Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Antipsychotic Augmentation With L-Dopa

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Centre for Addiction and Mental Health
Sponsor:
Information provided by (Responsible Party):
George Foussias, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT01636037
First received: July 5, 2012
Last updated: September 5, 2014
Last verified: September 2014

July 5, 2012
September 5, 2014
September 2012
September 2015   (final data collection date for primary outcome measure)
SANS - Schedule for the Assessment of Negative Symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01636037 on ClinicalTrials.gov Archive Site
  • MATRICS-Consensus Cognitive Battery [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • BPRS - Brief Psychotic Rating Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • SAPS - Schedule for the Assessment of Positive Symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • NIMH-MATRICS Brief Negative Symptoms Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • CGI-S - Clinical Global Impression - Severity Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • QLS - Quality of Life Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • CDS - Calgary Depression Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • SAS - Simpson Angus Scale for Extrapyramidal Symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • BARS - Barnes Akathisia Rating Scales [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • AIMS - Abnormal Involuntary Movement Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • UKU - Udvalg for Kliniske Undersogelses [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measures General Side Effects
  • LUNSERS - Liverpool University Neuroleptic Side-Effect Rating Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • BIS-11 - Barrett Impulsivity Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Y-BOCS - Yale-Brown Obsessive Compulsive Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • DAI - Drug Attitude Inventory [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • fMRI - Functional Magnetic Resonance Imaging [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Changes in Regional Brain Activity
  • SWN - Subjective Well-Being on Neuroleptics Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • MATRICS-Consensus Cognitive Battery [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • BPRS - Brief Psychotic Rating Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • SAPS - Schedule for the Assessment of Positive Symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • NIMH-MATRICS Brief Negative Symptoms Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • CGI-S - Clinical Global Impression - Severity Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • QLS - Quality of Life Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • CDS - Calgary Depression Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • SAS - Simpson Angus Scale for Extrapyramidal Symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • BARS - Barner Akathisia Rating Scales [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • AIMS - Abnormal Involuntary Movement Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • UKU - Udvalg for Kliniske Undersogelses [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measures General Side Effects
  • LUNSERS - Liverpool University Neuroleptic Side-Effect Rating Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • BIS-11 - Barrett Impulsivity Sclae [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Y-BOCS - Yale-Brown Obsessive Compulsive Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • DAI - Drug Attitude Inventory [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • fMRI - Functional Magnetic Resonance Imaging [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Changes in Regional Brain Activity
  • SWN - Subjective Well-Being on Neuroleptics Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Antipsychotic Augmentation With L-Dopa
Augmentation of Antipsychotics With L-Dopa (Sinemet)

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Schizophrenia
Drug: levodopa/carbidopa (generic version of Sinemet)
Oral levodopa 300mg daily as tolerated.
Other Names:
  • Levodopa/carbidopa
  • Sinemet
Experimental: L-Dopa (Sinemet)
Augmentation of current antipsychotic treatment with oral L-Dopa (levodopa/carbidopa) 300mg daily for 8 weeks
Intervention: Drug: levodopa/carbidopa (generic version of Sinemet)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
24
September 2015
September 2015   (final data collection date for primary outcome measure)

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)
Both
18 Years to 55 Years
No
Contact: George Foussias, MD PhD FRCPC 416-535-8501 ext 34390 george_foussias@camh.net
Contact: Carol Borlido, BSc 416-535-8501 ext 34321 carol_borlido@camh.net
Canada
 
NCT01636037
156/2011
Yes
George Foussias, Centre for Addiction and Mental Health
Centre for Addiction and Mental Health
Not Provided
Principal Investigator: Gary Remington, MD PhD FRCPC Centre for Addiction and Mental Health
Centre for Addiction and Mental Health
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP