Tardive DyskinesiaPhase 3NCT01908452
Pyridoxal Kinase Activity in Tardive Dyskinesia
A Phase 3 study testing Pyridoxine in people with Tardive Dyskinesia, run by Beersheva Mental Health Center at 3 sites in Israel.
Trial summary
Objectives: The mechanisms of tardive dyskinesia (TD) remain unclear, although pathophysiologic theories have proposed mechanisms such as dopamine receptor supersensitivity, the degeneration of cholinergic striatal interneurons, γ-aminobutyric acid (GABA) depletion, and an excess of free radicals. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tardive Dyskinesia
- What is being tested?
- Pyridoxine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 3 sitesIsrael
- Study dates
- Jul 2011to Jul 2011
- Phase
- Phase 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Inpatients
- DSM-IV diagnosis of schizophrenia or schizoaffective disorder with and without tardive dyskinesia (TD)
- Total ESRS score should be more than 20 in subjects with TD
- Ability to provide a written informed consent
Who cannot join
- Patients with concurrent medical illness or any movement disorder resemble TD
- Patients who received any vitamin medication
- Evidence of substance or alcohol abuse or a family history of movement disorder.
- Pregnancy and/or lactation.
Trial locations and contacts
3 sites in 1 country.
Israel3 sites
Be'er Sheva Mental Health Center
Beersheba, 84170
Sha'ar Menashe Mental Health Center
Hadera
Tirat Carmel Mental Health Center
Haifa
About this study
Official title: Pyridoxal Kinase Activity in Schizophrenia Patients Without Versus With Tardive Dyskinesia Treated With Vitamin B6
Objectives: The mechanisms of tardive dyskinesia (TD) remain unclear, although pathophysiologic theories have proposed mechanisms such as dopamine receptor supersensitivity, the degeneration of cholinergic striatal interneurons, γ-aminobutyric acid (GABA) depletion, and an excess of free radicals.
Prior development of second generation antipsychotic agents, tardive movement disorders were widespread among neuroleptics treated patients. There were great expectations of the new novel drugs. Unfortunately, reports about tardive movement disturbances induced by these medications became more and more frequent, although it has been in use for less than two decades.
Read more
A recent study demonstrated that schizophrenic and schizoaffective patients suffering from TD had the mean level of pyridoxal 5'-phosphate (PLP) below lower limit of normal range, while those patients without TD had normal values. At the same time, some open and double-blind placebo-controlled, randomized clinical studies showed that vitamin B6 was very effective in treatment of TD.
Pyridoxal kinase is a key enzyme for the biosynthesis of PLP, the biologically active form of vitamin B6. Some publications reported that the finding of high vitamin B6 levels is consistent with recent reports of low levels of PLP and low activity of pyridoxal kinase. It may explain the functional need for high-dose vitamin B6 supplementation in subjects with TD.
Methods: A multicenter study including 300 schizophrenia and schizoaffective subjects will be performed. The trial will be consisted of 2 parts: the first part a single comparison pyridoxal kinase plasma activity in patients with and without TD; in the second part only TD schizophrenia and schizoaffective patients will continue. It will be a 12-week, randomized, double-blind placebo-controlled trial. Vitamin B6 (1200 mg/day) or placebo capsules will be added to the stable ongoing antipsychotic treatment of 150 schizophrenia patients. Participants will be assessed at baseline and after every 2 weeks of treatment till week 12. Pyridoxal kinase activity will be compared between patients who positively respond to vitamin B6 versus non responders. In addition, PLP levels will be monitored at baseline and at the end of the study.
A battery of research tools will be used for assessment of movement disorders, psychopathology, and side effects. The study will be performed along a period of 2 years.
- Conditions
- Tardive Dyskinesia
- Being tested
- Pyridoxine
- Keywords
- Schizophrenia, pyridoxal kinase activity, plasma pyridoxal level
- Medical subject headings
- Tardive Dyskinesia, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyridoxineDrug
1200 mg/d during 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| vitamin B6 (pyridoxine) | Experimental | The 150 participating subjects will be randomized into 2 groups: 75 patients will receive vitamin B6 (1200 mg/day) and 75 patients will receive placebo, each for 12 weeks in a double-blind mode Receives: Drug: Pyridoxine |
| placebo | Placebo comparator | The 150 participating subjects will be randomized into 2 groups: 75 patients will receive vitamin B6 (1200 mg/day) and 75 patients will receive placebo, each for 12 weeks in a double-blind mode Receives: Drug: Pyridoxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extrapyramidal Symptom Rating Scale (ESRS)
Measured: participants will be followed for the duration of hospital stay every 2 weeks, an expected average of 8 weeks
The Clinical Global Impression Scale (CGI)
Measured: participants will be followed for the duration of hospital stay, every 2 weeks. an expected average of 8 weeks
Barnes Akathisia Scale
Measured: participants will be followed for the duration of hospital stay, every 2 weeks. an expected average of 8 weeks
Secondary outcomes (1)
The Positive and Negative Syndrome Scale (PANSS)
Measured: participants will be followed for the duration of hospital stay, twice during hospitalization. an expected average of 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2013 (estimated)
- Study startJul 2011
- Primary completionJul 2011
- Study completionJul 2011
Why it stopped: Not funded
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tardive DyskinesiaStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beersheva Mental Health Center
- Sponsor type
- Other government
- Collaborators
- Sha'ar Menashe Mental Health Center, Tirat Carmel Mental Health Center
- Responsible party
- Principal investigator, Vladimir Lerner, Beersheva Mental Health Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01908452
- Sponsor's protocol ID
- LMRK0911
- Status last verified
- Jul 2011
- First submitted
- 25 Jul 2012
- Last updated
- 25 Jul 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pyridoxal Kinase Activity in Schizophrenia Patients Without Versus With Tardive Dyskinesia Treated With Vitamin B6
- ClinicalTrials.gov ID
- NCT01908452
- Acronym / sponsor ID
- LMRK0911
- Conditions
- Tardive Dyskinesia
- Keywords
- Schizophrenia, pyridoxal kinase activity, plasma pyridoxal level
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Not funded
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Beersheva Mental Health CenterOther government
- Collaborators
- Sha'ar Menashe Mental Health Center, Tirat Carmel Mental Health Center
- Study start
- Jul 2011
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 25 Jul 2013 (estimated)
- 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.
Objectives: The mechanisms of tardive dyskinesia (TD) remain unclear, although pathophysiologic theories have proposed mechanisms such as dopamine receptor supersensitivity, the degeneration of cholinergic striatal interneurons, γ-aminobutyric acid (GABA) depletion, and an excess of free radicals.
Prior development of second generation antipsychotic agents, tardive movement disorders were widespread among neuroleptics treated patients. There were great expectations of the new novel drugs. Unfortunately, reports about tardive movement disturbances induced by these medications became more and more frequent, although it has been in use for less than two decades.
A recent study demonstrated that schizophrenic and schizoaffective patients suffering from TD had the mean level of pyridoxal 5'-phosphate (PLP) below lower limit of normal range, while those patients without TD had normal values. At the same time, some open and double-blind placebo-controlled, randomized clinical studies showed that vitamin B6 was very effective in treatment of TD.
Pyridoxal kinase is a key enzyme for the biosynthesis of PLP, the biologically active form of vitamin B6. Some publications reported that the finding of high vitamin B6 levels is consistent with recent reports of low levels of PLP and low activity of pyridoxal kinase. It may explain the functional need for high-dose vitamin B6 supplementation in subjects with TD.
Methods: A multicenter study including 300 schizophrenia and schizoaffective subjects will be performed. The trial will be consisted of 2 parts: the first part a single comparison pyridoxal kinase plasma activity in patients with and without TD; in the second part only TD schizophrenia and schizoaffective patients will continue. It will be a 12-week, randomized, double-blind placebo-controlled trial. Vitamin B6 (1200 mg/day) or placebo capsules will be added to the stable ongoing antipsychotic treatment of 150 schizophrenia patients. Participants will be assessed at baseline and after every 2 weeks of treatment till week 12. Pyridoxal kinase activity will be compared between patients who positively respond to vitamin B6 versus non responders. In addition, PLP levels will be monitored at baseline and at the end of the study.
A battery of research tools will be used for assessment of movement disorders, psychopathology, and side effects. The study will be performed along a period of 2 years.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| vitamin B6 (pyridoxine) | Experimental | Drug: PyridoxineThe 150 participating subjects will be randomized into 2 groups: 75 patients will receive vitamin B6 (1200 mg/day) and 75 patients will receive placebo, each for 12 weeks in a double-blind mode |
| placebo | Placebo comparator | Drug: PyridoxineThe 150 participating subjects will be randomized into 2 groups: 75 patients will receive vitamin B6 (1200 mg/day) and 75 patients will receive placebo, each for 12 weeks in a double-blind mode |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Inpatients
- DSM-IV diagnosis of schizophrenia or schizoaffective disorder with and without tardive dyskinesia (TD)
- Total ESRS score should be more than 20 in subjects with TD
- Ability to provide a written informed consent
Key exclusion criteria (4 listed)
- Patients with concurrent medical illness or any movement disorder resemble TD
- Patients who received any vitamin medication
- Evidence of substance or alcohol abuse or a family history of movement disorder.
- Pregnancy and/or lactation.
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 |
|---|---|---|
| Pyridoxine1200 mg/d during 12 weeks | Drug | placebo, vitamin B6 (pyridoxine) |
Primary outcome
Extrapyramidal Symptom Rating Scale (ESRS)
Time frame: participants will be followed for the duration of hospital stay every 2 weeks, an expected average of 8 weeks
The Clinical Global Impression Scale (CGI)
Time frame: participants will be followed for the duration of hospital stay, every 2 weeks. an expected average of 8 weeks
Barnes Akathisia Scale
Time frame: participants will be followed for the duration of hospital stay, every 2 weeks. an expected average of 8 weeks
1 secondary outcome
The Positive and Negative Syndrome Scale (PANSS)
Time frame: participants will be followed for the duration of hospital stay, twice during hospitalization. an expected average of 8 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2013.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pyridoxine in people with Tardive Dyskinesia, run by Beersheva Mental Health Center at 3 sites in Israel.
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 4 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: withdrawn, as of the sponsor's last update on 25 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Israel. 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 phase mean?
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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Extrapyramidal Symptom Rating Scale (ESRS) (time frame: participants will be followed for the duration of hospital stay every 2 weeks, an expected average of 8 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 25 Jul 2013.