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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 Battery

BPRS - 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

Page last updated: August 23, 2015

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