Stem Cells Therapy in Degenerative Diseases of the Retina

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.

Study Overview

• Status: Unknown
• Conditions: Retinal Degeneration; Retinitis Pigmentosa; Age Related Macular Degeneration; Stargardt Disease 1
• Intervention / Treatment: Biological: Stem/progenitor cells transplantation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Poland
  • Szczecin, Poland, 70-111
    • I Department of Ophthalmology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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,

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Pomeranian Medical University Szczecin
• Investigators: Study Chair: Bogusław Machaliński, MD, PhD, Pomeranian Medical University; Study Director: Anna Machalińska, MD, PhD, Pomeranian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2018
• Primary Completion (Anticipated): February 28, 2020
• Study Completion (Anticipated): March 31, 2020

Study Registration Dates

• First Submitted: November 3, 2018
• First Submitted That Met QC Criteria: December 8, 2018
• First Posted (Actual): December 12, 2018

Study Record Updates

• Last Update Posted (Actual): December 17, 2018
• Last Update Submitted That Met QC Criteria: December 14, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: stem cells; Retinitis Pigmentosa; Age Related Macular Degeneration; electroretinography; Stargardt Disease
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Retinal Dystrophies; Macular Degeneration; Retinitis; Retinitis Pigmentosa; Retinal Degeneration; Stargardt Disease
• Other Study ID Numbers: IKiKO-KB-0012/143/13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No