<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/NCT03287778</url>
  </required_header>
  <id_info>
    <org_study_id>17-1500</org_study_id>
    <nct_id>NCT03287778</nct_id>
  </id_info>
  <brief_title>Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia</brief_title>
  <official_title>Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Foundation of Hope, North Carolina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Purpose: Tardive dyskinesia (TD) is a involuntary movement disorder that can occur following&#xD;
      long term treatment with antipsychotic medications and for which few treatment options exist.&#xD;
      This study will test the efficacy of pyridoxine (also known as vitamin B6) for TD. This will&#xD;
      be an 8 week double-blind, placebo-controlled, randomized trial measuring the effect of&#xD;
      pyridoxine 400 mg/day on the severity of involuntary muscle movements in people who meet&#xD;
      Schooler-Kane criteria for TD.&#xD;
&#xD;
      Participants: Approximately 50 subjects will be recruited from the UNC Schizophrenia&#xD;
      Treatment and Evaluation Program (STEP) and other local psychiatric clinics.&#xD;
&#xD;
      Procedures (methods): Symptoms of TD will be assessed using the Abnormal Involuntary Movement&#xD;
      Scale (AIMS). Pharmacological Intervention: All participants who meet entry criteria will be&#xD;
      randomized to one of two treatment groups: pyridoxine or placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Overview of Procedures: All procedures will be conducted at either the University of North&#xD;
      Carolina Hospitals in Chapel Hill, or at the North Carolina Psychiatric Research Center&#xD;
      (NCPRC), a specialized program of the University of North Carolina Center for Excellence in&#xD;
      Community Mental Health, in Raleigh.&#xD;
&#xD;
      Screening: During the initial clinic visit and after providing written informed consent,&#xD;
      prospective subjects' psychiatric and medical histories will be reviewed, physical exams&#xD;
      conducted, demographics and vital signs obtained, and blood and urine collected. The&#xD;
      Structured Clinical Interview for DSM-V, the Columbia Suicide Severity Rating Scale (C-SSRS),&#xD;
      and the Clinical Global Impressions-Severity (CGI-S) will be used to evaluate&#xD;
      psychopathology. Involuntary muscle movements will be assessed using the Abnormal Involuntary&#xD;
      Movement Scale (AIMS). The AIMS exam will be video recorded. Other neurological side effects&#xD;
      of antipsychotic medications will be assessed using the Barnes Akathisia Scale (BARS) and&#xD;
      Simpson-Angus Scale (SAS).&#xD;
&#xD;
      The baseline visit will be scheduled within 28 days of the screening visit. Vital signs and&#xD;
      weight will be measured. A blood test to measure baseline pyridoxine level will be collected.&#xD;
      A battery of assessments will be administered including the Clinical Global&#xD;
      Impressions-Severity (CGI-S), the Alcohol Use Scale, Substance Use Scale, Brief Psychiatric&#xD;
      Rating Scale (BPRS), Columbia Suicide Severity Rating Scale (C-SSRS), AIMS (video recorded),&#xD;
      BARS, and SAS.&#xD;
&#xD;
      At the completion of the baseline visit, subjects who continue to meet study inclusion&#xD;
      criteria will be randomized to one of two treatment groups (pyridoxine or placebo). Subjects&#xD;
      assigned to the pyridoxine group will receive 200 mg per day for one week and then 400 mg per&#xD;
      day, as tolerated, for the remainder of the study. Subjects assigned to the placebo group&#xD;
      will receive matching placebo capsules.&#xD;
&#xD;
      After study enrollment, subjects will be scheduled for Week 1 and Week 2 study visits. The&#xD;
      purpose of these visits will be to assess medication management (i.e., adverse events/side&#xD;
      effects, adherence), collect vital signs, assess current psychiatric status, and assess&#xD;
      neurological symptoms using the AIMS (video recorded), BARS, and SAS. The CGI-S will be&#xD;
      performed at both Week 1 and Week 2, however, the C-SSRS will be completed at Week 2 only.&#xD;
&#xD;
      Study visit at Week 4 and end-of-study visit at Week 8 will be similar to Week 2, with the&#xD;
      addition of the BPRS, Substance Use Scale and Alcohol Use Questionnaire. A blood test to&#xD;
      measure pyridoxine levels will also be collected during these visits. Study drug is&#xD;
      discontinued at the Week 8 visit.&#xD;
&#xD;
      A follow-up visit at Week 10, two weeks after stopping the treatment, will consist of&#xD;
      assessing for adverse events/side effects, collecting vital signs, administrating the CGI-S&#xD;
      and C-SSRS, and performing the AIMS (video recorded), BARS, and SAS. The follow-up visit will&#xD;
      help determine whether the potential benefits of pyridoxine for TD may continue after&#xD;
      treatment is discontinued.&#xD;
&#xD;
      Vital signs, adverse events, and side effects will be obtained at all in-person study visits.&#xD;
      Blood collection and laboratory testing will be done at Screening, Baseline, Week 4, and Week&#xD;
      8 .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2017</start_date>
  <completion_date type="Actual">December 30, 2022</completion_date>
  <primary_completion_date type="Actual">December 30, 2022</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Difference in AIMS scores</measure>
    <time_frame>Baseline, Week 8</time_frame>
    <description>Mean difference in Abnormal Involuntary Movement Scale (AIMS) total scores in participants assigned to pyridoxine and participants assigned to placebo from baseline to Week 8.&#xD;
The severity of TD symptoms is assessed by the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1 through 7). The AIMS total dyskinesia score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Difference in Barnes Akathisia Rating Scale Scores</measure>
    <time_frame>Baseline, Week 8</time_frame>
    <description>Mean difference in Barnes Akathisia Rating Scale (BARS) scores in participants assigned to pyridoxine and participants assigned to placebo from baseline to Week 8.&#xD;
Barnes Akathisia Scale (BARS) is a rating scale that is administered by physicians to assess the severity of drug-induced akathisia, which is a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion. The following subcategories are scored: objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness and are rated on a 4-point scale from 0 - 3. In addition, the global clinical assessment of akathisia uses a 6-point scale ranging from 0 - 5 (absent to severe). The total score ranges from 0 to 14 with a higher score indicating increased severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Difference in Simpson Angus Scale Scores</measure>
    <time_frame>Baseline, Week 8</time_frame>
    <description>Mean difference in Simpson Angus Scale (SAS) scores in participants assigned to pyridoxine and participants assigned to placebo from baseline to Week 8.&#xD;
The Simpson-Angus Scale (SAS) is a 10-item testing instrument used to evaluate drug-related extrapyramidal syndromes. The following items are included in the SAS: gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella reflex, tremor, and salivation. Total score ranges from 0 to 40 with a higher score indicating increased severity.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Tardive Dyskinesia</condition>
  <condition>Antipsychotic Agents</condition>
  <arm_group>
    <arm_group_label>Pyridoxine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pyridoxine will be administered in dosages of 200 mg with a maximum dose of 400 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebos will be administered for each active drug.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Pyridoxine</intervention_name>
    <description>Max dose of 400 mg QD PO</description>
    <arm_group_label>Pyridoxine</arm_group_label>
    <other_name>Vitamin B6</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebos will be administered.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Sugar pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Meet Schooler - Kane criteria for TD (at least one muscle group is rated at &quot;moderate&quot;&#xD;
             severity or at least two muscle groups are rated at &quot;mild&quot; severity).&#xD;
&#xD;
          -  Subjects must have &gt; or equal to 3 months of antipsychotic exposure.&#xD;
&#xD;
          -  Other causes of involuntary movements have been ruled out.&#xD;
&#xD;
          -  Psychiatrically stable as defined by outpatient status for &gt; or equal to 2 months.&#xD;
&#xD;
          -  No change in dopamine antagonist agent or dose for &gt; or equal to 2 months or change in&#xD;
             other prescribed medications for &gt; or equal to 1 month prior to enrollment&#xD;
&#xD;
          -  Patients must be 18-80 years of age.&#xD;
&#xD;
          -  Patients must demonstrate adequate decisional capacity to make a choice about&#xD;
             participating in this research study and must provide written informed consent to&#xD;
             participate.&#xD;
&#xD;
          -  Women who can become pregnant must be using an adequate method of contraception to&#xD;
             avoid pregnancy throughout the study. Acceptable methods include oral, injectable or&#xD;
             implanted contraceptives, intrauterine devices or barrier methods such as condoms,&#xD;
             diaphragm and spermicides. Women who can become pregnant must have a negative serum&#xD;
             beta human chorionic gonadotropin (β-HCG) pregnancy test at the Screening Visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inpatient status&#xD;
&#xD;
          -  Clinical Global Impression Severity (CGI-S) score &gt; or equal to 6.&#xD;
&#xD;
          -  Evidence of any medical condition(s) that could confound the presence of TD.&#xD;
&#xD;
          -  Currently taking more than 2 antipsychotic medications.&#xD;
&#xD;
          -  Currently taking levodopa.&#xD;
&#xD;
          -  Current or prior treatment with valbenazine or deutetrabenazine within the past 3&#xD;
             months.&#xD;
&#xD;
          -  Current or prior treatment with pyridoxine within the past 3 months.&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Alcohol use disorder as determined by the SCID within the past month.&#xD;
&#xD;
          -  Substance use disorder (except caffeine and nicotine) as determined by the SCID within&#xD;
             the past month.&#xD;
&#xD;
          -  No serious and unstable medical condition(s) in the judgment of the investigator.&#xD;
&#xD;
          -  DSM-V diagnosis of intellectual disability, moderate or greater severity; or diagnosis&#xD;
             of major neurocognitive disorder.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lars F Jarskog, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Lerner V, Miodownik C, Kaptsan A, Cohen H, Matar M, Loewenthal U, Kotler M. Vitamin B(6) in the treatment of tardive dyskinesia: a double-blind, placebo-controlled, crossover study. Am J Psychiatry. 2001 Sep;158(9):1511-4. doi: 10.1176/appi.ajp.158.9.1511.</citation>
    <PMID>11532741</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>September 15, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <last_update_submitted>March 13, 2023</last_update_submitted>
  <last_update_submitted_qc>March 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pyridoxine</keyword>
  <keyword>Vitamin B6</keyword>
  <keyword>Neurologic Manifestations</keyword>
  <keyword>Involuntary Movements</keyword>
  <keyword>Movement Disorder</keyword>
  <keyword>Dyskinesias</keyword>
  <keyword>Physiological Effects of Drugs</keyword>
  <keyword>Psychotic Disorders</keyword>
  <keyword>Schizophrenia Spectrum and Other Psychotic Disorders</keyword>
  <keyword>Signs and Symptoms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyskinesias</mesh_term>
    <mesh_term>Tardive Dyskinesia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pyridoxine</mesh_term>
    <mesh_term>Vitamin B 6</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03287778
org study id: 17-1500
nct id: NCT03287778
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Purpose: Tardive dyskinesia (TD) is a involuntary movement disorder that can occur following
      long term treatment with antipsychotic medications and for which few treatment options exist.
      This study will test the efficacy of pyridoxine (also known as vitamin B6) for TD. This will
      be an 8 week double-blind, placebo-controlled, randomized trial measuring the effect of
      pyridoxine 400 mg/day on the severity of involuntary muscle movements in people who meet
      Schooler-Kane criteria for TD.

      Participants: Approximately 50 subjects will be recruited from the UNC Schizophrenia
      Treatment and Evaluation Program (STEP) and other local psychiatric clinics.

      Procedures (methods): Symptoms of TD will be assessed using the Abnormal Involuntary Movement
      Scale (AIMS). Pharmacological Intervention: All participants who meet entry criteria will be
      randomized to one of two treatment groups: pyridoxine or placebo.
Overview of Procedures: All procedures will be conducted at either the University of North
      Carolina Hospitals in Chapel Hill, or at the North Carolina Psychiatric Research Center
      (NCPRC), a specialized program of the University of North Carolina Center for Excellence in
      Community Mental Health, in Raleigh.

      Screening: During the initial clinic visit and after providing written informed consent,
      prospective subjects' psychiatric and medical histories will be reviewed, physical exams
      conducted, demographics and vital signs obtained, and blood and urine collected. The
      Structured Clinical Interview for DSM-V, the Columbia Suicide Severity Rating Scale (C-SSRS),
      and the Clinical Global Impressions-Severity (CGI-S) will be used to evaluate
      psychopathology. Involuntary muscle movements will be assessed using the Abnormal Involuntary
      Movement Scale (AIMS). The AIMS exam will be video recorded. Other neurological side effects
      of antipsychotic medications will be assessed using the Barnes Akathisia Scale (BARS) and
      Simpson-Angus Scale (SAS).

      The baseline visit will be scheduled within 28 days of the screening visit. Vital signs and
      weight will be measured. A blood test to measure baseline pyridoxine level will be collected.
      A battery of assessments will be administered including the Clinical Global
      Impressions-Severity (CGI-S), the Alcohol Use Scale, Substance Use Scale, Brief Psychiatric
      Rating Scale (BPRS), Columbia Suicide Severity Rating Scale (C-SSRS), AIMS (video recorded),
      BARS, and SAS.

      At the completion of the baseline visit, subjects who continue to meet study inclusion
      criteria will be randomized to one of two treatment groups (pyridoxine or placebo). Subjects
      assigned to the pyridoxine group will receive 200 mg per day for one week and then 400 mg per
      day, as tolerated, for the remainder of the study. Subjects assigned to the placebo group
      will receive matching placebo capsules.

      After study enrollment, subjects will be scheduled for Week 1 and Week 2 study visits. The
      purpose of these visits will be to assess medication management (i.e., adverse events/side
      effects, adherence), collect vital signs, assess current psychiatric status, and assess
      neurological symptoms using the AIMS (video recorded), BARS, and SAS. The CGI-S will be
      performed at both Week 1 and Week 2, however, the C-SSRS will be completed at Week 2 only.

      Study visit at Week 4 and end-of-study visit at Week 8 will be similar to Week 2, with the
      addition of the BPRS, Substance Use Scale and Alcohol Use Questionnaire. A blood test to
      measure pyridoxine levels will also be collected during these visits. Study drug is
      discontinued at the Week 8 visit.

      A follow-up visit at Week 10, two weeks after stopping the treatment, will consist of
      assessing for adverse events/side effects, collecting vital signs, administrating the CGI-S
      and C-SSRS, and performing the AIMS (video recorded), BARS, and SAS. The follow-up visit will
      help determine whether the potential benefits of pyridoxine for TD may continue after
      treatment is discontinued.

      Vital signs, adverse events, and side effects will be obtained at all in-person study visits.
      Blood collection and laboratory testing will be done at Screening, Baseline, Week 4, and Week
      8 .
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean Difference in AIMS scores
time frame: Baseline, Week 8
description: Mean difference in Abnormal Involuntary Movement Scale (AIMS) total scores in participants assigned to pyridoxine and participants assigned to placebo from baseline to Week 8.
The severity of TD symptoms is assessed by the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1 through 7). The AIMS total dyskinesia score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity.
measure: Mean Difference in Barnes Akathisia Rating Scale Scores
time frame: Baseline, Week 8
description: Mean difference in Barnes Akathisia Rating Scale (BARS) scores in participants assigned to pyridoxine and participants assigned to placebo from baseline to Week 8.
Barnes Akathisia Scale (BARS) is a rating scale that is administered by physicians to assess the severity of drug-induced akathisia, which is a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion. The following subcategories are scored: objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness and are rated on a 4-point scale from 0 - 3. In addition, the global clinical assessment of akathisia uses a 6-point scale ranging from 0 - 5 (absent to severe). The total score ranges from 0 to 14 with a higher score indicating increased severity.
measure: Mean Difference in Simpson Angus Scale Scores
time frame: Baseline, Week 8
description: Mean difference in Simpson Angus Scale (SAS) scores in participants assigned to pyridoxine and participants assigned to placebo from baseline to Week 8.
The Simpson-Angus Scale (SAS) is a 10-item testing instrument used to evaluate drug-related extrapyramidal syndromes. The following items are included in the SAS: gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, glabella reflex, tremor, and salivation. Total score ranges from 0 to 40 with a higher score indicating increased severity.
arm group label: Pyridoxine
arm group type: Active Comparator
description: Pyridoxine will be administered in dosages of 200 mg with a maximum dose of 400 mg.
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebos will be administered for each active drug.
intervention type: Dietary Supplement
intervention name: Pyridoxine
description: Max dose of 400 mg QD PO
arm group label: Pyridoxine
other name: Vitamin B6
intervention type: Dietary Supplement
intervention name: Placebo
description: Matching placebos will be administered.
arm group label: Placebo
other name: Sugar pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Lars F Jarskog, MD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
country: United States
citation: Lerner V, Miodownik C, Kaptsan A, Cohen H, Matar M, Loewenthal U, Kotler M. Vitamin B(6) in the treatment of tardive dyskinesia: a double-blind, placebo-controlled, crossover study. Am J Psychiatry. 2001 Sep;158(9):1511-4. doi: 10.1176/appi.ajp.158.9.1511.
PMID: 11532741
responsible party type: Sponsor
mesh term: Dyskinesias
mesh term: Tardive Dyskinesia
mesh term: Pyridoxine
mesh term: Vitamin B 6