- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03790345
Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics
Effect of Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics
Study Overview
Status
Intervention / Treatment
Detailed Description
D2 dopaminergic receptor blockers, used to treat schizophrenia, can lead to the onset of drug-induced movement disorders, such as parkinsonism, dystonia, dyskinesia and akathisia. They seem to be associated with oxidative stress, as a result of an increase in free radicals generated from dopamine metabolism. A preclinical study showed that vitamin B6 (pyridoxine) and B12 (cobalamin), alone or in combination, prevented the development of orofacial dyskinesia induced by haloperidol in an animal model of schizophrenia.
Specific Aim1: To conduct a prospective, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of 12-week adjuvant treatment with 200mg of pyridoxine (B6) or 2mg of cobalamin (B12) to treat drug-induced movement disorders of patients with schizophrenia, schizoaffective or bipolar disorder. The investigators will randomly assign 45 patients into three groups: placebo, B6 or B12 and check whether administration of vitamin B6 (pyridoxine) or B12 (cobalamin) attenuates drug-induced movement disorders (IDDM) in patients with diagnosis of schizophrenia, schizoaffective or bipolar disorder.
Specific Aim 2: To quantify changes in serum markers of inflammation and biomarkers of oxidative stress in response to adjunctive treatment with B6 or B12. The hypothesis is that changes in these biomarkers will mediate the clinical response to them.
Research Plan: The investigators will carry out a proof of concept 12-week prospective, randomized, double-blind, controlled trial of vitamin B6 and B12, at doses of 200 mg/day and 2mg/day, respectively, or identical placebo tablets, added to ongoing antipsychotics in 45 stable patients (ages 18-60 years, 15 patients per group) with diagnosis of schizophrenia, schizoaffective or bipolar disorder. The study will be conducted at the Drug Research and Development Center (NPDM), at the Universidade Federal do Ceará, Fortaleza, Brazil. This center has a long history of performing placebocontrolled trials in clinical medicine (http://www.npdm.ufc.br/) and has the necessary infrastructure to successfully complete the proposed study protocol. All participants will give written informed consent prior to study enrollment.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Lia LO Sanders, MD, PhD
- Phone Number: +55(85)3366-8338
- Email: lia_sanders@hotmail.com
Study Locations
-
-
CE
-
Fortaleza, CE, Brazil, 60430-275
- Recruiting
- Núcleo de Pesquisa e Desenvolvimento de Medicamentos - UFC
-
Contact:
- Lia LO Sanders, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Capacity to provide informed consent;
- Schizophrenia diagnosis (confirmed by Structured Clinical Interview (SCID);
- Movement disorders induced by psychotropic drugs of at least moderate severity;
- Exposure to psychotropic medication for at least three months prior of the appearance of movement disorders;.
- Disorders of movement for at least one year;
- Stable psychotropic regimen for at least one month prior to study entry.
Exclusion Criteria:
- 6-month history of any drug or alcohol abuse or dependence;
- Changes in psychotropic medications within the last 4 weeks;
- General medical illness including autoimmune disorders, known chronic infections such as HIV or hepatitis C, and liver or renal failure that could adversely impact on patient outcome;
- Women who are planning to become pregnant, are pregnant, or are breastfeeding.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Experimental group 1
15 subjects will be randomly assigned to adjuvant treatment with 200mg of vitamin B6 (pyridoxine).
|
Adjuvant daily treatment with 200mg of pyridoxine
Other Names:
|
Experimental: Experimental group 2
15 subjects will be randomly assigned to adjuvant treatment with 2mg of vitamin B12 (cobalamin).
|
Adjuvant daily treatment with 2mg of cobalamin
Other Names:
|
Sham Comparator: Placebo oral tablet
15 subjects will be randomly assigned to adjuvant treatment with placebo.
|
Adjuvant daily treatment with placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in the Simpson-Angus Extrapyramidal Symptoms Scale (SAS) scores
Time Frame: Baseline and 12 weeks
|
10-item rating scale to assess extrapyramidal symptoms; each item is scored 0-4, yielding a total between 0 and 40.
|
Baseline and 12 weeks
|
Change in the Barnes Akathisia Rating Scale (BAS, BARS) scores
Time Frame: Baseline and 12 weeks
|
Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness are rated on a 4-point scale from 0 - 3 and are summed yielding a total score ranging from 0 to 9. The Global Clinical Assessment of Akathisia uses a 5-point scale ranging from 0 - 4.
|
Baseline and 12 weeks
|
Change in the Abnormal Involuntary Movement Scale (AIMS) scores
Time Frame: Baseline and 12 weeks
|
10-item rating scale to assess involuntary movements; items are rated on a five-point scale of severity from 0-4, yielding a total between 0 and 40.
|
Baseline and 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in the Brief Psychiatry Rating Scale (BPRS) scores
Time Frame: Baseline and 12 weeks
|
18-item rating scale to assess changes in psychopathology; each item is scored 0-6, yielding a total between 0 and 40.
|
Baseline and 12 weeks
|
Change in Plasma Glutathione (GSH)
Time Frame: Baseline and 12 weeks
|
GSH in ng/mL
|
Baseline and 12 weeks
|
Change in serum level of Nitrite
Time Frame: Baseline and 12 weeks
|
Nitrite in nanomole/mililiter
|
Baseline and 12 weeks
|
Change in serum level of Thiobarbituric acid reactive substances (TBARS)
Time Frame: Baseline and 12 weeks
|
TBARS in mmol of malonaldehyde/mL
|
Baseline and 12 weeks
|
Change in serum level of Interleukin 1 β (IL-1β)
Time Frame: Baseline and 12 weeks
|
IL-1β in pg/mL
|
Baseline and 12 weeks
|
Change in serum level of Interleukin-4
Time Frame: Baseline and 12 weeks
|
IL-4 in pg/mL
|
Baseline and 12 weeks
|
Change in serum level of Interferon gamma (IFNγ)
Time Frame: Baseline and 12 weeks
|
IFNγ in pg/mL
|
Baseline and 12 weeks
|
Change in serum level of Tumor necrosis factor alpha (TNF-α)
Time Frame: Baseline and 12 weeks
|
TNF-α in pg/mL
|
Baseline and 12 weeks
|
Change in Indoleamine 2,3-dioxygenase (IDO) enzymatic activity
Time Frame: Baseline and 12 weeks
|
IDO activity in U IDO mol^-1/mg^-1
|
Baseline and 12 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Lia LO Sanders, MD, PhD, Núcleo de Pesquisa e Desenvolvimento de Medicamentos
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- B12B16study
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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