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Comparison of Cytokine Profiles in Aqueous Humor of Patients With Age Related Macular Degeneration (AMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03418220
Recruitment Status : Recruiting
First Posted : February 1, 2018
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:
Age-related macular degeneration (AMD) affects 2 million people in France. It characterized by progressive degeneration of the central area of the retina allowing detailed vision. It is the main cause of irreversible blindness in France. All patients initially present an early form, the latter can evolve in two different ways: the atrophic form, which progresses slowly, and the exudative or neovascular form, of more rapid evolution. While the treatment of exudative AMD has improved dramatically in recent years, there is currently no therapy for atrophic AMD. Recently, it has been demonstrated in atrophic AMD, an accumulation of inflammatory cells, macrophages, in the sub-retinal space. This space is located between the pigment epithelium (PE) and the photoreceptors. It is physiologically devoid of immune cells (immune privilege). Macrophages will secrete many pro-inflammatory molecules, such as cytokines. It has been shown in mouse models that some cytokines (IL-1beta, IL6 et TNFalpha) have a deleterious role on (PE) and photoreceptors. The identification of specific cytokines in the aqueous humor of patients with atrophic AMD would help to better understand this disease and consider potential targeted therapies. This study will be conducted in the ophthalmology department of the Croix-Rousse Hospital in Lyon. 80 patients will be recruited and divided into 4 groups: three experimental groups of 20 patients with : Early / Intermediate AMD, atrophic AMD or exudative AMD, and one control group of 20 patients without signs of AMD. Assays of the markers will be performed using the Luminex® technique on aqueous humor and blood samples collected for all patients during cataract surgery. The concentrations obtained in the aqueous humor will be normalized on their respective blood levels in order to confirm the intraocular secretion of these markers,. The identification of particular cytokine profiles in atrophic AMD compared to other forms of AMD would support emerging hypotheses of involvement of specific inflammatory cells in this pathology. There is currently no treatment available for atrophic AMD. If molecular screening identifies one or more specific biomarkers, targeted therapy may be considered.

Condition or disease Intervention/treatment Phase
Macular Degeneration, Age-Related Other: blood and aqueous humor sampling Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: Comparison of Cytokine Profiles in Aqueous Humor of Patients With Age Related Macular Degeneration (AMD)
Actual Study Start Date : November 22, 2017
Estimated Primary Completion Date : February 15, 2020
Estimated Study Completion Date : February 15, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
AMD early / intermediate
A blood and aqueous humor sample will be taken during cataract surgery in patients with AMD early / intermediate
Other: blood and aqueous humor sampling
The blood sample will be centrifuged. The plasma will be recovered. Plasma and aqueous humor will be frozen and stored at -80° Celsius. The search of 27 markers of inflammation will be performed by the kit LUMINEX Bio-rad (Bio-Rad, M500KCAF0Y).

AMD exudative
A blood and aqueous humor sample will be taken during cataract surgery in patients with AMD exudative
Other: blood and aqueous humor sampling
The blood sample will be centrifuged. The plasma will be recovered. Plasma and aqueous humor will be frozen and stored at -80° Celsius. The search of 27 markers of inflammation will be performed by the kit LUMINEX Bio-rad (Bio-Rad, M500KCAF0Y).

AMD atrophic
A blood and aqueous humor sample will be taken during cataract surgery in patients with AMD atrophic
Other: blood and aqueous humor sampling
The blood sample will be centrifuged. The plasma will be recovered. Plasma and aqueous humor will be frozen and stored at -80° Celsius. The search of 27 markers of inflammation will be performed by the kit LUMINEX Bio-rad (Bio-Rad, M500KCAF0Y).

control group
A blood and aqueous humor sample will be taken during cataract surgery in patients with cataract (control group)
Other: blood and aqueous humor sampling
The blood sample will be centrifuged. The plasma will be recovered. Plasma and aqueous humor will be frozen and stored at -80° Celsius. The search of 27 markers of inflammation will be performed by the kit LUMINEX Bio-rad (Bio-Rad, M500KCAF0Y).




Primary Outcome Measures :
  1. Comparison of concentrations of intraocular inflammation markers between the group of patients with atrophic AMD and the control group. [ Time Frame: day of surgery ]
    Aqueous humor sample will be collected during the cataract surgery in patient with atrophic AMD and in patient of control group. In order to identify and quantify intraocular inflammation markers in samples, LUMINEX® Multiplex analysis of the samples will be done by the Bio-Plex Pro Human Cytokine 27-Plex Panel (Bio-Rad, M500KCAF0Y). This test allow identification of one or more of the following 27 inflammation markers: basic FGF, Eotaxin, G-CSF, GM-CSF, interferon (IFNγ), interleukin (IL1β, IL1ra, IL2, IL4, IL5, IL6, IL7, IL8, IL9, IL10, IL12, IL13 , IL15, IL17), IP10, MCP1, MIP1α, MIP1β, PDGF-BB, RANTES, TNFα and Vascular Endothelial Growth Factor (VEGF).


Secondary Outcome Measures :
  1. Comparison of the concentration ratios of inflammation marker [aqueous humor / blood] between the group of patients with atrophic AMD and the control group. [ Time Frame: day of surgery ]

    Aqueous humor sample and the blood sample will be collected during the cataract surgery in patient with atrophic AMD and in patient of control group. In order to identify and quantify inflammation markers, LUMINEX® Multiplex analysis of the samples will be done by the Bio-Plex Pro Human Cytokine 27-Plex Panel (Bio-Rad, M500KCAF0Y).

    For each identified intraocular inflammatory marker, the ratio between the level of expression in the aqueous humor sample and the level of expression in the blood sample will be calculated.

    Each ratio will be compared between patients with atrophic AMD and patients of control group.


  2. Comparison of the concentration ratios of inflammation marker [aqueous humor / blood] between the different stages of AMD: early / intermediate, exudative or atrophic [ Time Frame: day of surgery ]

    Aqueous humor sample and the blood sample will be collected during the cataract surgery in patient with different stage of AMD : early / intermediate, exudative or atrophic.

    In order to identify and quantify inflammation markers, LUMINEX® Multiplex analysis of the samples will be done by the Bio-Plex Pro Human Cytokine 27-Plex Panel (Bio-Rad, M500KCAF0Y). For each identified intraocular inflammatory marker, the ratio between the level of expression in the aqueous humor sample and the level of expression in the blood sample will be calculated and compared between different stages of AMD: early / intermediate, exudative or atrophic.


  3. Comparison of the concentration ratios of inflammation marker [aqueous humor / blood] between the different types of atrophic AMD defined by autofluorescence exam (non-hyperautofluorescent or hyperautofluorescent form) [ Time Frame: day of surgery ]
    Autofluorescence exam allows in vivo mapping of lipofuscin distribution. Lipofuscin is a fluorophore of the retinal pigment epithelium. Autofluorescence represents in gray scale the spatial distribution of lipofuscin, and reflect the metabolic activity of the retinal pigment epithelium. Autofluorescence exam allows classification in different types of atrophic AMD. Autofluorescence exam was performed for all patients at the first visit. Aqueous humor sample and blood sample will be collected during the cataract surgery. In order to identify and quantify inflammation markers, LUMINEX® Multiplex analysis of the samples will be done by the Bio-Plex Pro Human Cytokine 27-Plex Panel (Bio-Rad, M500KCAF0Y). For each identified intraocular inflammatory marker, the ratio between the level of expression in the aqueous humor sample and the level of expression in the blood sample will be calculated, and compared between the different types of atrophic AMD.

  4. Comparison of the concentration ratios of inflammation marker [aqueous humor / blood] according to the macular atrophy area measured by autofluorescence in atrophic AMD. [ Time Frame: day of surgery ]
    Macular atrophy area is measured at first visit in autofluorescent exam. Aqueous humor sample and the blood sample will be collected during the cataract surgery. In order to identify and quantify inflammation markers, LUMINEX® Multiplex analysis of the samples will be done by the Bio-Plex Pro Human Cytokine 27-Plex Panel (Bio-Rad, M500KCAF0Y). For each identified intraocular inflammatory marker, the ratio between the level of expression in the aqueous humor sample and the level of expression in the blood sample will be calculated, and compared between the different size of macular atrophy area.

  5. Comparison of the concentration ratios of inflammation marker [aqueous humor / blood] according to the central retinal thickness measured by Optical Coherence Tomography (OCT) in atrophic AMD [ Time Frame: day of surgery ]
    OCT define precisely the retinal structures and their locations. Aqueous humor sample and the blood sample will be collected during the cataract surgery. In order to identify and quantify inflammation markers, LUMINEX® Multiplex analysis of the samples will be done by the Bio-Plex Pro Human Cytokine 27-Plex Panel (Bio-Rad, M500KCAF0Y). For each identified intraocular inflammatory marker, the ratio between the level of expression in the aqueous humor sample and the level of expression in the blood sample will be calculated, and compared between the different thickness of retina measured by OCT .

  6. Comparison of the concentration ratios of inflammation marker [aqueous humor / blood] according to the recognized risk factors of AMD [ Time Frame: day of surgery ]
    ratios of [aqueous humor / blood] concentrations of inflammation markers will be compared on age, female sex, smoking (number of pack-years), obesity (body mass index)



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • • GENERAL CRITERIA
  • Man or woman with age over 60 years,
  • Informed, written and signed consent by the patient and the investigator (no later than the day of inclusion) and before any investigation required by the research,
  • Patient affiliated with social security,
  • Patient willing and able to return to all clinical visits to the study and complete all related procedures.

    • SPECIFIC CRITERIA

  • Patient who need a cataract surgery,
  • Patient presenting in both eyes:

the same type of AMD defined according to the international AREDS study modified (Ferris et al., 2013) no other ophthalmological pathology (control group).

Exclusion Criteria:

  • • GENERAL CRITERIA
  • Major patient under tutorship or curatorship or unable to express consent,
  • Person deprived of liberty,
  • Patient participating in an ongoing clinical trial during the inclusion visit,

    • SPECIFIC CRITERIA

  • Patient with chronic ophthalmic pathologies other than cataract and AMD defined in the modified international AREDS study included in the eye (Ferris et al., 2013),
  • Patient who participated in a clinical trial of an experimental drug for atrophic AMD,
  • Patient taking systemically drugs with immunomodulatory action: immunosuppressants, immunomodulators, chemotherapy or corticosteroids,
  • Patient with systemic diseases modifying his immune status,
  • Patient with a history of diabetes,
  • Patient who received an anti-inflammatory eye treatment in both eyes in the 6 months preceding the surgery,
  • Patient having dynamic phototherapy on the included eye.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03418220


Contacts
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Contact: Thibaud MATHIS, MD 4 26 10 93 22 ext +33 thibaud.mathis@chu-lyon.fr
Contact: Christelle SZATANEK 4 26 73 27 24 ext +33 christelle.szatanek@chu-lyon.fr

Locations
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France
Hôpital de la Croix-Rousse Recruiting
Lyon, France, 69004
Contact: Thibaud Mathis, MD    4 26 10 93 22 ext +33    thibaud.mathis@chu-lyon.fr   
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
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Principal Investigator: Thibaud Mathis, MD Hospices Civils de Lyon
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT03418220    
Other Study ID Numbers: 69HCL17_0544
2017-A02365-48 ( Other Identifier: ANSM )
First Posted: February 1, 2018    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
Age related Macular Degeneration
Atrophy
Inflammation
Cytokines
test LUMINEX®
Additional relevant MeSH terms:
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Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases