SchizophreniaPhase 2/3NCT03790345
Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics
A Phase 2/3 study testing Pyridoxine and Cobalamin in people with Schizophrenia and Drug Induced Movement Disorder, Unspecified, run by Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara at 1 site in Brazil.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia, Drug Induced Movement Disorder, Unspecified, Oxidative Stress
- What is being tested?
- Pyridoxine and Cobalamin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteBrazil
- Study dates
- 3 Sep 2019to 3 Nov 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Núcleo de Pesquisa e Desenvolvimento de Medicamentos - UFC
Fortaleza, Ceará, 60430-275
Lia LO Sanders, MD, PhD
About this study
Official title: Effect of Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics
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.
Read the 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.
- Being tested
- Pyridoxine, Cobalamin, Placebo Oral Tablet
- Keywords
- Schizophrenia, Cobalamin, Pyridoxine, Drug-induced movement disorder
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyridoxineDrug
Also called Vitamin B6
Adjuvant daily treatment with 200mg of pyridoxine
CobalaminDrug
Also called Vitamin B12
Adjuvant daily treatment with 2mg of cobalamin
Placebo Oral TabletDrug
Adjuvant daily treatment with placebo
| Study group | Role | What they receive |
|---|---|---|
| Experimental group 1 | Experimental | 15 subjects will be randomly assigned to adjuvant treatment with 200mg of vitamin B6 (pyridoxine). Receives: Drug: Pyridoxine |
| Experimental group 2 | Experimental | 15 subjects will be randomly assigned to adjuvant treatment with 2mg of vitamin B12 (cobalamin). Receives: Drug: Cobalamin |
| Placebo oral tablet | Sham comparator | 15 subjects will be randomly assigned to adjuvant treatment with placebo. Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline and 12 weeks
Secondary outcomes (9)
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.
Measured: Baseline and 12 weeks
Change in Plasma Glutathione (GSH)
GSH in ng/mL
Measured: Baseline and 12 weeks
Change in serum level of Nitrite
Nitrite in nanomole/mililiter
Measured: Baseline and 12 weeks
Change in serum level of Thiobarbituric acid reactive substances (TBARS)
TBARS in mmol of malonaldehyde/mL
Measured: Baseline and 12 weeks
Change in serum level of Interleukin 1 β (IL-1β)
IL-1β in pg/mL
Measured: Baseline and 12 weeks
Change in serum level of Interleukin-4
IL-4 in pg/mL
Measured: Baseline and 12 weeks
Change in serum level of Interferon gamma (IFNγ)
IFNγ in pg/mL
Measured: Baseline and 12 weeks
Change in serum level of Tumor necrosis factor alpha (TNF-α)
TNF-α in pg/mL
Measured: Baseline and 12 weeks
Change in Indoleamine 2,3-dioxygenase (IDO) enzymatic activity
IDO activity in U IDO mol^-1/mg^-1
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2018
- Study start3 Sep 2019
- Primary completion3 Jun 2020 (estimated)
- Study completion3 Nov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Proof of concept 12-week prospective, randomized, double-blind, controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lia LO Sanders, MD, PhD, Principal investigator, Núcleo de Pesquisa e Desenvolvimento de Medicamentos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03790345
- Sponsor's protocol ID
- B12B16study
- Status last verified
- Dec 2018
- First submitted
- 21 Dec 2018
- Last updated
- 18 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics
- ClinicalTrials.gov ID
- NCT03790345
- Acronym / sponsor ID
- B12B16study
- Keywords
- Schizophrenia, Cobalamin, Pyridoxine, Drug-induced movement disorder
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do CearaUniversity, hospital or other
- Study start
- 3 Sep 2019 (actual)
- Primary completion
- 3 Jun 2020 (estimated)
- Study completion
- 3 Nov 2021 (estimated)
- First posted
- 31 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Proof of concept 12-week prospective, randomized, double-blind, controlled trial
| Arm | Type | Receives |
|---|---|---|
| Experimental group 1 | Experimental | Drug: Pyridoxine15 subjects will be randomly assigned to adjuvant treatment with 200mg of vitamin B6 (pyridoxine). |
| Experimental group 2 | Experimental | Drug: Cobalamin15 subjects will be randomly assigned to adjuvant treatment with 2mg of vitamin B12 (cobalamin). |
| Placebo oral tablet | Sham comparator | Drug: Placebo Oral Tablet15 subjects will be randomly assigned to adjuvant treatment with placebo. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PyridoxineAlso: Vitamin B6Adjuvant daily treatment with 200mg of pyridoxine | Drug | Experimental group 1 |
| CobalaminAlso: Vitamin B12Adjuvant daily treatment with 2mg of cobalamin | Drug | Experimental group 2 |
| Placebo Oral TabletAdjuvant daily treatment with placebo | Drug | Placebo oral tablet |
Primary outcome
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.
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.
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.
9 secondary outcomes
Change in the Brief Psychiatry Rating Scale (BPRS) scores
Time frame: Baseline and 12 weeks
Change in Plasma Glutathione (GSH)
Time frame: Baseline and 12 weeks
Change in serum level of Nitrite
Time frame: Baseline and 12 weeks
Change in serum level of Thiobarbituric acid reactive substances (TBARS)
Time frame: Baseline and 12 weeks
Change in serum level of Interleukin 1 β (IL-1β)
Time frame: Baseline and 12 weeks
Change in serum level of Interleukin-4
Time frame: Baseline and 12 weeks
Change in serum level of Interferon gamma (IFNγ)
Time frame: Baseline and 12 weeks
Change in serum level of Tumor necrosis factor alpha (TNF-α)
Time frame: Baseline and 12 weeks
Change in Indoleamine 2,3-dioxygenase (IDO) enzymatic activity
Time frame: Baseline and 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lia LO Sanders, MD, PhD principal investigator
Núcleo de Pesquisa e Desenvolvimento de Medicamentos
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Pyridoxine and Cobalamin in people with Schizophrenia and Drug Induced Movement Disorder, Unspecified, run by Nucleo De Pesquisa E Desenvolvimento De Medicamentos Da Universidade Federal Do Ceara at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lia LO Sanders, MD, PhD (+55(85)3366-8338, lia_sanders@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the Simpson-Angus Extrapyramidal Symptoms Scale (SAS) scores (time frame: Baseline and 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2019.