Stem Cells Therapy in Degenerative Diseases of the Retina

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test the safety and effectiveness of an autologous bone marrow-derived stem/progenitor cells administered intravitreously in the subjects with degenerative diseases of the retina.

Detailed Description
-----------------
Degenerative diseases of the retina are challenging for ophthalmologists. This is a common term that covers heterogenous group of diseases, f.e. retinitis pigmentosa, Stargardt disease, Best's disease or age related macular degeneration. Undetermined etiology, wide range of factors that may trigger the onset of the disease and modulate it's course impede the implementation of an effective treatment. Currently, a stem cells therapy seems to be promising option in patients with degenerative diseases of the retina. The purpose of this prospective, nonrandomized, open label, pilot study is to conduct the investigation of the safety and efficacy of intravitreal injection of autologous bone marrow-isolated stem/progenitor cells with different selected phenotypes into the subjects with degenerative diseases of the retina. Especially, this clinical trial is designated to test the therapeutic (pro-regenerative and neuro-protective) functions of different stem/progenitor cell populations able to secrete bioactive neurotrophic factors. All patients enrolled will have a documented history of degenerative disease of the retina prior to study enrollment. Next, autologous bone marrow-isolated stem/progenitor cells intravitreous injection will be performed. Finally, treatment safety, adverse events and exploratory parameters, including best corrected visual acuity, visual field and electroretinography parameters, to establish disease progression rate will be recorded throughout the duration of the post-treatment follow up period.

Official Title
-----------------
Stem Cells Therapy in Degenerative Diseases of the Retina

Conditions
-----------------
Retinal Degeneration, Retinitis Pigmentosa, Age Related Macular Degeneration, Stargardt Disease 1

Intervention / Treatment
-----------------
* Biological: Stem/progenitor cells transplantation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diagnosed degenerative disease of the retina, age 18-65 years, best corrected visual acuity max. 0,2 (Snellen letter chart), good understanding of the protocol and willingness to consent, signed informed consent. Exclusion Criteria: concomitant eye disease (glaucoma, etc.) concomitant of other systemic disease or diseases, inflammation (high protein or lymphocytosis in the CSF), active infections. diabetes, cardio-vascular disorders, cancer, autoimmune diseases, renal failure, impaired hepatic function, subject unwilling or unable to comply with the requirements of the protocol, patient has been treated previously with any cellular therapy,

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stem/progenitor cells transplantation<br>Intervention: A single intravitreal injection of autologous bone marrow-derived stem/progenitor cells will be performed. | Biological: Stem/progenitor cells transplantation<br>* Human autologous bone marrow-derived stem/progenitor cell transplantation administered as an intravitreal injection in patients with degenerative disease of retina.<br>|
| Sham Comparator: Standard treatment of degenerative disease of retina<br>Symptomatic treatment of degenerative disease of retina without biologic cell-based treatment | Biological: Stem/progenitor cells transplantation<br>* Human autologous bone marrow-derived stem/progenitor cell transplantation administered as an intravitreal injection in patients with degenerative disease of retina.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Confirm the safety of autologous bone marrow stem/progenitor cell intravitreal injection in enrolled patients by repeated follow-up over one year with clinical evaluations. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of autologous bone marrow stem/progenitor intravitreal injection in enrolled patients. | Best corrected visual acuity, ETDRS chart [number of letters] | 12 months | 
| Intraocular pressure | Pascal tonometer [mmHg] | 12 months | 
| Optic disk retinal nerve fiber layer | optical coherence tomography [um] | 12 months | 
| Central macular thickness | optical coherence tomography [um] | 12 months | 
| Ganglion cell complex thickness | optical coherence tomography [um] | 12 months | 
| Choroidal thickness | Enhanced depth imaging optical coherence tomography [um] | 12 months | 
| Choroidal volume | Enhanced depth imaging optical coherence tomography [mm3] | 12 months | 
| Computed perimetry (30-2 and 10-2 module) | mean deviation, pattern standard deviation [B] | 12 months | 
| Goldmann perimetry with color filters | [degrees] | 12 months | 
| Contrast sensitivity | Pelli-Robson chart [number of letters] | 12 months | 
| Function of the photoreceptors (rods and cones), inner retinal cells (bipolar and amacrine cells), and ganglion cells. | Electroretinography (ERG) examination: amplitude of a and b waves [V], culmination time of a and b waves [s], culmination time of q1-q3 waves [s]. | 12 months | 
| Function of the photoreceptors | Multifocal electroretinography (mfERG) examination: retinal response density [V/degree 2], culmination time of P1 wave in 6 rings [s]. | 12 months | 
| Function of ganglion cells | Pattern electroretinography (PERG) examination: amplitude of P50 and N95 waves [V], culmination time of P50 wave [s]. | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stem cells, Retinitis Pigmentosa, Age Related Macular Degeneration, Stargardt Disease, electroretinography