<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/NCT01663935</url>
  </required_header>
  <id_info>
    <org_study_id>2016-1576</org_study_id>
    <secondary_id>2012-0023</secondary_id>
    <nct_id>NCT01663935</nct_id>
  </id_info>
  <brief_title>Vision Response to Dopamine Replacement</brief_title>
  <official_title>Interventional Study of Levodopa Replacement on Retinal Function in Oculocutaneous Albinism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Wisconsin, Madison</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate and document physiologic and functional changes in&#xD;
      visual performance and retinal function of patients diagnosed with albinism (a dopamine&#xD;
      deficiency state) following a trial of oral Levodopa/carbidopa treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study the investigators propose that the retina itself in albinism is deficient in&#xD;
      dopamine, and vision improvement will occur as a result of improved retinal function in&#xD;
      response to the deficient neurotransmitter dopamine. This study has a pretest-posttest design&#xD;
      in order to determine if improvement in vision is in response to replacement of deficiency&#xD;
      (dopamine). The electroretinography (ERG) testing and optical coherence tomography (OCT) will&#xD;
      be critical determinants to confirm vision improvement as a result of improved retinal&#xD;
      function, but are not primary outcome data. Main outcome measures will be collected at&#xD;
      pre-treatment, 1 month, 3 months, and 4 months. Change in visual acuity as measured in logMAR&#xD;
      by Snellen or sweep visual evoked potential (SVEP) after 3 months of treatment is the primary&#xD;
      outcome. Patients include OCA1a patients, OCA1b, OCA2, and unclassified Oculocutaneous&#xD;
      albinism (OCA). OCA1a patients clinically are known to have the worst vision, and&#xD;
      physiologically have the lowest (or absent) levels of tyrosinase function (Dopamine&#xD;
      Production). All patients will be treated with Levodopa/carbidopa 4mg/kg/day in three divided&#xD;
      doses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of funding&#xD;
  </why_stopped>
  <start_date type="Actual">October 17, 2012</start_date>
  <completion_date type="Actual">April 12, 2018</completion_date>
  <primary_completion_date type="Actual">April 12, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Visual Acuity Change</measure>
    <time_frame>3 months</time_frame>
    <description>Change in visual acuity from baseline to 3 months as measured in logMAR by Snellen or Sweep visual evoked potential (SVEP). logMar lower values equals better visual outcome.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Contrast Sensitivity</measure>
    <time_frame>3 months</time_frame>
    <description>Ancillary testing of visual/retinal function with contrast sensitivity testing. Contrast sensitivity testing measures how well the eyes can distinguish between finer and finer light increments compared to dark. This test is a chart with different capital letters organized in horizontal lines. The contrast decreases with each line. The person will move down the chart to determine the least level of contrast they can see.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Albinism</condition>
  <condition>Oculocutaneous Albinism</condition>
  <arm_group>
    <arm_group_label>Levodopa/carbidopa 4mg/kg/day</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Treatment drug taken orally three times daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levodopa/carbidopa</intervention_name>
    <description>This study will have an intent to treat goal. Anyone that fits the inclusion criteria for the study will be entered and receive study drug.</description>
    <arm_group_label>Levodopa/carbidopa 4mg/kg/day</arm_group_label>
    <other_name>Sinemet</other_name>
    <other_name>Atamet</other_name>
    <other_name>Parcopa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  clinical diagnosis of oculocutaneous albinism&#xD;
&#xD;
          -  age over 3 and weight over 25 lbs.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ocular only albinism&#xD;
&#xD;
          -  ocular pathology other than albinism&#xD;
&#xD;
          -  neurologic disease, history of myocardial infarction, history of clinical depression,&#xD;
             pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael C Struck, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Wisconsin</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>August 9, 2012</study_first_submitted>
  <study_first_submitted_qc>August 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 14, 2012</study_first_posted>
  <results_first_submitted>April 9, 2019</results_first_submitted>
  <results_first_submitted_qc>May 17, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 11, 2019</results_first_posted>
  <last_update_submitted>May 17, 2019</last_update_submitted>
  <last_update_submitted_qc>May 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>levodopa</keyword>
  <keyword>Albinism</keyword>
  <keyword>dopamine</keyword>
  <keyword>oculocutaneous albinism</keyword>
  <keyword>vision</keyword>
  <keyword>retina function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Albinism</mesh_term>
    <mesh_term>Albinism, Oculocutaneous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Levodopa</mesh_term>
    <mesh_term>Carbidopa</mesh_term>
  </intervention_browse>
  <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>September 5, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/35/NCT01663935/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Levodopa/Carbidopa 4mg/kg/Day</title>
          <description>Treatment drug taken orally three times daily&#xD;
Levodopa/carbidopa: This study will have an intent to treat goal. Anyone that fits the inclusion criteria for the study will be entered and receive study drug.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Levodopa/Carbidopa 4mg/kg/Day</title>
          <description>Treatment drug taken orally three times daily&#xD;
Levodopa/carbidopa: This study will have an intent to treat goal. Anyone that fits the inclusion criteria for the study will be entered and receive study drug.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race/Ethnicity</title>
              <category_list>
                <category>
                  <title>Non hispanic or latino/ white</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>non hispanic or latino/ asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>hispanic or latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Visual Acuity Change</title>
        <description>Change in visual acuity from baseline to 3 months as measured in logMAR by Snellen or Sweep visual evoked potential (SVEP). logMar lower values equals better visual outcome.</description>
        <time_frame>3 months</time_frame>
        <population>participants pre and post treatment per protocol</population>
        <group_list>
          <group group_id="O1">
            <title>Levodopa/Carbidopa 4mg/kg/Day</title>
            <description>Treatment drug taken orally three times daily&#xD;
Levodopa/carbidopa: This study will have an intent to treat goal. Anyone that fits the inclusion criteria for the study will be entered and receive study drug.</description>
          </group>
        </group_list>
        <measure>
          <title>Visual Acuity Change</title>
          <description>Change in visual acuity from baseline to 3 months as measured in logMAR by Snellen or Sweep visual evoked potential (SVEP). logMar lower values equals better visual outcome.</description>
          <population>participants pre and post treatment per protocol</population>
          <units>logMar</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".774" spread=".207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Contrast Sensitivity</title>
        <description>Ancillary testing of visual/retinal function with contrast sensitivity testing. Contrast sensitivity testing measures how well the eyes can distinguish between finer and finer light increments compared to dark. This test is a chart with different capital letters organized in horizontal lines. The contrast decreases with each line. The person will move down the chart to determine the least level of contrast they can see.</description>
        <time_frame>3 months</time_frame>
        <population>participants pre and post medication per protocol for contrast sensitivity. Range could be anywhere from a score of 0 to 75 for each eye. The higher the score the more letters they could see in low contrast.</population>
        <group_list>
          <group group_id="O1">
            <title>Levodopa/Carbidopa 4mg/kg/Day</title>
            <description>Treatment drug taken orally three times daily&#xD;
Levodopa/carbidopa: This study will have an intent to treat goal. Anyone that fits the inclusion criteria for the study will be entered and receive study drug.</description>
          </group>
        </group_list>
        <measure>
          <title>Contrast Sensitivity</title>
          <description>Ancillary testing of visual/retinal function with contrast sensitivity testing. Contrast sensitivity testing measures how well the eyes can distinguish between finer and finer light increments compared to dark. This test is a chart with different capital letters organized in horizontal lines. The contrast decreases with each line. The person will move down the chart to determine the least level of contrast they can see.</description>
          <population>participants pre and post medication per protocol for contrast sensitivity. Range could be anywhere from a score of 0 to 75 for each eye. The higher the score the more letters they could see in low contrast.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>eyes</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>eyes</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.7" spread="21.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected for each patient starting at baseline through the month 4 study follow up visit.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Levodopa/Carbidopa 4mg/kg/Day</title>
          <description>Treatment drug taken orally three times daily&#xD;
Levodopa/carbidopa: This study will have an intent to treat goal. Anyone that fits the inclusion criteria for the study will be entered and receive study drug.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Michael Struck</name_or_title>
      <organization>University of Wisconsin, Madison</organization>
      <phone>608 263-6429</phone>
      <email>mcstruck@wisc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01663935
org study id: 2016-1576
secondary id: 2012-0023
nct id: NCT01663935
lead sponsor: 
has dmc: No
The purpose of the study is to evaluate and document physiologic and functional changes in
      visual performance and retinal function of patients diagnosed with albinism (a dopamine
      deficiency state) following a trial of oral Levodopa/carbidopa treatment.
In this study the investigators propose that the retina itself in albinism is deficient in
      dopamine, and vision improvement will occur as a result of improved retinal function in
      response to the deficient neurotransmitter dopamine. This study has a pretest-posttest design
      in order to determine if improvement in vision is in response to replacement of deficiency
      (dopamine). The electroretinography (ERG) testing and optical coherence tomography (OCT) will
      be critical determinants to confirm vision improvement as a result of improved retinal
      function, but are not primary outcome data. Main outcome measures will be collected at
      pre-treatment, 1 month, 3 months, and 4 months. Change in visual acuity as measured in logMAR
      by Snellen or sweep visual evoked potential (SVEP) after 3 months of treatment is the primary
      outcome. Patients include OCA1a patients, OCA1b, OCA2, and unclassified Oculocutaneous
      albinism (OCA). OCA1a patients clinically are known to have the worst vision, and
      physiologically have the lowest (or absent) levels of tyrosinase function (Dopamine
      Production). All patients will be treated with Levodopa/carbidopa 4mg/kg/day in three divided
      doses.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Visual Acuity Change
time frame: 3 months
description: Change in visual acuity from baseline to 3 months as measured in logMAR by Snellen or Sweep visual evoked potential (SVEP). logMar lower values equals better visual outcome.
measure: Contrast Sensitivity
time frame: 3 months
description: Ancillary testing of visual/retinal function with contrast sensitivity testing. Contrast sensitivity testing measures how well the eyes can distinguish between finer and finer light increments compared to dark. This test is a chart with different capital letters organized in horizontal lines. The contrast decreases with each line. The person will move down the chart to determine the least level of contrast they can see.
arm group label: Levodopa/carbidopa 4mg/kg/day
arm group type: Other
description: Treatment drug taken orally three times daily
intervention type: Drug
intervention name: Levodopa/carbidopa
description: This study will have an intent to treat goal. Anyone that fits the inclusion criteria for the study will be entered and receive study drug.
arm group label: Levodopa/carbidopa 4mg/kg/day
other name: Sinemet
other name: Atamet
other name: Parcopa
criteria: 
gender: All
minimum age: 3 Years
maximum age: N/A
healthy volunteers: No
last name: Michael C Struck, MD
role: Principal Investigator
affiliation: University of Wisconsin, Madison
facility: 
country: United States
responsible party type: Sponsor
mesh term: Albinism
mesh term: Albinism, Oculocutaneous
mesh term: Levodopa
mesh term: Carbidopa
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 