Tardive DyskinesiaNCT03287778
Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia
A study testing Pyridoxine in people with Tardive Dyskinesia and Antipsychotic Agents, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Tardive Dyskinesia, Antipsychotic Agents
- What is being tested?
- Pyridoxine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2017to 30 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
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.
Read the 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 .
- Conditions
- Tardive Dyskinesia, Antipsychotic Agents
- Being tested
- Pyridoxine, Placebo
- 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
- Medical subject headings
- Tardive Dyskinesia, Neurologic Manifestations, Dyskinesias, Movement Disorders, Psychotic Disorders, Schizophrenia Spectrum and Other Psychotic Disorders, Signs and Symptoms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyridoxineDietary supplement
Also called Vitamin B6
Max dose of 400 mg QD PO
PlaceboDietary supplement
Also called Sugar pill
Matching placebos will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Pyridoxine | Active comparator | Pyridoxine will be administered in dosages of 200 mg with a maximum dose of 400 mg. Receives: Dietary Supplement: Pyridoxine |
| Placebo | Placebo comparator | Matching placebos will be administered for each active drug. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 8
Secondary outcomes (2)
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.
Measured: Baseline, Week 8
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.
Measured: Baseline, Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2017
- Study start1 Dec 2017
- Primary completion30 Dec 2022
- Study completion30 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tardive DyskinesiaStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation of Hope, North Carolina
- Responsible party
- Sponsor
- Investigators
- Lars F Jarskog, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03287778
- Sponsor's protocol ID
- 17-1500
- Status last verified
- Mar 2023
- First submitted
- 15 Sep 2017
- Last updated
- 14 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 11532741
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia
- ClinicalTrials.gov ID
- NCT03287778
- Acronym / sponsor ID
- 17-1500
- Conditions
- Tardive Dyskinesia, Antipsychotic Agents
- Keywords
- Pyridoxine, Vitamin B6, Neurologic Manifestations, Involuntary Movements, Movement Disorder, Dyskinesias, Physiological Effects of Drugs, Psychotic Disorders
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Foundation of Hope, North Carolina
- Study start
- 1 Dec 2017 (actual)
- Primary completion
- 30 Dec 2022 (actual)
- Study completion
- 30 Dec 2022 (actual)
- First posted
- 19 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pyridoxine | Active comparator | Dietary Supplement: PyridoxinePyridoxine will be administered in dosages of 200 mg with a maximum dose of 400 mg. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboMatching placebos will be administered for each active drug. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PyridoxineAlso: Vitamin B6Max dose of 400 mg QD PO | Dietary supplement | Pyridoxine |
| PlaceboAlso: Sugar pillMatching placebos will be administered. | Dietary supplement | Placebo |
Primary outcome
Mean Difference in AIMS scores
Time frame: Baseline, Week 8
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.
2 secondary outcomes
Mean Difference in Barnes Akathisia Rating Scale Scores
Time frame: Baseline, Week 8
Mean Difference in Simpson Angus Scale Scores
Time frame: Baseline, Week 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2023.
- Background: PubMed 11532741Lerner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lars F Jarskog, MD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pyridoxine in people with Tardive Dyskinesia and Antipsychotic Agents, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Difference in AIMS scores (time frame: Baseline, Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03287778, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2023.