Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics

Schizophrenia Clinical Trial

Official title:

Effect of Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03790345
• Other study ID #: B12B16study
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 3, 2019
• Est. completion date: November 3, 2021

Study information

• Verified date: December 2018
• Source: Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara
• Contact: Lia LO Sanders, MD, PhD
• Phone: +55(85)3366-8338
• Email: lia_sanders[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

D2 dopaminergic receptor blockers, used to treat schizophrenia, can lead to the onset of movement disorders. Drug-induced movement disorders encompass several syndromes. Parkinsonism, dystonia, dyskinesia and akathisia are the most prevalent. All of them lead to poor adherence to the treatment instituted, decrease in the quality of life, relapses and hospitalizations. The pathophysiology of drug-induced movement disorders is complex and poorly understood, but seems to be associated with oxidative stress, as a result of an increase in free radicals generated from dopamine metabolism. Treatment strategies following the onset of drug-induced movement disorders include neuroleptic discontinuation, use of atypical antipsychotics and anticholinergics. A pre-clinical study showed that the antioxidant properties of vitamins B6 and B12, alone or in combination, prevented the development of orofacial dyskinesia induced by haloperidol. This clinical trial aims to evaluate the effects of vitamins B6 and B12 on the treatment of patients diagnosed with schizophrenia, schizoaffective or bipolar disorder who present with tardive dyskinesia, dystonia and parkinsonism.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: November 3, 2021
• Est. primary completion date: June 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Disease
• Drug Induced Movement Disorder, Unspecified
• Movement Disorders
• Oxidative Stress
• Schizophrenia

Intervention

Drug:
• Pyridoxine
Adjuvant daily treatment with 200mg of pyridoxine
• Cobalamin
Adjuvant daily treatment with 2mg of cobalamin
• Placebo Oral Tablet
Adjuvant daily treatment with placebo

Locations

Country	Name	City	State
Brazil	Núcleo de Pesquisa e Desenvolvimento de Medicamentos - UFC	Fortaleza	CE

Sponsors (1)

Lead Sponsor	Collaborator
Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Simpson-Angus Extrapyramidal Symptoms Scale (SAS) scores	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
Primary	Change in the Barnes Akathisia Rating Scale (BAS, BARS) scores	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
Primary	Change in the Abnormal Involuntary Movement Scale (AIMS) scores	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	Change in the Brief Psychiatry Rating Scale (BPRS) scores	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
Secondary	Change in Plasma Glutathione (GSH)	GSH in ng/mL	Baseline and 12 weeks
Secondary	Change in serum level of Nitrite	Nitrite in nanomole/mililiter	Baseline and 12 weeks
Secondary	Change in serum level of Thiobarbituric acid reactive substances (TBARS)	TBARS in mmol of malonaldehyde/mL	Baseline and 12 weeks
Secondary	Change in serum level of Interleukin 1 ß (IL-1ß)	IL-1ß in pg/mL	Baseline and 12 weeks
Secondary	Change in serum level of Interleukin-4	IL-4 in pg/mL	Baseline and 12 weeks
Secondary	Change in serum level of Interferon gamma (IFN?)	IFN? in pg/mL	Baseline and 12 weeks
Secondary	Change in serum level of Tumor necrosis factor alpha (TNF-a)	TNF-a in pg/mL	Baseline and 12 weeks
Secondary	Change in Indoleamine 2,3-dioxygenase (IDO) enzymatic activity	IDO activity in U IDO mol^-1/mg^-1	Baseline and 12 weeks