Pyridoxal Kinase Activity in Tardive Dyskinesia

July 23, 2013 updated by: Vladimir Lerner, Beersheva Mental Health Center

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.

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 Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Be'er Sheva, Israel, 84170
        • Be'er Sheva Mental Health Center
      • Hadera, Israel
        • Sha'ar Menashe Mental Health Center
      • Haifa, Israel
        • Tirat Carmel Mental Health Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: vitamin B6 (pyridoxine)
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
Drug: Pyridoxine
1200 mg/d during 12 weeks
Placebo Comparator: placebo
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
Drug: Pyridoxine
1200 mg/d during 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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
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
participants will be followed for the duration of hospital stay, every 2 weeks. an expected average of 8 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
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
participants will be followed for the duration of hospital stay, twice during hospitalization. an expected average of 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beersheva Mental Health Center

Collaborators

Tirat Carmel Mental Health Center
Sha'ar Menashe Mental Health Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

July 25, 2012

First Submitted That Met QC Criteria

July 23, 2013

First Posted (Estimate)

July 25, 2013

Study Record Updates

Last Update Posted (Estimate)

July 25, 2013

Last Update Submitted That Met QC Criteria

July 23, 2013

Last Verified

July 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LMRK0911

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Tardive Dyskinesia

Clinical Trials on Pyridoxine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Chile

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe