Pyridoxal Kinase Activity in Tardive Dyskinesia

Tardive Dyskinesia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01908452
• Other study ID #: LMRK0911
• Status: Withdrawn
• Phase: Phase 3
• First received: July 25, 2012
• Last updated: July 23, 2013
• Start date: July 2011
• Est. completion date: July 2011

Study information

• Verified date: July 2011
• Source: Beersheva Mental Health Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Dyskinesias
• Tardive Dyskinesia

Intervention

Drug:
• Pyridoxine
1200 mg/d during 12 weeks

Locations

Country	Name	City	State
Israel	Be'er Sheva Mental Health Center	Be'er Sheva
Israel	Sha'ar Menashe Mental Health Center	Hadera
Israel	Tirat Carmel Mental Health Center	Haifa

Sponsors (3)

Lead Sponsor	Collaborator
Beersheva Mental Health Center	Sha’ar Menashe Mental Health Center, Tirat Carmel Mental Health Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Extrapyramidal Symptom Rating Scale (ESRS)		participants will be followed for the duration of hospital stay every 2 weeks, an expected average of 8 weeks	Yes
Primary	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	Yes
Primary	Barnes Akathisia Scale		participants will be followed for the duration of hospital stay, every 2 weeks. an expected average of 8 weeks	No
Secondary	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	No