Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia
Condition: Tardive Dyskinesia; Antipsychotic Agents
MeSH terms: Dyskinesias; Tardive Dyskinesia
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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 .
    

Intervention name(s): Pyridoxine; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Max dose of 400 mg QD PO; Matching placebos will be administered.
Other intervention name(s): Vitamin B6; Sugar pill
Intervention MeSH terms: Pyridoxine; Vitamin B 6
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Pyridoxine; Vitamin B6; Neurologic Manifestations; Involuntary Movements; Movement Disorder; Dyskinesias; Physiological Effects of Drugs; Psychotic Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Signs and Symptoms