Antipsychotic Augmentation With L-Dopa
Information source: Centre for Addiction and Mental Health
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia
Intervention: levodopa/carbidopa (generic version of Sinemet) (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Centre for Addiction and Mental Health Official(s) and/or principal investigator(s): Gary Remington, MD PhD FRCPC, Principal Investigator, Affiliation: Centre for Addiction and Mental Health
Overall contact: George Foussias, MD PhD FRCPC, Phone: 416-535-8501, Ext: 34390, Email: george_foussias@camh.net
Summary
Dopamine, a chemical in the brain, has been linked to schizophrenia for a number of years.
More recently, there is evidence that certain areas affected in schizophrenia (e. g.
motivation, cognition) may reflect too little dopamine, whereas symptoms like hallucinations
and delusions have been linked to too much dopamine.
This study is designed to evaluate the safety, tolerability, and efficacy of giving L-dopa
(Sinemet) to see if it will improve those symptoms related to too little dopamine. L-dopa
has been approved for other medical conditions (e. g. Parkinson's disease) and works to
increase levels of dopamine.
The investigators are linking this study with neuroimaging (fMRI) which will allows us to
link any changes the investigators might find in clinical symptoms with changes in the
brain. This information can prove useful in better understanding the mechanisms that account
for these symptoms, as well as possible new treatments.
At present , treatments for these other symptoms that seem important in functional measures
of outcome (i. e. deficit symptoms, including amotivation; cognitive symptoms) in
schizophrenia have not proven particularly effective. It is hoped that L-dopa may provide a
treatment that is more effective; going forward, this information would also be useful in
drug development and future lines of investigation.
1. L-dopa will prove effective in improving deficit (also called 'primary negative' e. g.
amotivation) and cognitive symptoms in schizophrenia.
2. It will be well tolerated and not increase risk of psychotic symptoms when administered
in conjunction with their regular antipsychotic medications.
Clinical Details
Official title: Augmentation of Antipsychotics With L-Dopa (Sinemet)
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: SANS - Schedule for the Assessment of Negative Symptoms
Secondary outcome: MATRICS-Consensus Cognitive BatteryBPRS - Brief Psychotic Rating Scale SAPS - Schedule for the Assessment of Positive Symptoms NIMH-MATRICS Brief Negative Symptoms Scale CGI-S - Clinical Global Impression - Severity Scale QLS - Quality of Life Scale CDS - Calgary Depression Scale SAS - Simpson Angus Scale for Extrapyramidal Symptoms BARS - Barnes Akathisia Rating Scales AIMS - Abnormal Involuntary Movement Scale UKU - Udvalg for Kliniske Undersogelses LUNSERS - Liverpool University Neuroleptic Side-Effect Rating Scale BIS-11 - Barrett Impulsivity Scale Y-BOCS - Yale-Brown Obsessive Compulsive Scale DAI - Drug Attitude Inventory fMRI - Functional Magnetic Resonance Imaging SWN - Subjective Well-Being on Neuroleptics Scale
Detailed description:
Pharmacological (and non-pharmacological) strategies that may significantly improve the
negative and cognitive symptoms of schizophrenia represent a critical unmet therapeutic
need. There is wide acceptance of the notion that both negative and cognitive symptoms are
best understood as features of hypo- rather than hyperdopaminergic activity. The primary
negative and cognitive symptoms appear central to schizophrenia and predate the
neurodevelopmental changes that subsequently give rise to the hyperdopaminergic state
underlying positive symptoms. In using L-Dopa specifically, we avoid the abuse potential of
agents such as the psychostimulants, or perturbations in pharmacological action as a
function of dose, as observed with dopamine agonists. Further, more recent neuroimaging
studies have provided in vivo evidence in keeping with the underlying rationale. First,
imaging studies have demonstrated that L-dopa induces shifts in activity in both cortical
and subcortical structures linked to reward, affect and cognition. Along similar lines,
L-dopa-induced changes have been associated with improvement in motivation, cognitive tasks,
and affect.
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- SCID-confirmed (Structured Clinical Interview for DSM-IV Axis I Disorders) diagnosis
of schizophrenia
- ages 18-55
Exclusion Criteria:
- history of substance abuse or dependence within 3 months; (ii) positive urine drug
screen
- history or evidence of any disorder that might adversely influence cognitive measures
(e. g. mental retardation)
- presence of serious neurological or general medical condition (e. g., Parkinson's
disease, cardiac arrhythmia, epilepsy)
- clinical or laboratory evidence of uncompensated cardiovascular, endocrine,
hematologic, hepatic, pulmonary (including bronchial asthma), or renal disease,
narrow-angle glaucoma, malignant melanoma
- pregnancy/nursing or women of child-bearing age not on regular contraceptive therapy
(effects of L-dopa unknown)
Locations and Contacts
George Foussias, MD PhD FRCPC, Phone: 416-535-8501, Ext: 34390, Email: george_foussias@camh.net
Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada; Recruiting Gary Remington, MD PhD FRCPC, Principal Investigator George Foussias, MD PhD FRCPC, Sub-Investigator Naren Rao, MD, Sub-Investigator Romina Mizrahi, MD; PhD, Sub-Investigator
Additional Information
Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital. It is fully affiliated with the University of Toronto, and is a PAHO/WHO Collaborating Centre.
Starting date: September 2012
Last updated: March 9, 2015
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