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

NCT ID: NCT03790345

Last Updated: 2019-12-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-03
• Study Completion Date: 2021-11-03

Brief 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.

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.

Conditions

Schizophrenia; Drug Induced Movement Disorder, Unspecified; Oxidative Stress

Keywords

Schizophrenia; Cobalamin; Pyridoxine; Drug-induced movement disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental group 1

15 subjects will be randomly assigned to adjuvant treatment with 200mg of vitamin B6 (pyridoxine).

Group Type: EXPERIMENTAL

Pyridoxine

Intervention Type: DRUG

Adjuvant daily treatment with 200mg of pyridoxine

Experimental group 2

15 subjects will be randomly assigned to adjuvant treatment with 2mg of vitamin B12 (cobalamin).

Group Type: EXPERIMENTAL

Cobalamin

Intervention Type: DRUG

Adjuvant daily treatment with 2mg of cobalamin

Placebo oral tablet

15 subjects will be randomly assigned to adjuvant treatment with placebo.

Group Type: SHAM_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Adjuvant daily treatment with placebo

Interventions

Pyridoxine

Adjuvant daily treatment with 200mg of pyridoxine

Intervention Type: DRUG

Cobalamin

Adjuvant daily treatment with 2mg of cobalamin

Intervention Type: DRUG

Placebo Oral Tablet

Adjuvant daily treatment with placebo

Intervention Type: DRUG

Other Intervention Names

Vitamin B6; Vitamin B12

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lia LO Sanders, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Núcleo de Pesquisa e Desenvolvimento de Medicamentos

Locations

Núcleo de Pesquisa e Desenvolvimento de Medicamentos - UFC

Fortaleza, Ceará, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Lia LO Sanders, MD, PhD

Role: CONTACT

Phone: +55(85)3366-8338

Email: lia_sanders@hotmail.com

Facility Contacts

Lia LO Sanders, MD, PhD

Role: primary

Other Identifiers

B12B16study

Identifier Type: -

Identifier Source: org_study_id