Brief Title
Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia
Official Title
Randomized Controlled Trial of Pyridoxine for Tardive Dyskinesia
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 .
Study Type
Interventional
Primary Outcome
Mean Difference in AIMS scores
Secondary Outcome
Mean Difference in Barnes Akathisia Rating Scale Scores
Condition
Tardive Dyskinesia
Intervention
Pyridoxine
Study Arms / Comparison Groups
Pyridoxine
Description: Pyridoxine will be administered in dosages of 200 mg with a maximum dose of 400 mg.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Dietary Supplement
Estimated Enrollment
50
Start Date
December 1, 2017
Completion Date
June 30, 2021
Primary Completion Date
June 1, 2021
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.
Gender
All
Ages
18 Years - 80 Years
Accepts Healthy Volunteers
No
Contacts
Lars F Jarskog, MD, 919-843-7683, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03287778
Organization ID
17-1500
Responsible Party
Sponsor
Study Sponsor
University of North Carolina, Chapel Hill
Collaborators
Foundation of Hope, North Carolina
Study Sponsor
Lars F Jarskog, MD, Principal Investigator, University of North Carolina, Chapel Hill
Verification Date
March 2021