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Trial record 11 of 230 for:    pyridoxine

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

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ClinicalTrials.gov Identifier: NCT03790345
Recruitment Status : Not yet recruiting
First Posted : December 31, 2018
Last Update Posted : December 31, 2018
Sponsor:
Information provided by (Responsible Party):
Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara

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 or schizoaffective disorder who present with tardive dyskinesia, dystonia and parkinsonism.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug Induced Movement Disorder, Unspecified Oxidative Stress Drug: Pyridoxine Drug: Cobalamin Drug: Placebo Oral Tablet Phase 2 Phase 3

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. 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 and schizoaffective 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. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Proof of concept 12-week prospective, randomized, double-blind, controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics
Estimated Study Start Date : January 3, 2019
Estimated Primary Completion Date : January 3, 2020
Estimated Study Completion Date : January 3, 2021


Arm Intervention/treatment
Experimental: Experimental group 1
15 subjects will be randomly assigned to adjuvant treatment with 200mg of vitamin B6 (pyridoxine).
Drug: Pyridoxine
Adjuvant daily treatment with 200mg of pyridoxine
Other Name: Vitamin B6

Experimental: Experimental group 2
15 subjects will be randomly assigned to adjuvant treatment with 2mg of vitamin B12 (cobalamin).
Drug: Cobalamin
Adjuvant daily treatment with 2mg of cobalamin
Other Name: Vitamin B12

Sham Comparator: Placebo oral tablet
15 subjects will be randomly assigned to adjuvant treatment with placebo.
Drug: Placebo Oral Tablet
Adjuvant daily treatment with placebo




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. Change in Plasma Glutathione (GSH) [ Time Frame: Baseline and 12 weeks ]
    GSH in ng/mL

  3. Change in serum level of Nitrite [ Time Frame: Baseline and 12 weeks ]
    Nitrite in nanomole/mililiter

  4. Change in serum level of Thiobarbituric acid reactive substances (TBARS) [ Time Frame: Baseline and 12 weeks ]
    TBARS in mmol of malonaldehyde/mL

  5. Change in serum level of Interleukin 1 β (IL-1β) [ Time Frame: Baseline and 12 weeks ]
    IL-1β in pg/mL

  6. Change in serum level of Interleukin-4 [ Time Frame: Baseline and 12 weeks ]
    IL-4 in pg/mL

  7. Change in serum level of Interferon gamma (IFNγ) [ Time Frame: Baseline and 12 weeks ]
    IFNγ in pg/mL

  8. Change in serum level of Tumor necrosis factor alpha (TNF-α) [ Time Frame: Baseline and 12 weeks ]
    TNF-α in pg/mL

  9. Change in Indoleamine 2,3-dioxygenase (IDO) enzymatic activity [ Time Frame: Baseline and 12 weeks ]
    IDO activity in U IDO mol^-1/mg^-1



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03790345


Contacts
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Contact: Lia LO Sanders, MD, PhD +55(85)3366-8338 lia_sanders@hotmail.com

Locations
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Brazil
Núcleo de Pesquisa e Desenvolvimento de Medicamentos - UFC
Fortaleza, CE, Brazil, 60430-275
Sponsors and Collaborators
Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara
Investigators
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Principal Investigator: Lia LO Sanders, MD, PhD Núcleo de Pesquisa e Desenvolvimento de Medicamentos

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Responsible Party: Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara
ClinicalTrials.gov Identifier: NCT03790345     History of Changes
Other Study ID Numbers: B12B16study
First Posted: December 31, 2018    Key Record Dates
Last Update Posted: December 31, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara:
Schizophrenia
Cobalamin
Pyridoxine
Drug-induced movement disorder
Additional relevant MeSH terms:
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Vitamin B 6
Pyridoxal
Pyridoxine
Movement Disorders
Disease
Schizophrenia
Pathologic Processes
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Central Nervous System Diseases
Nervous System Diseases
Vitamins
Vitamin B 12
Hydroxocobalamin
Vitamin B Complex
Antipsychotic Agents
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Hematinics