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

NCT03790345 | Unknown Phase 2

• 1 other identifier: B12B16study
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Drug Induced Movement Disorder, Unspecified; Oxidative Stress

Keywords

Schizophrenia; Cobalamin; Pyridoxine; Drug-induced movement disorder

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (9)

• Change in the Brief Psychiatry Rating Scale (BPRS) scores

  Baseline and 12 weeks

• Change in Plasma Glutathione (GSH)

  Baseline and 12 weeks

• Change in serum level of Nitrite

  Baseline and 12 weeks

• Change in serum level of Thiobarbituric acid reactive substances (TBARS)

  Baseline and 12 weeks

• Change in serum level of Interleukin 1 β (IL-1β)

  Baseline and 12 weeks

Study Arms (3)

Experimental group 1

EXPERIMENTAL

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

Drug: Pyridoxine

Experimental group 2

EXPERIMENTAL

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

Drug: Cobalamin

Placebo oral tablet

SHAM COMPARATOR

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

Drug: Placebo Oral Tablet

Interventions

Pyridoxine DRUG

Adjuvant daily treatment with 200mg of pyridoxine

Also known as: Vitamin B6

Experimental group 1

Cobalamin DRUG

Adjuvant daily treatment with 2mg of cobalamin

Also known as: Vitamin B12

Experimental group 2

Placebo Oral Tablet DRUG

Adjuvant daily treatment with placebo

Placebo oral tablet

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara: lead

Study Sites (1)

Núcleo de Pesquisa e Desenvolvimento de Medicamentos - UFC

Fortaleza, Ceará, 60430-275, Brazil

RECRUITING

MeSH Terms

Conditions

Schizophrenia

Interventions

Pyridoxine; Vitamin B 6; Vitamin B 12

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Picolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Lia LO Sanders, MD, PhD

  Núcleo de Pesquisa e Desenvolvimento de Medicamentos

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lia LO Sanders, MD, PhD

CONTACT

+55(85)3366-8338; lia_sanders@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Proof of concept 12-week prospective, randomized, double-blind, controlled trial

Study Record Dates

• First Submitted: December 21, 2018
• First Posted: December 31, 2018
• Study Start: September 3, 2019
• Primary Completion: June 3, 2020
• Study Completion: November 3, 2021
• Last Updated: December 18, 2019

Record last verified: 2018-12

Locations

BR (1)