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Pyridoxal Kinase Activity in Tardive Dyskinesia

This study has been withdrawn prior to enrollment.
(Not funded)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01908452
First Posted: July 25, 2013
Last Update Posted: July 25, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Sha’ar Menashe Mental Health Center
Tirat Carmel Mental Health Center
Information provided by (Responsible Party):
Vladimir Lerner, Beersheva Mental Health Center
  Purpose

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 Intervention Phase
Tardive Dyskinesia Drug: Pyridoxine Phase 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Vladimir Lerner, Beersheva Mental Health Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 0
Study Start Date: July 2011
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01908452


Locations
Israel
Be'er Sheva Mental Health Center
Be'er Sheva, Israel, 84170
Sha'ar Menashe Mental Health Center
Hadera, Israel
Tirat Carmel Mental Health Center
Haifa, Israel
Sponsors and Collaborators
Beersheva Mental Health Center
Sha’ar Menashe Mental Health Center
Tirat Carmel Mental Health Center
  More Information

Responsible Party: Vladimir Lerner, A/Professor, Head of department, Beersheva Mental Health Center
ClinicalTrials.gov Identifier: NCT01908452     History of Changes
Other Study ID Numbers: LMRK0911
First Submitted: July 25, 2012
First Posted: July 25, 2013
Last Update Posted: July 25, 2013
Last Verified: July 2011

Keywords provided by Vladimir Lerner, Beersheva Mental Health Center:
Schizophrenia
pyridoxal kinase activity
plasma pyridoxal level

Additional relevant MeSH terms:
Dyskinesias
Tardive Dyskinesia
Dyskinesia, Drug-Induced
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Vitamins
Vitamin B 6
Pyridoxal
Pyridoxine
Vitamin B Complex
Micronutrients
Growth Substances
Physiological Effects of Drugs