Augmentation of antipsychotics with levodopa - fMRI study to examine neurobiological effects of L-dopa in Schizophrenia
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- SANS - Schedule for the Assessment of Negative Symptoms
Study Overview
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.
a. L-dopa will prove effective in improving deficit (also called ’primary negative’ e.g. amotivation) and cognitive symptoms in schizophrenia.
b. It will be well tolerated and not increase risk of psychotic symptoms when administered in conjunction with their regular antipsychotic medications.
Study Design
- Study Type
- Interventional
- Allocation
- Not Applicable
- Masking
- Not Applicable
Eligibility Criteria
- Ages
- 18.00 Year(s) to 55.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •(i) SCID-confirmed (Structured Clinical Interview for DSM-IV Axis I Disorders) diagnosis of schizophrenia (ii) ages 18-55 (iii) treatment with antipsychotic monotherapy; antipsychotic dose within, but not below or exceeding, current recommended guidelines.
Exclusion Criteria
- •(i) history of substance abuse or dependence within 3 months (ii)positive urine drug screen; (iii) history or evidence of any disorder that might adversely influence cognitive measures (e.g. mental retardation); (iv) presence of serious neurological or general medical condition (e.g., Parkinson’s disease, cardiac arrhythmia, epilepsy); (v) clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematologic, hepatic, pulmonary (including bronchial asthma), or renal disease, narrow-angle glaucoma, malignant melanoma; (vi) pregnancy/nursing (vii) nonselective monoamine oxidase (MAO) inhibitors within 2 weeks or use of a sympathomimetic amine; (viii) evidence of acute psychotic exacerbation in the last month; (x) acute suicidal risk; (xi) change in dose of current antipsychotic or concomitant psychotropic medications in the 8 weeks prior to study entry; (xii)presence of depressive symptoms, as defined by score >2 on 50% of items (‘moderate’), using the Calgary Depression Scale (xiii) parkinsonian symptoms, as defined by a score >8 on the Simpson-Angus Scale for Extrapyramidal Symptoms.
Outcomes
Primary Outcomes
SANS - Schedule for the Assessment of Negative Symptoms
Time Frame: 8 weeks
Secondary Outcomes
- MATRICS-Consensus Cognitive Battery(8weeks)
- BPRS-Brief Psychotic Rating Scale(8weeks)
- SAPS-Schedule for the Assessment of Positive Symptoms(8weeks)
- NIMH-MATRICS Brief Negative Symptoms Scale(8weeks)
- CGI-S - Clinical Global Impression - Severity Scale(8weeks)
- SAS - Simpson Angus Scale for Extrapyramidal Symptoms(8weeks)
- BARS - Barnes Akathisia Rating Scales(8weeks)
- AIMS - Abnormal Involuntary Movement Scale(8weeks)
- QLS - Quality of Life Scale(8weeks)
- CDS - Calgary Depression Scale(8weeks)
- UKU - Udvalg for Kliniske Undersogelses(8weeks)
- BIS-11 - Barrett Impulsivity Scale(8weeks)
- Y-BOCS - Yale-Brown Obsessive Compulsive Scale(8weeks)
- DAI - Drug Attitude Inventory(8weeks)
- fMRI - Functional Magnetic Resonance Imaging(Changes in Regional Brain Activity)
- SWN - Subjective Well-Being on Neuroleptics Scale(8weeks)
- LUNSERS - Liverpool University Neuroleptic Side-Effect Rating Scale(8weeks)