<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/NCT02212678</url>
  </required_header>
  <id_info>
    <org_study_id>1406M51207</org_study_id>
    <secondary_id>123269</secondary_id>
    <nct_id>NCT02212678</nct_id>
  </id_info>
  <brief_title>Repeated-Dose Oral N-acetylcysteine for the Treatment of Parkinson's Disease</brief_title>
  <official_title>Repeated-Dose Oral N-acetylcysteine for the Treatment of Parkinson's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Parkinson's Disease Society of the United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are interested in evaluating the use of oral N-acetylcysteine (NAC) as&#xD;
      therapy for Parkinson's Disease (PD) and measuring changes in brain and blood chemistry.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators are interested in evaluating the use of oral N-acetylcysteine (NAC) as&#xD;
      therapy for Parkinson's Disease (PD) and measuring changes in brain and blood chemistry. The&#xD;
      investigators' hypothesis is that repeated oral dosing of NAC will result in increased brain&#xD;
      and red blood cell GSH concentrations in individuals with Parkinson's disease (PD) and&#xD;
      healthy controls. The specific aims are to 1.) measure plasma and blood (red blood cell)&#xD;
      glutathione (GSH) and ratio of reduced GSH to oxidized glutathione (GSSG) in individuals with&#xD;
      PD and healthy controls at baseline and after four weeks of repeated high doses of oral NAC&#xD;
      (6000 mg/day) and 2) measure cortical GSH levels (as ascertained through MRS) in those with&#xD;
      PD and healthy controls at baseline and four weeks during repeated high doses of oral NAC&#xD;
      (6000 mg/day) simultaneously with Aim 1. This study will combine information from a medical&#xD;
      history, a physical examination, and disease rating scales with results obtained using&#xD;
      Magnetic Resonance Spectroscopy (MRS) brain scans and pharmacokinetic studies from blood&#xD;
      samples. This research will require 2 visits, one at baseline and one after approximately 28&#xD;
      days of therapy. Participants will provide their medical history during the first visit, and&#xD;
      undergo a physical examination and rating scale each visit (duration: 1 hour). The first&#xD;
      visit including the brain scans and blood collection will require approximately 3 hours of&#xD;
      time. The brain scan and pharmacokinetic studies for the second visit will require&#xD;
      approximately 8 hours of time. In total the second visit will take roughly 9 hours.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</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>Glutathione (GSH) Brain Levels</measure>
    <time_frame>pre-dose and after approximately 28 days of treatment</time_frame>
    <description>GSH levels in brain of all subjects at baseline and post-NAC (n-acetylcysteine) dosing as measured by magnetic resonance spectroscopy (MRS)</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>N-acetylcysteine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be provided 6000 mg/day of N-acetylcysteine (capsule) to be divided into 2 equal daily doses and taken orally for approximately 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-acetylcysteine capsule</intervention_name>
    <description>N-acetylcysteine capsule</description>
    <arm_group_label>N-acetylcysteine</arm_group_label>
    <other_name>NAC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All participants must be 18 years or older&#xD;
&#xD;
          2. All enrollees must understand and cooperate with requirements of the study in the&#xD;
             opinion of the investigators and must be able to provide written informed consent&#xD;
&#xD;
          3. Individuals with medically stable Parkinson's disease (in the opinion of the&#xD;
             investigator)&#xD;
&#xD;
          4. All participants must not have taken antioxidants NAC, glutathione, coenzyme Q-10,&#xD;
             vitamin C, or vitamin E for 3 weeks prior to the study&#xD;
&#xD;
          5. Absence of dementia in all subjects&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to undergo MRI scanning without sedation and other MRI counterindications,&#xD;
             such as metal in the body (see section 7.3)&#xD;
&#xD;
          2. Medically unstable conditions as determined by the investigators&#xD;
&#xD;
          3. Pregnant or lactating or those women of child-bearing age that are not using&#xD;
             acceptable forms of contraception&#xD;
&#xD;
          4. Diagnosis of asthma that is presently being treated with any medication, or past&#xD;
             history of asthma/bronchospasm resulting in an emergency room visit, hospitalization&#xD;
             or treatment&#xD;
&#xD;
          5. Unable to adhere to study protocol for whatever reason&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul Tuite, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lisa Coles, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>August 4, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <results_first_submitted>April 23, 2019</results_first_submitted>
  <results_first_submitted_qc>April 23, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 16, 2019</results_first_posted>
  <last_update_submitted>April 23, 2019</last_update_submitted>
  <last_update_submitted_qc>April 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>N-acetylcysteine</title>
          <description>Subjects will be provided 6000 mg/day of N-acetylcysteine (capsule) to be divided into 2 equal daily doses and taken orally for approximately 28 days&#xD;
N-acetylcysteine capsule: N-acetylcysteine capsule</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>N-acetylcysteine</title>
          <description>Subjects will be provided 6000 mg/day of N-acetylcysteine (capsule) to be divided into 2 equal daily doses and taken orally for approximately 28 days&#xD;
N-acetylcysteine capsule: N-acetylcysteine capsule</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71" spread="11"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Glutathione (GSH) Brain Levels</title>
        <description>GSH levels in brain of all subjects at baseline and post-NAC (n-acetylcysteine) dosing as measured by magnetic resonance spectroscopy (MRS)</description>
        <time_frame>pre-dose and after approximately 28 days of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>N-acetylcysteine</title>
            <description>Subjects will be provided 6000 mg/day of N-acetylcysteine (capsule) to be divided into 2 equal daily doses and taken orally for approximately 28 days&#xD;
N-acetylcysteine capsule: N-acetylcysteine capsule</description>
          </group>
        </group_list>
        <measure>
          <title>Glutathione (GSH) Brain Levels</title>
          <description>GSH levels in brain of all subjects at baseline and post-NAC (n-acetylcysteine) dosing as measured by magnetic resonance spectroscopy (MRS)</description>
          <units>mM</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.93" spread="0.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-NAC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.99" spread="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>N-acetylcysteine</title>
          <description>Subjects will be provided 6000 mg/day of N-acetylcysteine (capsule) to be divided into 2 equal daily doses and taken orally for approximately 28 days&#xD;
N-acetylcysteine capsule: N-acetylcysteine capsule</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="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>indigestion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>increased tremor</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="8"/>
              </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>Lisa Coles, MS, PhD</name_or_title>
      <organization>University of Minnesota</organization>
      <phone>4109264788</phone>
      <email>durh0016@umn.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/NCT02212678
org study id: 1406M51207
secondary id: 123269
nct id: NCT02212678
lead sponsor: 
collaborator: 
has dmc: Yes
The investigators are interested in evaluating the use of oral N-acetylcysteine (NAC) as
      therapy for Parkinson's Disease (PD) and measuring changes in brain and blood chemistry.
The investigators are interested in evaluating the use of oral N-acetylcysteine (NAC) as
      therapy for Parkinson's Disease (PD) and measuring changes in brain and blood chemistry. The
      investigators' hypothesis is that repeated oral dosing of NAC will result in increased brain
      and red blood cell GSH concentrations in individuals with Parkinson's disease (PD) and
      healthy controls. The specific aims are to 1.) measure plasma and blood (red blood cell)
      glutathione (GSH) and ratio of reduced GSH to oxidized glutathione (GSSG) in individuals with
      PD and healthy controls at baseline and after four weeks of repeated high doses of oral NAC
      (6000 mg/day) and 2) measure cortical GSH levels (as ascertained through MRS) in those with
      PD and healthy controls at baseline and four weeks during repeated high doses of oral NAC
      (6000 mg/day) simultaneously with Aim 1. This study will combine information from a medical
      history, a physical examination, and disease rating scales with results obtained using
      Magnetic Resonance Spectroscopy (MRS) brain scans and pharmacokinetic studies from blood
      samples. This research will require 2 visits, one at baseline and one after approximately 28
      days of therapy. Participants will provide their medical history during the first visit, and
      undergo a physical examination and rating scale each visit (duration: 1 hour). The first
      visit including the brain scans and blood collection will require approximately 3 hours of
      time. The brain scan and pharmacokinetic studies for the second visit will require
      approximately 8 hours of time. In total the second visit will take roughly 9 hours.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Glutathione (GSH) Brain Levels
time frame: pre-dose and after approximately 28 days of treatment
description: GSH levels in brain of all subjects at baseline and post-NAC (n-acetylcysteine) dosing as measured by magnetic resonance spectroscopy (MRS)
arm group label: N-acetylcysteine
arm group type: Experimental
description: Subjects will be provided 6000 mg/day of N-acetylcysteine (capsule) to be divided into 2 equal daily doses and taken orally for approximately 28 days
intervention type: Drug
intervention name: N-acetylcysteine capsule
description: N-acetylcysteine capsule
arm group label: N-acetylcysteine
other name: NAC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paul Tuite, MD
role: Principal Investigator
affiliation: University of Minnesota
last name: Lisa Coles, PhD
role: Principal Investigator
affiliation: University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 