<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/NCT03758118</url>
  </required_header>
  <id_info>
    <org_study_id>85356727</org_study_id>
    <nct_id>NCT03758118</nct_id>
  </id_info>
  <brief_title>Citicoline in Non-Arteritic Ischemic Optic Neuropathy</brief_title>
  <official_title>Neuroprotection and Neuroenhancement in a Model of Optic Nerve Neurodegeneration (Non Arteritic Ischemic Optic Neuropathy): Study of Morpho-functional Changes Related to Treatment With Citicoline Oral Solution</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione G.B. Bietti, IRCCS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione G.B. Bietti, IRCCS</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 investigators tested the hypothesis whether the treatment with Citicoline in oral&#xD;
      solution (OS-Citicoline) would increase or stabilize visual acuity, retinal ganglion cells&#xD;
      (RGCs) function and neural conduction along the visual pathways (neuroenhancement), and/or&#xD;
      induce preservation of RGCs fibers' loss (neuroprotection) in an human model of&#xD;
      neurodegeneration: non-arteritic ischemic optic neuropathy (NAION).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators enrolled 36 patients with bilateral or monolateral NAION and 20 age similar&#xD;
      controls. Nineteen NAION patients received 500 mg/day of OS-Citicoline for a 6-months period&#xD;
      followed by 3-months of wash-out (NC Group); 17 NAION patients were not treated (NN Group)&#xD;
      from baseline up to 9 months. We assessed in all subjects at baseline, at 6 and 9-months of&#xD;
      follow-up: Visual acuity (VA), Pattern Electroretinogram (PERG), Visual Evoked Potentials&#xD;
      (VEP), retinal nerve fiber layer thickness (RNFL-T) and Humphrey 24-2 visual field mean&#xD;
      deviation (HFA MD). Mean differences were statistically evaluated by ANOVA between Groups,&#xD;
      and correlations were verified by Pearson's test.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 20, 2017</start_date>
  <completion_date type="Actual">July 25, 2017</completion_date>
  <primary_completion_date type="Actual">July 25, 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stabilization or amelioration of Visual Acuity</measure>
    <time_frame>0-9 months</time_frame>
    <description>Visual Acuity measured as LogMAR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stabilization or amelioration of Retinal Ganglion Cells function</measure>
    <time_frame>0-9 months</time_frame>
    <description>Pattern-Electroretinogram recordings. The main parameter is the P50-N95 amplitude measured in microvolt.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stabilization or amelioration of optic nerve function</measure>
    <time_frame>0-9 months</time_frame>
    <description>Visual Evoked Potentials recordings. The main parameter is the P100 Implicit time measured in milliseconds</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stabilization or amelioration of optic nerve morphology</measure>
    <time_frame>0-9 months</time_frame>
    <description>Assessment of Retinal Nerve Fiber Thickness by Optical Coherence Tomography measured in micron</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stabilization or amelioration of the visual field</measure>
    <time_frame>0-9 months</time_frame>
    <description>evaluation of the visual field by static perimetry (the main indexes are Mean Deviation and Pattern Standard Deviation measured in dB).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Non-arteritic Ischemic Optic Neuropathy</condition>
  <arm_group>
    <arm_group_label>NAION patients OS-Citicoline treated</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In a group of patients with NAION, OS-Citicoline will be administered (500 mg/day) for 6 months followed by three months of suspension</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NAION patients untreated</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>In one group of patients with NAION no type of treatment will be performed during 9 months of observation</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Citicoline</intervention_name>
    <description>Citicoline administered in oral solution</description>
    <arm_group_label>NAION patients OS-Citicoline treated</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Acute visual reduction episode from NAION occurring for more than 6 months&#xD;
&#xD;
          2. Typical defects of the visual field evidenced with the Goldmann perimetry or with&#xD;
             Humphrey perimetry 30-2&#xD;
&#xD;
          3. Visual acuity not less than 1/10&#xD;
&#xD;
          4. Having suspended any potential neuroprotective therapies (e.g., Coenzyme Q10) for at&#xD;
             least 6 months.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Ocular surgery in the 3 months preceding the study, including surgery for cataracts in&#xD;
             the previous three months.&#xD;
&#xD;
          -  Cataract or maculopathy&#xD;
&#xD;
          -  Known hypersensitivity to the study product&#xD;
&#xD;
          -  Positive history for diseases of the optic nerve (retrobulbar optic neuropathy,&#xD;
             glaucoma) or systemic diseases which could preclude the enrolment in the study&#xD;
             according to the investigators' judgement&#xD;
&#xD;
          -  Pregnant or nursing women, or women of potential childbearing age not using adequate&#xD;
             contraception.&#xD;
&#xD;
          -  Diabetes, SLE, rheumatoid arthritis, mixed connective tissue disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vincenzo MF Parisi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione Bietti- IRCCS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Britannico Hospital</name>
      <address>
        <city>Roma</city>
        <zip>00184</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>Carelli V, La Morgia C, Ross-Cisneros FN, Sadun AA. Optic neuropathies: the tip of the neurodegeneration iceberg. Hum Mol Genet. 2017 Oct 1;26(R2):R139-R150. doi: 10.1093/hmg/ddx273.</citation>
    <PMID>28977448</PMID>
  </results_reference>
  <results_reference>
    <citation>Cho YS. The role of necroptosis in the treatment of diseases. BMB Rep. 2018 May;51(5):219-224. doi: 10.5483/bmbrep.2018.51.5.074.</citation>
    <PMID>29636122</PMID>
  </results_reference>
  <results_reference>
    <citation>Hayreh SS, Zimmerman B. Visual field abnormalities in nonarteritic anterior ischemic optic neuropathy: their pattern and prevalence at initial examination. Arch Ophthalmol. 2005 Nov;123(11):1554-62. doi: 10.1001/archopht.123.11.1554.</citation>
    <PMID>16286618</PMID>
  </results_reference>
  <results_reference>
    <citation>Patel HR, Margo CE. Pathology of Ischemic Optic Neuropathy. Arch Pathol Lab Med. 2017 Jan;141(1):162-166. doi: 10.5858/arpa.2016-0027-RS.</citation>
    <PMID>28029908</PMID>
  </results_reference>
  <results_reference>
    <citation>Parisi V, Gallinaro G, Ziccardi L, Coppola G. Electrophysiological assessment of visual function in patients with non-arteritic ischaemic optic neuropathy. Eur J Neurol. 2008 Aug;15(8):839-45. doi: 10.1111/j.1468-1331.2008.02200.x. Epub 2008 Jun 28.</citation>
    <PMID>18557920</PMID>
  </results_reference>
  <results_reference>
    <citation>Balducci N, Morara M, Veronese C, Barboni P, Casadei NL, Savini G, Parisi V, Sadun AA, Ciardella A. Optical coherence tomography angiography in acute arteritic and non-arteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2017 Nov;255(11):2255-2261. doi: 10.1007/s00417-017-3774-y. Epub 2017 Aug 31.</citation>
    <PMID>28861697</PMID>
  </results_reference>
  <results_reference>
    <citation>Khalilpour S, Latifi S, Behnammanesh G, Majid AMSA, Majid ASA, Tamayol A. Ischemic optic neuropathy as a model of neurodegenerative disorder: A review of pathogenic mechanism of axonal degeneration and the role of neuroprotection. J Neurol Sci. 2017 Apr 15;375:430-441. doi: 10.1016/j.jns.2016.12.044. Epub 2016 Dec 26.</citation>
    <PMID>28320183</PMID>
  </results_reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>November 27, 2018</last_update_submitted>
  <last_update_submitted_qc>November 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Citicoline</keyword>
  <keyword>Non-arteritic ischemic optic neuropathy</keyword>
  <keyword>Neuroprotection</keyword>
  <keyword>Neuroenhancement</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Nervous System Diseases</mesh_term>
    <mesh_term>Optic Nerve Diseases</mesh_term>
    <mesh_term>Optic Neuropathy, Ischemic</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytidine Diphosphate Choline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 20, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT03758118/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>November 28, 2018</submitted>
    <returned>March 18, 2019</returned>
    <submitted>March 20, 2019</submitted>
    <returned>June 19, 2019</returned>
    <submitted>June 20, 2019</submitted>
    <returned>August 2, 2019</returned>
    <submitted>February 12, 2020</submitted>
    <returned>February 25, 2020</returned>
    <submitted>February 2, 2021</submitted>
    <returned>February 18, 2021</returned>
    <submitted>February 14, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03758118
org study id: 85356727
nct id: NCT03758118
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The investigators tested the hypothesis whether the treatment with Citicoline in oral
      solution (OS-Citicoline) would increase or stabilize visual acuity, retinal ganglion cells
      (RGCs) function and neural conduction along the visual pathways (neuroenhancement), and/or
      induce preservation of RGCs fibers' loss (neuroprotection) in an human model of
      neurodegeneration: non-arteritic ischemic optic neuropathy (NAION).
The investigators enrolled 36 patients with bilateral or monolateral NAION and 20 age similar
      controls. Nineteen NAION patients received 500 mg/day of OS-Citicoline for a 6-months period
      followed by 3-months of wash-out (NC Group); 17 NAION patients were not treated (NN Group)
      from baseline up to 9 months. We assessed in all subjects at baseline, at 6 and 9-months of
      follow-up: Visual acuity (VA), Pattern Electroretinogram (PERG), Visual Evoked Potentials
      (VEP), retinal nerve fiber layer thickness (RNFL-T) and Humphrey 24-2 visual field mean
      deviation (HFA MD). Mean differences were statistically evaluated by ANOVA between Groups,
      and correlations were verified by Pearson's test.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Stabilization or amelioration of Visual Acuity
time frame: 0-9 months
description: Visual Acuity measured as LogMAR
measure: Stabilization or amelioration of Retinal Ganglion Cells function
time frame: 0-9 months
description: Pattern-Electroretinogram recordings. The main parameter is the P50-N95 amplitude measured in microvolt.
measure: Stabilization or amelioration of optic nerve function
time frame: 0-9 months
description: Visual Evoked Potentials recordings. The main parameter is the P100 Implicit time measured in milliseconds
measure: Stabilization or amelioration of optic nerve morphology
time frame: 0-9 months
description: Assessment of Retinal Nerve Fiber Thickness by Optical Coherence Tomography measured in micron
measure: Stabilization or amelioration of the visual field
time frame: 0-9 months
description: evaluation of the visual field by static perimetry (the main indexes are Mean Deviation and Pattern Standard Deviation measured in dB).
arm group label: NAION patients OS-Citicoline treated
arm group type: Active Comparator
description: In a group of patients with NAION, OS-Citicoline will be administered (500 mg/day) for 6 months followed by three months of suspension
arm group label: NAION patients untreated
arm group type: No Intervention
description: In one group of patients with NAION no type of treatment will be performed during 9 months of observation
intervention type: Dietary Supplement
intervention name: Citicoline
description: Citicoline administered in oral solution
arm group label: NAION patients OS-Citicoline treated
criteria: 
gender: All
minimum age: 45 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Vincenzo MF Parisi, MD
role: Principal Investigator
affiliation: Fondazione Bietti- IRCCS
facility: 
country: Italy
citation: Carelli V, La Morgia C, Ross-Cisneros FN, Sadun AA. Optic neuropathies: the tip of the neurodegeneration iceberg. Hum Mol Genet. 2017 Oct 1;26(R2):R139-R150. doi: 10.1093/hmg/ddx273.
PMID: 28977448
citation: Cho YS. The role of necroptosis in the treatment of diseases. BMB Rep. 2018 May;51(5):219-224. doi: 10.5483/bmbrep.2018.51.5.074.
PMID: 29636122
citation: Hayreh SS, Zimmerman B. Visual field abnormalities in nonarteritic anterior ischemic optic neuropathy: their pattern and prevalence at initial examination. Arch Ophthalmol. 2005 Nov;123(11):1554-62. doi: 10.1001/archopht.123.11.1554.
PMID: 16286618
citation: Patel HR, Margo CE. Pathology of Ischemic Optic Neuropathy. Arch Pathol Lab Med. 2017 Jan;141(1):162-166. doi: 10.5858/arpa.2016-0027-RS.
PMID: 28029908
citation: Parisi V, Gallinaro G, Ziccardi L, Coppola G. Electrophysiological assessment of visual function in patients with non-arteritic ischaemic optic neuropathy. Eur J Neurol. 2008 Aug;15(8):839-45. doi: 10.1111/j.1468-1331.2008.02200.x. Epub 2008 Jun 28.
PMID: 18557920
citation: Balducci N, Morara M, Veronese C, Barboni P, Casadei NL, Savini G, Parisi V, Sadun AA, Ciardella A. Optical coherence tomography angiography in acute arteritic and non-arteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2017 Nov;255(11):2255-2261. doi: 10.1007/s00417-017-3774-y. Epub 2017 Aug 31.
PMID: 28861697
citation: Khalilpour S, Latifi S, Behnammanesh G, Majid AMSA, Majid ASA, Tamayol A. Ischemic optic neuropathy as a model of neurodegenerative disorder: A review of pathogenic mechanism of axonal degeneration and the role of neuroprotection. J Neurol Sci. 2017 Apr 15;375:430-441. doi: 10.1016/j.jns.2016.12.044. Epub 2016 Dec 26.
PMID: 28320183
responsible party type: Sponsor
mesh term: Peripheral Nervous System Diseases
mesh term: Optic Nerve Diseases
mesh term: Optic Neuropathy, Ischemic
mesh term: Ischemia
mesh term: Cytidine Diphosphate Choline
sharing ipd: No
provided document: 
submitted: November 28, 2018
returned: March 18, 2019
submitted: March 20, 2019
returned: June 19, 2019
submitted: June 20, 2019
returned: August 2, 2019
submitted: February 12, 2020
returned: February 25, 2020
submitted: February 2, 2021
returned: February 18, 2021
submitted: February 14, 2023