Pyridoxal Kinase Activity in Tardive Dyskinesia

NCT01908452 | Withdrawn Phase 3

• 1 other identifier: LMRK0911
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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.

Conditions

Tardive Dyskinesia

Keywords

Schizophrenia; pyridoxal kinase activity; plasma pyridoxal level

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• 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

Study Arms (2)

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

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

Drug: Pyridoxine

Interventions

Pyridoxine DRUG

1200 mg/d during 12 weeks

placebo; vitamin B6 (pyridoxine)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beersheva Mental Health Center: lead
• Sha'ar Menashe Mental Health Center: collaborator
• Tirat Carmel Mental Health Center: collaborator

Study Sites (3)

Be'er Sheva Mental Health Center

Beersheba, 84170, Israel

Location

Sha'ar Menashe Mental Health Center

Hadera, Israel

Location

Tirat Carmel Mental Health Center

Haifa, Israel

Location

MeSH Terms

Conditions

Tardive Dyskinesia; Schizophrenia

Interventions

Pyridoxine

Condition Hierarchy (Ancestors)

Dyskinesia, Drug-Induced; Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Vitamin B 6; Picolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: A/Professor, Head of department

Study Record Dates

• First Submitted: July 25, 2012
• First Posted: July 25, 2013
• Study Start: July 1, 2011
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 25, 2013

Record last verified: 2011-07

Locations

IL (3)