Adjuvant Therapy With Pergolide in Treating Cognitive Deficits in Schizophrenia
Summary
The objective of this study is to compare the modulation of pergolide, a D1/D2 receptor agonist, to placebo in non-acute schizophrenic subjects under concomitant therapy with atypical antipsychotics on specific PFC functions. Further aims are to assess the influence of pergolide on psychopathology and extrapyramidal symptoms in comparison to placebo.
Description
Additionally to the desired treatment of positive symptoms, the administration of typical neuroleptics can lead to undesired side effects such as increase of negative symptomatic and cognitive deficits. The influence of atypical neuroleptics on cognition is still not very well studied. Furthermore there is evidence that some cognitive symptoms seen in schizophrenia are related to a disturbance in the prefrontal cortex PFC and involve specific subtypes of dopamine receptors, namely D1 subtypes, which predominates in this area. It is assumed that patients with this spectrum of cognitive deficits have the worse course and prognosis. Furthermore these deficits are more therapy resistant to the conventional current therapy approaches. There is however some evidence pointing to a positive influence of dopamine agonists on these deficits, but the selective effect of dopamine sub-receptors is still not well investigated. The aim of the study is to examine whether cognitive deficits in higher cognitive functions of the PFC such as working memory, semantic association and executive control improves under dopamine agonistic therapy in schizophrenia and whether this is related to selective D1 modulation.
We predict that the modulation of D1 subtype receptors improve performance in each of these tasks. Because there is no D1 agonist available for human research we decided to use a design comparing a dopamine agonist with mixed D1 and D2 agonistic properties (pergolide) to placebo under a stable D2 antagonistic continuous-therapy with atypical antipsychotics. With this design the D2-component of pergolide can be antagonized by the atypical antipsychotics and a D1 agonistic effect can be suggested, as well as protecting patients against a psychotic re-exacerbation. With this study we aim to bring more insight in the therapy of PFC cognitive deficits of schizophrenia by helping to elucidate the role of selective agonists on cognition in schizophrenic patients. I
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
Conditions
Schizophrenia
Intervention
Pergolide
Location
Zentralinstitut für Seelische Gesundheit
Mannheim
68159
Germany
69115
Status
Completed
Source
University of Heidelberg
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01066403
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Schizophrenia, Paranoid
A chronic form of schizophrenia characterized primarily by the presence of persecutory or grandiose delusions, often associated with hallucination.
Schizophrenia, Catatonic
A type of schizophrenia characterized by abnormality of motor behavior which may involve particular forms of stupor, rigidity, excitement or inappropriate posture.
Schizophrenia, Childhood
An obsolete concept, historically used for childhood mental disorders thought to be a form of schizophrenia.
Pergolide
A long-acting dopamine agonist which has been used to treat PARKINSON DISEASE and HYPERPROLACTINEMIA but withdrawn from some markets due to potential for HEART VALVE DISEASES.
Schizophrenia, Disorganized
A type of schizophrenia characterized by frequent incoherence; marked loosening of associations, or grossly disorganized behavior and flat or grossly inappropriate affect that does not meet the criteria for the catatonic type; associated features include extreme social withdrawal, grimacing, mannerisms, mirror gazing, inappropriate giggling, and other odd behavior. (Dorland, 27th ed)
Clinical Trials
Randomized Study of Pergolide in Children With Tourette Syndrome
OBJECTIVES: I. Evaluate the presumed mechanism of action of low dose pergolide to act acutely through the dopaminergic autoreceptor or postsynaptically at D2 sites in children 7 to 17 wi...
Pergolide Treatment for Substance Abusers - 4
The purpose of this study is to evaluate the safety and efficacy of pergolide for cocaine dependence.
Pergolide for Cognitive Symptoms in Schizotypal Personality Disorder
Hypothesis: Schizotypal personality disorder patients will show cognitive improvements in 1) working memory 2) learning and memory 3) sustained attention 4) enhanced performance on the AX-...
Compassionate Use Study of Pergolide in Patients With Parkinson's Disease
This compassionate use study is designed to monitor safety in patients who have been doing well on pergolide therapy, wish to continue treatment, and have not been able to tolerate alterna...
Dose Response Trial of Pergolide for Cocaine Dependence - 1
The purpose of this study is to evaluate the efficacy and safety of pergolide for treatment of cocaine dependence.
PubMed Articles
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One of the most widely used animal models of Parkinson's disease (PD) involves injecting 6-hydroxydopamine (6-OHDA) directly into the substantia nigra (SN). Some recent reports speculated that dopamin...
Psychostimulant abuse represents a psychiatric disorder and societal concern that has been largely unamenable to therapeutic interventions. We have previously demonstrated that the 5-HT₃ antagonist...
Resting EEG deficits in accused murderers with schizophrenia.
Empirical evidence continues to suggest a biologically distinct violent subtype of schizophrenia. The present study examined whether murderers with schizophrenia would demonstrate resting EEG deficits...
