Survival of Monocytes Collected From Patients With Atrophic AMD in Retinal Pigmented Epithelium Explants

NCT ID: NCT04697095

Last Updated: 2025-03-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-01
• Study Completion Date: 2025-12-02

Brief Summary

Age-related macular degeneration (AMD) affects 2 million people in France and is the main cause of irreversible blindness in France. All patients initially have an early form of the disease. This early form can evolve in two different ways: the atrophic form, which progresses slowly, and the exudative or neovascular form, which has a more rapid evolution. While there are treatments for the exudative form of the disease, there is currently no therapy for the atrophic form of AMD. Recently, it has been demonstrated in atrophic AMD that there is accumulation of inflammatory cells, monocytes, in the sub-retinal space. This space is located between the retinal pigment epithelium (RPE) and photoreceptors. It is physiologically devoid of immune cells (immune privilege). Monocytes secrete many pro-inflammatory molecules, such as cytokines. Some cytokines (IL-1, IL6 and TNF) have a deleterious role on RPE and photoreceptors in mouse models. The identification of specific cytokines would help to better understand this disease and consider potential targeted therapies. Our project is based on the hypothesis that monocytes extracted from patients with AMD have a superior survival on RPE compared to monocytes extracted from healthy patients (without retinal pathology), and more particularly in atrophic forms of AMD. The main aim of this study is to compare the survival of monocytes extracted from patients with atrophic AMD to monocytes extracted from patients without retinal pathology (control) on retinal pigment epithelial cell lines (ARPE-19). Survival will be evaluated by automated counting of monocytes after 24 hours of culture on ARPE-19 after specific immunostaining of monocytes. If the survival of monocytes from patients with the late form of AMD is increased then therapy directly targeting this pathological accumulation of monocytes could be considered. Moreover, the identification of increased secretion of certain cytokines and the demonstration of their deleterious effect on retinal physiology could lead to targeted therapies against them.

Conditions

Age Related Macular Degeneration

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

early / intermediate AMD without neovessels and without macular atrophy

Group Type: EXPERIMENTAL

Blood samples

Intervention Type: OTHER

: The blood sample from all groups will be taken on the day of inclusion, in the ophthalmology department. The patient will be cared for by a nurse and then taken to the collection room. A 100 ml sample will be taken (10 tubes of 10 ml). Blood samples will be labeled with the patient's identification number as part of the protocol. They will be transported to the research laboratory in order to be picked up for monocyte extraction. The purification of blood monocytes will be done. In case of excess, the samples will be destroyed at the end of the study.

Late exsudative AMD with neovessels

Group Type: EXPERIMENTAL

Blood samples

Intervention Type: OTHER

: The blood sample from all groups will be taken on the day of inclusion, in the ophthalmology department. The patient will be cared for by a nurse and then taken to the collection room. A 100 ml sample will be taken (10 tubes of 10 ml). Blood samples will be labeled with the patient's identification number as part of the protocol. They will be transported to the research laboratory in order to be picked up for monocyte extraction. The purification of blood monocytes will be done. In case of excess, the samples will be destroyed at the end of the study.

Late AMD with macular atrophy without neovessels

Group Type: EXPERIMENTAL

Blood samples

Intervention Type: OTHER

: The blood sample from all groups will be taken on the day of inclusion, in the ophthalmology department. The patient will be cared for by a nurse and then taken to the collection room. A 100 ml sample will be taken (10 tubes of 10 ml). Blood samples will be labeled with the patient's identification number as part of the protocol. They will be transported to the research laboratory in order to be picked up for monocyte extraction. The purification of blood monocytes will be done. In case of excess, the samples will be destroyed at the end of the study.

Patientes with No AMD

Group Type: SHAM_COMPARATOR

Blood samples

Intervention Type: OTHER

: The blood sample from all groups will be taken on the day of inclusion, in the ophthalmology department. The patient will be cared for by a nurse and then taken to the collection room. A 100 ml sample will be taken (10 tubes of 10 ml). Blood samples will be labeled with the patient's identification number as part of the protocol. They will be transported to the research laboratory in order to be picked up for monocyte extraction. The purification of blood monocytes will be done. In case of excess, the samples will be destroyed at the end of the study.

Interventions

Blood samples

: The blood sample from all groups will be taken on the day of inclusion, in the ophthalmology department. The patient will be cared for by a nurse and then taken to the collection room. A 100 ml sample will be taken (10 tubes of 10 ml). Blood samples will be labeled with the patient's identification number as part of the protocol. They will be transported to the research laboratory in order to be picked up for monocyte extraction. The purification of blood monocytes will be done. In case of excess, the samples will be destroyed at the end of the study.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

General criteria:

• Male or female older than 50,
• Provide written informed consent,
• Patient affiliated to French social security,
• Maximum sampling volume (care + research) per 30-day period to be adapted according to the weight of the patient

Specific criteria:

Patient presenting in both eyes:

• Either the same type of AMD defined according to the modified international AREDS study (Ferris et al. 2013),
• or early AMD in one eye and atrophic AMD in the other eye, the patient will therefore be defined as being atrophic
• or early AMD in one eye and exudative AMD in the other eye, the patient will therefore be defined as exudative,
• or no retinal pathology (control group).

Exclusion Criteria

General criteria:

• Patient whose weight is less than 50kg,
• Adult patient under guardianship 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 atrophic AMD in one eye and exudative AMD in the other eye,
• Patient presenting with chronic retinal pathologies other than AMD, defined according to the modified international AREDS study (Ferris et al. 2013) , in the included eye,
• Patient taking systemic drugs with an immunomodulatory action: immunosuppressants, immunomodulators, chemotherapy or corticosteroids,
• Patient with systemic pathologies modifying their immune status,
• Patient with a history of diabetes,
• Patient who had dynamic phototherapy on the included eye.

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thibaud Mathis, MD

Role: PRINCIPAL_INVESTIGATOR

Service d'Ophtalmologie Hospices Civils de Lyon Hôpital de la Croix Rousse

Locations

Hôpital Edouard Herriot

Lyon, , France

Site Status: RECRUITING

Service d'ophtalmologie-HOSPICES CIVILS DE LYON - Hôpital de la Croix-Rousse

Lyon, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Thibaud Mathis, MD

Role: CONTACT

thibaud.mathis@chu-lyon.fr

4 26 10 93 22 ext. +33

Christelle Szatanek

Role: CONTACT

christelle.szatanek@chu-lyon.fr

4 26 73 27 24 ext. +33

Facility Contacts

Christelle GILLI, Dr

Role: primary

christelle.gilli@chu-lyon.fr

+33472119513

Thibaud Mathis, MD

Role: primary

thibaud.mathis@chu-lyon.fr

4 26 10 93 22 ext. +33

Christelle SZATANEK

Role: backup

christelle.szatanek@chu-lyon.fr

4 26 73 27 24 ext. +33

Other Identifiers

69HCL20_0027

Identifier Type: -

Identifier Source: org_study_id