Pyridoxal Kinase Activity in Tardive Dyskinesia

Sponsor

Beersheva Mental Health Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01908452

Collaborator

Sha'ar Menashe Mental Health Center (Other), Tirat Carmel Mental Health Center (Other)

Enrollment

Locations

Arms

Patients Per Site

Study Details

Study Description

Brief 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.

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.

Condition or Disease	Intervention/Treatment	Phase
Tardive Dyskinesia	Drug: Pyridoxine	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

Pyridoxal Kinase Activity in Schizophrenia Patients Without Versus With Tardive Dyskinesia Treated With Vitamin B6

Study Start Date :

Jul 1, 2011

Actual Primary Completion Date :

Jul 1, 2011

Actual Study Completion Date :

Jul 1, 2011

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Extrapyramidal Symptom Rating Scale (ESRS) [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) [participants will be followed for the duration of hospital stay, every 2 weeks. an expected average of 8 weeks]
Barnes Akathisia Scale [participants will be followed for the duration of hospital stay, every 2 weeks. an expected average of 8 weeks]

Secondary Outcome Measures

The Positive and Negative Syndrome Scale (PANSS) [participants will be followed for the duration of hospital stay, twice during hospitalization. an expected average of 8 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.