Neuroleptic-induced Tardive Dyskinesia Clinical Trial
Official title:
A Dual-centre, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Determine the Effects of Various Adjunctive Doses of Sarizotan in the Treatment of Patients With Neuroleptic-induced Tardive Dyskinesia
TD is a troublesome and potentially irreversible side effect associated with the use of
neuroleptics. While the newer neuroleptics are improved in this regard, they all still carry
the risk of TD.
The present study proposes that sarizotan is a potential agent for treating
neuroleptic-induced TD based on preliminary data indicating efficacy in the management of
dyskinesias associated with Parkinson's disease. Its efficacy is further substantiated by
pre-clinical data obtained from the vacuous chewing movement (VCM) model in rats, a model we
employ ourselves in investigating the relationship between D2 occupancy and TD. The present
study also examines the effects of sarizotan on cognitive function, given the association
between TD and cognitive deficits.
The primary objective of the study is to assess the safety and the anti-dyskinetic
properties of sarizotan at various dosages for neuroleptic-induced TD.
The secondary objective of the study is to assess the effects of sarizotan on cognitive
function in patients with neuroleptic-induced TD.
The diagnosis of neuroleptic-induced TD will be confirmed by history and physical
examination. Patients will be evaluated at baseline, 2, 4, 8, and 12 weeks. Safety will be
assessed by vital signs, ECG, routine blood tests, the ACTH stimulation test, and the
clinician's and patient's global impression of tolerability.
Procedures:
For efficacy, the primary outcome variable will be changes in the Abnormal Involuntary
Movement Scale (AIMS), and a baseline score of >3 ('moderate') will be required for item 8
(Severity of Abnormal Movements). Quantitative evaluation of movements will be carried out
in two ways. The first involves a series of instrumental and clinical measures that were
developed as a battery for the assessment of antipsychotic-induced parkinsonism and TD. The
second means of quantifying the movements involves the use of video recording, with
independent evaluation by several raters (Appendix I). Such approaches have gained
popularity in the quantification of movement disorders as a means of improving reliability.
Secondary measures will include the positive and negative syndrome scale (PANSS) and other
movement disorder scales (Simpson-Angus Rating Scales) for acute extrapyramidal symptoms
(EPS), and the Barnes Akathisia Rating Scale (BARS). Global impressions of efficacy and
tolerability by the clinician (CGI) and by the patients (PGI) will be recorded at all study
visits after the commencement of treatment. To assess potential cognitive changes that may
occur in conjunction with TD changes, a battery of neuropsychological tests will be carried
out at baseline and endpoint (see Appendix II). To assess the relationship with primary
negative symptoms such as the deficit syndrome, the total and sub-scales of the Positive and
Negative Syndrome Scale will be evaluated.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00621998 -
Risperidone and Olanzapine for the Schizophrenic Patients With Neuroleptic-Induced Tardive Dyskinesia
|
Phase 4 |