitic worm infections. They can
also go up in uncommon autoimmune conditions and, rarely, in association with tumors.
Elevated levels of these cells is called eosinophilia. Usually, eosinophilia causes no
apparent symptoms, but in rare cases there may be local swelling and itching, allergic lung
problems, heart disease or nerve damage caused by the release of toxic substances in these
cells into body tissues.
Patients 1 to 100 years of age with eosinophil counts greater than 750/ml or an abnormal
accumulation of eosinophils in the skin or body tissues may be eligible for this study. All
participants will have a thorough medical history, physical examination and blood tests.
Depending on the person's age and symptoms, other diagnostic tests may be done, including
specialized studies of the eye, lungs, skin, bone marrow, nerves or heart. This is not a
treatment study, and no experimental treatments will be offered. Patients who require
treatment will receive standard medical care.
Certain other procedures may be requested solely for research purposes. All participants will
be asked to donate extra blood for laboratory studies investigating how immune cells and
other immune substances in the blood act to stimulate a rise in eosinophils. In addition,
some participants may undergo one or more of the following:
- Annual Follow-up evaluations - Physical examinations and blood tests to evaluate changes
in the patient's condition and eosinophil counts over time.
- Bone marrow biopsy and aspiration will be recommended during the initial evaluation, and
in certain patients at other times when it is important to look directly at the newly
developing cells in the bone marrow. For this procedure an area of skin and bone is
anesthetized with xylocaine (an anesthetic similar to that used by dentists), and a very
sharp needle is used to sample the bone marrow for evaluation. Bone marrow biopsy and
aspiration can have side effects of pain and/or bleeding into the skin and soft tissues
at the site of the procedure. Rarely the area at the biopsy site can become infected,
and is treated with antibiotics.
- Genetic testing: Some of the blood drawn from you as part of this study will be used for
genetic tests. Genetic tests can help researchers study how health or illness is passed
on to you by your parents or from you to your children. Any genetic information
collected or discovered about you or your family will be confidential.
- Leukapheresis (only patients 18 years and older) to collect large numbers of certain
cells - In this procedure, whole blood is collected through a needle placed in an arm
vein. The blood circulates through a machine that separates it into its components. The
white cells are then removed and the rest of the blood is returned to the body, either
through the same needle used to draw the blood or through a second needle placed in the
other arm.
Subjects admitted on this protocol will have elevated eosinophil counts in the peripheral
blood or tissues or will be relatives of subjects with eosinophilia. Eosinophilic subjects
will undergo an extensive clinical evaluation focused on the identification of the cause of
eosinophilia and the presence of end organ manifestations. In addition, they will be
characterized in detail immunologically, and their blood cells and/or serum will be collected
to provide reagents (eg. specific antibodies, T-cell clones, etc.) that will be used in the
laboratory to address broader questions relating to the etiology of eosinophilia, its
immunoregulation, the degree and source of eosinophil activation, and/or the functional role
of eosinophils in the afferent arm of those immune response where they are prominent. While
the protocol is not primarily designed to study treatment of patients with blood and tissue
eosinophilia, the clinical and immunological responses to various medically indicated
therapies will be carefully monitored. The subjects themselves will be followed over time to
determine the kinetics and nature of the factors affecting their degree of eosinophilia and
the level of activation or degranulation of the eosinophils at various time points and in
response to various stimuli. It is anticipated that the subjects will receive a degree of
clinical evaluation, care and monitoring more extensive than that generally available and
that the specimens collected from them will prove to be valuable reagents for laboratory
studies related to eosinophilia, eosinophil activation and function. Recognized causes of
subjects hypereosinophilia will be treated appropriately either by our own clinical service
or by the referring physicians. Standard of care therapy may be provided when indicated for
HES variants. This protocol will also allow clinical and laboratory evaluation of family
members of subjects with eosinophilia in order to help identify genetic causes of
eosinophilia and to provide controls for immunologic studies. A subset of HES patients will
be interviewed and/or asked to fill out questionnaires to provide information about patient
signs and symptoms for use in the development of a patient-related outcomes questionnaire for
use in future treatment studies. Finally, adult subjects with gastrointestinal involvement
may be asked to provide stool samples for microbiome analysis and assessment of stool levels
of eosinophil granule proteins to explore the role of the microbiome in eosinophilic
gastrointestinal disease. Stool samples may also be obtained from adult subjects undergoing
endoscopy and/or colonoscopy as part of their initial evaluation and/or assessment of
response to treatment. Potential confounding variables, including body mass index, diet,
stool transit time and vitamin D levels will be assessed at the time of stool collection.
blood or tissues or will be relatives of subjects with eosinophilia. Eosinophilic subjects
will undergo an extensive clinical evaluation focused on the identification of the cause of
eosinophilia and the presence of end organ manifestations. In addition, they will be
characterized in detail immunologically, and their blood cells and/or serum will be collected
to provide reagents (eg. specific antibodies, T-cell clones, etc.) that will be used in the
laboratory to address broader questions relating to the etiology of eosinophilia, its
immunoregulation, the degree and source of eosinophil activation, and/or the functional role
of eosinophils in the afferent arm of those immune response where they are prominent. While
the protocol is not primarily designed to study treatment of patients with blood and tissue
eosinophilia, the clinical and immunological responses to various medically indicated
therapies will be carefully monitored. The subjects themselves will be followed over time to
determine the kinetics and nature of the factors affecting their degree of eosinophilia and
the level of activation or degranulation of the eosinophils at various time points and in
response to various stimuli. It is anticipated that the subjects will receive a degree of
clinical evaluation, care and monitoring more extensive than that generally available and
that the specimens collected from them will prove to be valuable reagents for laboratory
studies related to eosinophilia, eosinophil activation and function. Recognized causes of
subjects hypereosinophilia will be treated appropriately either by our own clinical service
or by the referring physicians. Standard of care therapy may be provided when indicated for
HES variants. This protocol will also allow clinical and laboratory evaluation of family
members of subjects with eosinophilia in order to help identify genetic causes of
eosinophilia and to provide controls for immunologic studies. A subset of HES patients will
be interviewed and/or asked to fill out questionnaires to provide information about patient
signs and symptoms for use in the development of a patient-related outcomes questionnaire for
use in future treatment studies. Finally, adult subjects with gastrointestinal involvement
may be asked to provide stool samples for microbiome analysis and assessment of stool levels
of eosinophil granule proteins to explore the role of the microbiome in eosinophilic
gastrointestinal disease. Stool samples may also be obtained from adult subjects undergoing
endoscopy and/or colonoscopy as part of their initial evaluation and/or assessment of
response to treatment. Potential confounding variables, including body mass index, diet,
stool transit time and vitamin D levels will be assessed at the time of stool collection.
- INCLUSION CRITERIA (Eosinophilic Subjects):
1. 1-100 years of age
2. documented peripheral blood eosinophil count >1500/mm^3, tissue eosinophilia
(abnormal accumulation of eosinophils in the skin or other body tissues) or
suspected eosinophilic end organ involvement
3. has a primary (non-NIH) physician for routine medical care
EXCLUSION CRITERIA (Eosinophilic Subjects):
1) medical conditions or therapies that the investigator feels put the subject at
unacceptable risk for participation in the study
INCLUSION CRITERIA (Relatives):
1. 1-100 years of age
2. extended family member of a study participant in 94-I-0079
EXCLUSION CRITERIA (Relatives):
1) any condition that the investigator feels put the subject at unacceptable risk for
participation in the study.
Participation of Women:
Women who are pregnant or breastfeeding will not be excluded, although procedures will be
limited to those that are clinically indicated and/or pose no increased risk during
pregnancy (such as echocardiopgraphy). Research blood collection will be limited in
participants who are pregnant or breastfeeding.
INCLUSION CRITERIA (Hypereosinophilic Syndrome (HES) Concept Elicitation Substudy):
Each participant must meet the following criteria to be enrolled in the study:
1. Diagnosis of HES for at least 6 months
2. Documentation of symptoms for a minimum of 12 months
3. A change in symptoms that required a change in medication at least once in the past 12
months
4. Age 12 years or older
5. Adequate written and oral fluency in English
6. Willing to provide written informed consent
7. Willing to have the interview audio-recorded
EXCLUSION CRITERIA (Hypereosinophilic Syndrome (HES) Concept Elicitation Substudy):
The presence of any of the following will exclude a subject from the study:
1. Has a cognitive or physical impairment that would interfere with the subject s ability
to complete the study.
2. Lack of fluency in spoken English
3. Positive for the FIP1L1-PDGFRA fusion tyrosine kinase gene translocation.
INCLUSION CRITERIA (Development of the Hypereosinophilic Syndrome Symptom Inventory
(HES-SI)):
1. Have an existing diagnosis of HES
2. Be enrolled on protocol 94-I-0079
3. Age 12 or greater
4. Written and oral fluency in English
5. Willingness to provide informed consent
EXCLUSION CRITERIA (Development of the Hypereosinophilic Syndrome Symptom Inventory
(HES-SI)):
Any condition that, in the investigator s opinion, places the subject at undue risk by
participating in the study
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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