Ignite Creation Date:
2024-05-05 @ 5:02 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00379275
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2006-09-20
Brief Title:
Eye and Immunogenetic Features of Sarcoidosis
Sponsor:
National Eye Institute NEI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Ocular and Immuno-Genetic Manifestations of Sarcoidosis
Status:
COMPLETED
Status Verified Date:
2007-12-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate patients with sarcoidosis to understand how the disease affects the body Sarcoidosis is a disease that results from inflammation of body tissues The lungs lymph nodes in the chest skin and eyes are most commonly affected As the disease progresses small lumps or granulomas appear in the affected tissues In most cases the granulomas clear up but in cases where they do not heal and disappear the tissues tend to remain inflamed Eye inflammation uveitis associated with sarcoidosis can cause various eye diseases sometimes leading to blindness This study will examine the clinical immunological and genetic features of ocular sarcoidosis
Patients 6 years of age and older with sarcoidosis may be eligible for this study Candidates are screened with the following procedures
Completion of a questionnaire with medical social and demographic information
Blood draw for laboratory tests
Complete eye examination including measurement of eye pressure and dilation of the pupils to examine the back of the eye Fluorescein angiography may be done This test involves injecting a dye into a vein in the arm The dye travels to the blood vessels in the eyes A camera flashes a blue light into the eye and takes pictures of the retina that show whether the dye has leaked from the blood vessels into the retina Other photographs of the eye may also be taken using a special camera
Participants are followed in conjunction with their local eye doctor as required by the status of their disease Patients whose disease is stable are seen for an initial examination and followed every 12 months for 3 years
Patients 6 years of age and older with sarcoidosis may be eligible for this study Candidates are screened with the following procedures
Completion of a questionnaire with medical social and demographic information
Blood draw for laboratory tests
Complete eye examination including measurement of eye pressure and dilation of the pupils to examine the back of the eye Fluorescein angiography may be done This test involves injecting a dye into a vein in the arm The dye travels to the blood vessels in the eyes A camera flashes a blue light into the eye and takes pictures of the retina that show whether the dye has leaked from the blood vessels into the retina Other photographs of the eye may also be taken using a special camera
Participants are followed in conjunction with their local eye doctor as required by the status of their disease Patients whose disease is stable are seen for an initial examination and followed every 12 months for 3 years
Detailed Description:
BACKGROUND
Sarcoidosis is a multi-systemic granulomatous disease The lungs thoracic lymph nodes the skin and the eyes are the most commonly affected organs Most patients with sarcoidosis present with respiratory symptoms Sarcoid uveitis is usually suspected when ocular inflammation is found in conjunction with suggestive serological and radiological studies Currently the diagnosis of sarcoidosis requires the demonstration of non-caseating granulomas on biopsy but even this is not always diagnostic more sensitive and specific noninvasive tools are needed
Ophthalmic involvement has been reported in as many as 40 of patients with sarcoidosis but most series report ophthalmic findings in approximately 25 of patients who develop chronic systemic sarcoidosis Uveitis associated with sarcoidosis can be very diverse including acute non-granulomatous or chronic granulomatous iridocyclitis vitritis retinal vasculitis choroiditis with choroidal granulomas and papillitis secondary to optic nerve granulomas and it can cause ocular morbidity due to a high incidence of glaucoma and cataracts Other ophthalmic findings include lacrimal gland enlargement secondary Sjogrens disease scleritis orbital gland involvement secondary proliferative retinopathy subretinal neovascularization and optic neuropathy
To better evaluate and diagnose patients we also need to improve our ability to predict susceptibility and prognosis especially among African-Americans Current epidemiologic studies of sarcoidosis indicate that in the United States African Americans have about a threefold higher age-adjusted annual incidence 355100000 compared with Caucasians 109100000 In addition African Americans with chronic sarcoidosis are more likely to develop ocular manifestations than whites The study of ocular sarcoidosis is important because it is a leading inflammatory cause of blindness and ocular morbidity In large surveys of patients with uveitis approximately 5 of patients were found to have ocular sarcoidosis and approximately 10 of these patients become blind in at least one eye
AIMS
AIM 1 CLINICAL ANALYSIS
Documentation of
1 Clinical features of sarcoidosis associated uveitis
2 Chronological association of ocular disease to histopathologic diagnosis of sarcoidos
3 Family history of sarcoidosis
4 Previous therapies and response
5 Ocular status compared with systemic disease status current and historical Environmental exposure history
AIM 2 IMMUNOLOGICAL ANALYSIS
One of the goals of this study is to determine the diagnostically important cytokines in biopsy-proven ocular sarcoidosis
The chemokine profile of the Peripheral Blood Mononuclear Cells and Broncho-Alveolar Lavage Fluid BALF of pulmonary sarcoidosis patients has been reported and many cytokines have been implicated in the pathogenesis of this disease
1 Serum Level for
A TNF alpha
B MIP-1 alpha
C IL-8
D IL-2
E TGF Beta
F INF gamma
2 Immunophenotyping of whole blood cells and BALF by flow cytometry
Focus on
A T cell sub-typing examples CD4 CD8
B NK cell sub-typing examplesCD56 KIR
3 TLRs sub-typing
AIM 3 GENETIC ANALYSIS
Serum analysis for HLA Class I and II typing
A cohort of 100 patients with biopsy-proven sarcoidosis will be recruited from the Uveitis and Ocular Immunology Clinic at the National Eye Institute and the Pulmonary Clinic at the National Heart Lung and Blood Institute
FUTURE AIMS
We aim to characterize the TLR activation profile in patients with ocular sarcoidosis and compare them to patients with pulmonary sarcoidosis and normal volunteers Using this immuno-genetic classification scheme in conjunction with HLA typing we hope to develop novel diagnostic andor prognostic criteria for sarcoidosis In addition the TLR activation profile may allow risk stratification for different sarcoidosis phenotypes
METHODS
A cohort of 100 patients with biopsy-proven sarcoidosis will be recruited from the Uveitis and Ocular Immunology Clinic at the National Eye Institute and the Pulmonary Clinic at the National Heart Lung and Blood Institute After obtaining informed consent the patients will be invited to participate in the study After appropriate enrollment they will undergo the following
1 Completion of a questionnaire with medical social and demographic data
2 A complete ophthalmologic examination
3 Baseline serologic analysis
4 Baseline serum analysis for immunologic analysis
5 HLA-Typing
6 Patients who are quiescent will be seen at baseline with a second visit at 1 year
7 Patients who are active will be treated appropriately by their referring ophthalmologist or on a treatment protocol at the National Eye Institute
Sarcoidosis is a multi-systemic granulomatous disease The lungs thoracic lymph nodes the skin and the eyes are the most commonly affected organs Most patients with sarcoidosis present with respiratory symptoms Sarcoid uveitis is usually suspected when ocular inflammation is found in conjunction with suggestive serological and radiological studies Currently the diagnosis of sarcoidosis requires the demonstration of non-caseating granulomas on biopsy but even this is not always diagnostic more sensitive and specific noninvasive tools are needed
Ophthalmic involvement has been reported in as many as 40 of patients with sarcoidosis but most series report ophthalmic findings in approximately 25 of patients who develop chronic systemic sarcoidosis Uveitis associated with sarcoidosis can be very diverse including acute non-granulomatous or chronic granulomatous iridocyclitis vitritis retinal vasculitis choroiditis with choroidal granulomas and papillitis secondary to optic nerve granulomas and it can cause ocular morbidity due to a high incidence of glaucoma and cataracts Other ophthalmic findings include lacrimal gland enlargement secondary Sjogrens disease scleritis orbital gland involvement secondary proliferative retinopathy subretinal neovascularization and optic neuropathy
To better evaluate and diagnose patients we also need to improve our ability to predict susceptibility and prognosis especially among African-Americans Current epidemiologic studies of sarcoidosis indicate that in the United States African Americans have about a threefold higher age-adjusted annual incidence 355100000 compared with Caucasians 109100000 In addition African Americans with chronic sarcoidosis are more likely to develop ocular manifestations than whites The study of ocular sarcoidosis is important because it is a leading inflammatory cause of blindness and ocular morbidity In large surveys of patients with uveitis approximately 5 of patients were found to have ocular sarcoidosis and approximately 10 of these patients become blind in at least one eye
AIMS
AIM 1 CLINICAL ANALYSIS
Documentation of
1 Clinical features of sarcoidosis associated uveitis
2 Chronological association of ocular disease to histopathologic diagnosis of sarcoidos
3 Family history of sarcoidosis
4 Previous therapies and response
5 Ocular status compared with systemic disease status current and historical Environmental exposure history
AIM 2 IMMUNOLOGICAL ANALYSIS
One of the goals of this study is to determine the diagnostically important cytokines in biopsy-proven ocular sarcoidosis
The chemokine profile of the Peripheral Blood Mononuclear Cells and Broncho-Alveolar Lavage Fluid BALF of pulmonary sarcoidosis patients has been reported and many cytokines have been implicated in the pathogenesis of this disease
1 Serum Level for
A TNF alpha
B MIP-1 alpha
C IL-8
D IL-2
E TGF Beta
F INF gamma
2 Immunophenotyping of whole blood cells and BALF by flow cytometry
Focus on
A T cell sub-typing examples CD4 CD8
B NK cell sub-typing examplesCD56 KIR
3 TLRs sub-typing
AIM 3 GENETIC ANALYSIS
Serum analysis for HLA Class I and II typing
A cohort of 100 patients with biopsy-proven sarcoidosis will be recruited from the Uveitis and Ocular Immunology Clinic at the National Eye Institute and the Pulmonary Clinic at the National Heart Lung and Blood Institute
FUTURE AIMS
We aim to characterize the TLR activation profile in patients with ocular sarcoidosis and compare them to patients with pulmonary sarcoidosis and normal volunteers Using this immuno-genetic classification scheme in conjunction with HLA typing we hope to develop novel diagnostic andor prognostic criteria for sarcoidosis In addition the TLR activation profile may allow risk stratification for different sarcoidosis phenotypes
METHODS
A cohort of 100 patients with biopsy-proven sarcoidosis will be recruited from the Uveitis and Ocular Immunology Clinic at the National Eye Institute and the Pulmonary Clinic at the National Heart Lung and Blood Institute After obtaining informed consent the patients will be invited to participate in the study After appropriate enrollment they will undergo the following
1 Completion of a questionnaire with medical social and demographic data
2 A complete ophthalmologic examination
3 Baseline serologic analysis
4 Baseline serum analysis for immunologic analysis
5 HLA-Typing
6 Patients who are quiescent will be seen at baseline with a second visit at 1 year
7 Patients who are active will be treated appropriately by their referring ophthalmologist or on a treatment protocol at the National Eye Institute
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-EI-0239 | None | None | None |