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Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia

Primary Purpose

Tardive Dyskinesia, Antipsychotic Agents

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Pyridoxine
Placebo
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tardive Dyskinesia focused on measuring 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

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Meet Schooler - Kane criteria for TD (at least one muscle group is rated at "moderate" severity or at least two muscle groups are rated at "mild" severity).
  • Subjects must have > or equal to 3 months of antipsychotic exposure.
  • Other causes of involuntary movements have been ruled out.
  • Psychiatrically stable as defined by outpatient status for > or equal to 2 months.
  • No change in dopamine antagonist agent or dose for > or equal to 2 months or change in other prescribed medications for > or equal to 1 month prior to enrollment
  • Patients must be 18-80 years of age.
  • Patients must demonstrate adequate decisional capacity to make a choice about participating in this research study and must provide written informed consent to participate.
  • Women who can become pregnant must be using an adequate method of contraception to avoid pregnancy throughout the study. Acceptable methods include oral, injectable or implanted contraceptives, intrauterine devices or barrier methods such as condoms, diaphragm and spermicides. Women who can become pregnant must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test at the Screening Visit.

Exclusion Criteria:

  • Inpatient status
  • Clinical Global Impression Severity (CGI-S) score > or equal to 6.
  • Evidence of any medical condition(s) that could confound the presence of TD.
  • Currently taking more than 2 antipsychotic medications.
  • Currently taking levodopa.
  • Current or prior treatment with valbenazine or deutetrabenazine within the past 3 months.
  • Current or prior treatment with pyridoxine within the past 3 months.
  • Women who are pregnant or breastfeeding.
  • Alcohol use disorder as determined by the SCID within the past month.
  • Substance use disorder (except caffeine and nicotine) as determined by the SCID within the past month.
  • No serious and unstable medical condition(s) in the judgment of the investigator.
  • DSM-V diagnosis of intellectual disability, moderate or greater severity; or diagnosis of major neurocognitive disorder.

Sites / Locations

  • University of North Carolina at Chapel Hill

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Pyridoxine

Placebo

Arm Description

Pyridoxine will be administered in dosages of 200 mg with a maximum dose of 400 mg.

Matching placebos will be administered for each active drug.

Outcomes

Primary Outcome Measures

Mean Difference in AIMS scores
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.

Secondary Outcome Measures

Mean Difference in Barnes Akathisia Rating Scale Scores
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.
Mean Difference in Simpson Angus Scale Scores
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.

Full Information

First Posted
September 15, 2017
Last Updated
March 13, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Foundation of Hope, North Carolina
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1. Study Identification

Unique Protocol Identification Number
NCT03287778
Brief Title
Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia
Official Title
Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
December 1, 2017 (Actual)
Primary Completion Date
December 30, 2022 (Actual)
Study Completion Date
December 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Foundation of Hope, North Carolina

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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 .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tardive Dyskinesia, Antipsychotic Agents
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pyridoxine
Arm Type
Active Comparator
Arm Description
Pyridoxine will be administered in dosages of 200 mg with a maximum dose of 400 mg.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebos will be administered for each active drug.
Intervention Type
Dietary Supplement
Intervention Name(s)
Pyridoxine
Other Intervention Name(s)
Vitamin B6
Intervention Description
Max dose of 400 mg QD PO
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar pill
Intervention Description
Matching placebos will be administered.
Primary Outcome Measure Information:
Title
Mean Difference in AIMS scores
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.
Time Frame
Baseline, Week 8
Secondary Outcome Measure Information:
Title
Mean Difference in Barnes Akathisia Rating Scale Scores
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.
Time Frame
Baseline, Week 8
Title
Mean Difference in Simpson Angus Scale Scores
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.
Time Frame
Baseline, Week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Meet Schooler - Kane criteria for TD (at least one muscle group is rated at "moderate" severity or at least two muscle groups are rated at "mild" severity). Subjects must have > or equal to 3 months of antipsychotic exposure. Other causes of involuntary movements have been ruled out. Psychiatrically stable as defined by outpatient status for > or equal to 2 months. No change in dopamine antagonist agent or dose for > or equal to 2 months or change in other prescribed medications for > or equal to 1 month prior to enrollment Patients must be 18-80 years of age. Patients must demonstrate adequate decisional capacity to make a choice about participating in this research study and must provide written informed consent to participate. Women who can become pregnant must be using an adequate method of contraception to avoid pregnancy throughout the study. Acceptable methods include oral, injectable or implanted contraceptives, intrauterine devices or barrier methods such as condoms, diaphragm and spermicides. Women who can become pregnant must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test at the Screening Visit. Exclusion Criteria: Inpatient status Clinical Global Impression Severity (CGI-S) score > or equal to 6. Evidence of any medical condition(s) that could confound the presence of TD. Currently taking more than 2 antipsychotic medications. Currently taking levodopa. Current or prior treatment with valbenazine or deutetrabenazine within the past 3 months. Current or prior treatment with pyridoxine within the past 3 months. Women who are pregnant or breastfeeding. Alcohol use disorder as determined by the SCID within the past month. Substance use disorder (except caffeine and nicotine) as determined by the SCID within the past month. No serious and unstable medical condition(s) in the judgment of the investigator. DSM-V diagnosis of intellectual disability, moderate or greater severity; or diagnosis of major neurocognitive disorder.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lars F Jarskog, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11532741
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.
Results Reference
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Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia

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