<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03772938</url>
  </required_header>
  <id_info>
    <org_study_id>IKiKO-KB-0012/143/13</org_study_id>
    <nct_id>NCT03772938</nct_id>
  </id_info>
  <brief_title>Stem Cells Therapy in Degenerative Diseases of the Retina</brief_title>
  <official_title>Stem Cells Therapy in Degenerative Diseases of the Retina</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pomeranian Medical University Szczecin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pomeranian Medical University Szczecin</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test the safety and effectiveness of an autologous bone&#xD;
      marrow-derived stem/progenitor cells administered intravitreously in the subjects with&#xD;
      degenerative diseases of the retina.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Degenerative diseases of the retina are challenging for ophthalmologists. This is a common&#xD;
      term that covers heterogenous group of diseases, f.e. retinitis pigmentosa, Stargardt&#xD;
      disease, Best's disease or age related macular degeneration. Undetermined etiology, wide&#xD;
      range of factors that may trigger the onset of the disease and modulate it's course impede&#xD;
      the implementation of an effective treatment. Currently, a stem cells therapy seems to be&#xD;
      promising option in patients with degenerative diseases of the retina. The purpose of this&#xD;
      prospective, nonrandomized, open label, pilot study is to conduct the investigation of the&#xD;
      safety and efficacy of intravitreal injection of autologous bone marrow-isolated&#xD;
      stem/progenitor cells with different selected phenotypes into the subjects with degenerative&#xD;
      diseases of the retina. Especially, this clinical trial is designated to test the therapeutic&#xD;
      (pro-regenerative and neuro-protective) functions of different stem/progenitor cell&#xD;
      populations able to secrete bioactive neurotrophic factors. All patients enrolled will have a&#xD;
      documented history of degenerative disease of the retina prior to study enrollment. Next,&#xD;
      autologous bone marrow-isolated stem/progenitor cells intravitreous injection will be&#xD;
      performed. Finally, treatment safety, adverse events and exploratory parameters, including&#xD;
      best corrected visual acuity, visual field and electroretinography parameters, to establish&#xD;
      disease progression rate will be recorded throughout the duration of the post-treatment&#xD;
      follow up period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date type="Actual">December 13, 2018</start_date>
  <completion_date type="Anticipated">March 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">February 28, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>12 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy of autologous bone marrow stem/progenitor intravitreal injection in enrolled patients.</measure>
    <time_frame>12 months</time_frame>
    <description>Best corrected visual acuity, ETDRS chart [number of letters]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraocular pressure</measure>
    <time_frame>12 months</time_frame>
    <description>Pascal tonometer [mmHg]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Optic disk retinal nerve fiber layer</measure>
    <time_frame>12 months</time_frame>
    <description>optical coherence tomography [um]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Central macular thickness</measure>
    <time_frame>12 months</time_frame>
    <description>optical coherence tomography [um]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ganglion cell complex thickness</measure>
    <time_frame>12 months</time_frame>
    <description>optical coherence tomography [um]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Choroidal thickness</measure>
    <time_frame>12 months</time_frame>
    <description>Enhanced depth imaging optical coherence tomography [um]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Choroidal volume</measure>
    <time_frame>12 months</time_frame>
    <description>Enhanced depth imaging optical coherence tomography [mm3]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Computed perimetry (30-2 and 10-2 module)</measure>
    <time_frame>12 months</time_frame>
    <description>mean deviation, pattern standard deviation [B]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Goldmann perimetry with color filters</measure>
    <time_frame>12 months</time_frame>
    <description>[degrees]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Contrast sensitivity</measure>
    <time_frame>12 months</time_frame>
    <description>Pelli-Robson chart [number of letters]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Function of the photoreceptors (rods and cones), inner retinal cells (bipolar and amacrine cells), and ganglion cells.</measure>
    <time_frame>12 months</time_frame>
    <description>Electroretinography (ERG) examination:&#xD;
amplitude of a and b waves [V],&#xD;
culmination time of a and b waves [s],&#xD;
culmination time of q1-q3 waves [s].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Function of the photoreceptors</measure>
    <time_frame>12 months</time_frame>
    <description>Multifocal electroretinography (mfERG) examination:&#xD;
retinal response density [V/degree 2],&#xD;
culmination time of P1 wave in 6 rings [s].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Function of ganglion cells</measure>
    <time_frame>12 months</time_frame>
    <description>Pattern electroretinography (PERG) examination:&#xD;
amplitude of P50 and N95 waves [V],&#xD;
culmination time of P50 wave [s].</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Retinal Degeneration</condition>
  <condition>Retinitis Pigmentosa</condition>
  <condition>Age Related Macular Degeneration</condition>
  <condition>Stargardt Disease 1</condition>
  <arm_group>
    <arm_group_label>Stem/progenitor cells transplantation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intervention: A single intravitreal injection of autologous bone marrow-derived stem/progenitor cells will be performed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard treatment of degenerative disease of retina</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Symptomatic treatment of degenerative disease of retina without biologic cell-based treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Stem/progenitor cells transplantation</intervention_name>
    <description>Human autologous bone marrow-derived stem/progenitor cell transplantation administered as an intravitreal injection in patients with degenerative disease of retina.</description>
    <arm_group_label>Standard treatment of degenerative disease of retina</arm_group_label>
    <arm_group_label>Stem/progenitor cells transplantation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  diagnosed degenerative disease of the retina,&#xD;
&#xD;
          -  age 18-65 years,&#xD;
&#xD;
          -  best corrected visual acuity max. 0,2 (Snellen letter chart),&#xD;
&#xD;
          -  good understanding of the protocol and willingness to consent,&#xD;
&#xD;
          -  signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  concomitant eye disease (glaucoma, etc.)&#xD;
&#xD;
          -  concomitant of other systemic disease or diseases,&#xD;
&#xD;
          -  inflammation (high protein or lymphocytosis in the CSF), active infections.&#xD;
&#xD;
          -  diabetes,&#xD;
&#xD;
          -  cardio-vascular disorders,&#xD;
&#xD;
          -  cancer,&#xD;
&#xD;
          -  autoimmune diseases,&#xD;
&#xD;
          -  renal failure,&#xD;
&#xD;
          -  impaired hepatic function,&#xD;
&#xD;
          -  subject unwilling or unable to comply with the requirements of the protocol,&#xD;
&#xD;
          -  patient has been treated previously with any cellular therapy,&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bogusław Machaliński, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Pomeranian Medical University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anna Machalińska, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Pomeranian Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>I Department of Ophthalmology</name>
      <address>
        <city>Szczecin</city>
        <zip>70-111</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>November 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 8, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>December 14, 2018</last_update_submitted>
  <last_update_submitted_qc>December 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Pomeranian Medical University Szczecin</investigator_affiliation>
    <investigator_full_name>Marta P. Wiącek</investigator_full_name>
    <investigator_title>MD, PhD candidate, principal investigator</investigator_title>
  </responsible_party>
  <keyword>stem cells</keyword>
  <keyword>Retinitis Pigmentosa</keyword>
  <keyword>Age Related Macular Degeneration</keyword>
  <keyword>Stargardt Disease</keyword>
  <keyword>electroretinography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Degeneration</mesh_term>
    <mesh_term>Retinitis</mesh_term>
    <mesh_term>Retinitis Pigmentosa</mesh_term>
    <mesh_term>Retinal Degeneration</mesh_term>
    <mesh_term>Stargardt Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03772938
org study id: IKiKO-KB-0012/143/13
nct id: NCT03772938
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 12 months
description: 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.
measure: Efficacy of autologous bone marrow stem/progenitor intravitreal injection in enrolled patients.
time frame: 12 months
description: Best corrected visual acuity, ETDRS chart [number of letters]
measure: Intraocular pressure
time frame: 12 months
description: Pascal tonometer [mmHg]
measure: Optic disk retinal nerve fiber layer
time frame: 12 months
description: optical coherence tomography [um]
measure: Central macular thickness
time frame: 12 months
description: optical coherence tomography [um]
measure: Ganglion cell complex thickness
time frame: 12 months
description: optical coherence tomography [um]
measure: Choroidal thickness
time frame: 12 months
description: Enhanced depth imaging optical coherence tomography [um]
measure: Choroidal volume
time frame: 12 months
description: Enhanced depth imaging optical coherence tomography [mm3]
measure: Computed perimetry (30-2 and 10-2 module)
time frame: 12 months
description: mean deviation, pattern standard deviation [B]
measure: Goldmann perimetry with color filters
time frame: 12 months
description: [degrees]
measure: Contrast sensitivity
time frame: 12 months
description: Pelli-Robson chart [number of letters]
measure: Function of the photoreceptors (rods and cones), inner retinal cells (bipolar and amacrine cells), and ganglion cells.
time frame: 12 months
description: 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].
measure: Function of the photoreceptors
time frame: 12 months
description: Multifocal electroretinography (mfERG) examination:
retinal response density [V/degree 2],
culmination time of P1 wave in 6 rings [s].
measure: Function of ganglion cells
time frame: 12 months
description: Pattern electroretinography (PERG) examination:
amplitude of P50 and N95 waves [V],
culmination time of P50 wave [s].
arm group label: Stem/progenitor cells transplantation
arm group type: Active Comparator
description: Intervention: A single intravitreal injection of autologous bone marrow-derived stem/progenitor cells will be performed.
arm group label: Standard treatment of degenerative disease of retina
arm group type: Sham Comparator
description: Symptomatic treatment of degenerative disease of retina without biologic cell-based treatment
intervention type: Biological
intervention name: Stem/progenitor cells transplantation
description: Human autologous bone marrow-derived stem/progenitor cell transplantation administered as an intravitreal injection in patients with degenerative disease of retina.
arm group label: Standard treatment of degenerative disease of retina
arm group label: Stem/progenitor cells transplantation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Bogusław Machaliński, MD, PhD
role: Study Chair
affiliation: Pomeranian Medical University
last name: Anna Machalińska, MD, PhD
role: Study Director
affiliation: Pomeranian Medical University
facility: 
country: Poland
responsible party type: Principal Investigator
investigator affiliation: Pomeranian Medical University Szczecin
investigator full name: Marta P. Wiącek
investigator title: MD, PhD candidate, principal investigator
mesh term: Macular Degeneration
mesh term: Retinitis
mesh term: Retinitis Pigmentosa
mesh term: Retinal Degeneration
mesh term: Stargardt Disease
sharing ipd: No