Antipsychotic Augmentation With L-Dopa

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01636037
Recruitment Status : Completed
First Posted : July 10, 2012
Last Update Posted : March 15, 2016
Information provided by (Responsible Party):
George Foussias, 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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: levodopa/carbidopa (generic version of Sinemet) Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Augmentation of Antipsychotics With L-Dopa (Sinemet)
Study Start Date : September 2012
Actual Primary Completion Date : December 2015
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: L-Dopa (Sinemet)
Augmentation of current antipsychotic treatment with oral L-Dopa (levodopa/carbidopa) up to 900mg daily for 8 weeks
Drug: levodopa/carbidopa (generic version of Sinemet)
Oral levodopa 900mg daily as tolerated.
Other Names:
  • Levodopa/carbidopa
  • Sinemet

Primary Outcome Measures :
  1. SANS - Schedule for the Assessment of Negative Symptoms [ Time Frame: 8 weeks ]

Secondary Outcome Measures :
  1. MATRICS-Consensus Cognitive Battery [ Time Frame: 8 weeks ]
  2. BPRS - Brief Psychotic Rating Scale [ Time Frame: 8 weeks ]
  3. SAPS - Schedule for the Assessment of Positive Symptoms [ Time Frame: 8 weeks ]
  4. NIMH-MATRICS Brief Negative Symptoms Scale [ Time Frame: 8 weeks ]
  5. CGI-S - Clinical Global Impression - Severity Scale [ Time Frame: 8 weeks ]
  6. QLS - Quality of Life Scale [ Time Frame: 8 weeks ]
  7. CDS - Calgary Depression Scale [ Time Frame: 8 weeks ]
  8. SAS - Simpson Angus Scale for Extrapyramidal Symptoms [ Time Frame: 8 weeks ]
  9. BARS - Barnes Akathisia Rating Scales [ Time Frame: 8 weeks ]
  10. AIMS - Abnormal Involuntary Movement Scale [ Time Frame: 8 weeks ]
  11. UKU - Udvalg for Kliniske Undersogelses [ Time Frame: 8 weeks ]
    Measures General Side Effects

  12. LUNSERS - Liverpool University Neuroleptic Side-Effect Rating Scale [ Time Frame: 8 weeks ]
  13. BIS-11 - Barrett Impulsivity Scale [ Time Frame: 8 weeks ]
  14. Y-BOCS - Yale-Brown Obsessive Compulsive Scale [ Time Frame: 8 weeks ]
  15. DAI - Drug Attitude Inventory [ Time Frame: 8 weeks ]
  16. fMRI - Functional Magnetic Resonance Imaging [ Time Frame: 8 weeks ]
    Changes in Regional Brain Activity

  17. SWN - Subjective Well-Being on Neuroleptics Scale [ Time Frame: 8 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01636037

Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5T 1R8
Sponsors and Collaborators
Centre for Addiction and Mental Health
Principal Investigator: Gary Remington, MD PhD FRCPC Centre for Addiction and Mental Health

Additional Information:
Responsible Party: George Foussias, Sub-Investigator, Centre for Addiction and Mental Health Identifier: NCT01636037     History of Changes
Other Study ID Numbers: 156/2011
First Posted: July 10, 2012    Key Record Dates
Last Update Posted: March 15, 2016
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by George Foussias, Centre for Addiction and Mental Health:
negative symptoms
deficit syndrome

Additional relevant MeSH terms:
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Antipsychotic Agents
Carbidopa, levodopa drug combination
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Aromatic Amino Acid Decarboxylase Inhibitors
Enzyme Inhibitors
Adjuvants, Immunologic
Immunologic Factors
Dopamine Agonists