Antipsychotic Augmentation With L-Dopa

Phase 2

Completed

• Conditions: Schizophrenia
• Interventions: Drug: levodopa/carbidopa (generic version of Sinemet)

• Registration Number: NCT01636037
• Lead Sponsor: Centre for Addiction and Mental Health

Brief 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.

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.

Study Timeline

• Study First Submitted: 2012-07-05
• Study First Submitted QC: 2012-07-09
• Study First Posted: 2012-07-10
• Study Start: 2012-09
• Primary Completion: 2015-12
• Study Completion: 2016-01
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-11
• Last Update Posted: 2016-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
L-Dopa (Sinemet)	levodopa/carbidopa (generic version of Sinemet)	Augmentation of current antipsychotic treatment with oral L-Dopa (levodopa/carbidopa) up to 900mg daily for 8 weeks

Primary Outcome Measures

Name	Time	Method
SANS - Schedule for the Assessment of Negative Symptoms	8 weeks

Secondary Outcome Measures

Name	Time	Method
LUNSERS - Liverpool University Neuroleptic Side-Effect Rating Scale	8 weeks
Y-BOCS - Yale-Brown Obsessive Compulsive Scale	8 weeks
DAI - Drug Attitude Inventory	8 weeks
UKU - Udvalg for Kliniske Undersogelses	8 weeks	Measures General Side Effects
SAPS - Schedule for the Assessment of Positive Symptoms	8 weeks
NIMH-MATRICS Brief Negative Symptoms Scale	8 weeks
BIS-11 - Barrett Impulsivity Scale	8 weeks
AIMS - Abnormal Involuntary Movement Scale	8 weeks
SAS - Simpson Angus Scale for Extrapyramidal Symptoms	8 weeks
CGI-S - Clinical Global Impression - Severity Scale	8 weeks
QLS - Quality of Life Scale	8 weeks
CDS - Calgary Depression Scale	8 weeks
BPRS - Brief Psychotic Rating Scale	8 weeks
fMRI - Functional Magnetic Resonance Imaging	8 weeks	Changes in Regional Brain Activity
MATRICS-Consensus Cognitive Battery	8 weeks
BARS - Barnes Akathisia Rating Scales	8 weeks
SWN - Subjective Well-Being on Neuroleptics Scale	8 weeks

Trial Locations

Locations (1)

Centre for Addiction and Mental Health; 🇨🇦 Toronto, Ontario, Canada