Antipsychotic Augmentation With L-Dopa

Overview

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.

Full Title of Study: “Augmentation of Antipsychotics With L-Dopa (Sinemet)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2015

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.

Interventions

  • Drug: levodopa/carbidopa (generic version of Sinemet)
    • Oral levodopa 900mg daily as tolerated.

Arms, Groups and Cohorts

  • Experimental: L-Dopa (Sinemet)
    • Augmentation of current antipsychotic treatment with oral L-Dopa (levodopa/carbidopa) up to 900mg daily for 8 weeks

Clinical Trial Outcome Measures

Primary Measures

  • SANS – Schedule for the Assessment of Negative Symptoms
    • Time Frame: 8 weeks

Secondary Measures

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

Participating in This Clinical Trial

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)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Centre for Addiction and Mental Health
  • Provider of Information About this Clinical Study
    • Principal Investigator: George Foussias, Sub-Investigator – Centre for Addiction and Mental Health
  • Overall Official(s)
    • Gary Remington, MD PhD FRCPC, Principal Investigator, Centre for Addiction and Mental Health

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.