SchizophreniaPhase 2NCT01636037
Antipsychotic Augmentation With L-Dopa
A Phase 2 study testing levodopa/carbidopa (generic version of Sinemet) in people with Schizophrenia, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- levodopa/carbidopa (generic version of Sinemet)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2012to Jan 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- SCID-confirmed (Structured Clinical Interview for DSM-IV Axis I Disorders) diagnosis of schizophrenia
- ages 18-55
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
- L-dopa will prove effective in improving deficit (also called 'primary negative' e.g. amotivation) and cognitive symptoms in schizophrenia.
- It will be well tolerated and not increase risk of psychotic symptoms when administered in conjunction with their regular antipsychotic medications.
Read the 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.
- Conditions
- Schizophrenia
- Being tested
- levodopa/carbidopa (generic version of Sinemet)
- Keywords
- schizophrenia, negative symptoms, deficit syndrome, SANS, Sinemet, L-dopa, levodopa, carbidopa, augmentation, antipsychotics
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
levodopa/carbidopa (generic version of Sinemet)Drug
Also called Levodopa/carbidopa, Sinemet
Oral levodopa 900mg daily as tolerated.
| Study group | Role | What they receive |
|---|---|---|
| L-Dopa (Sinemet) | Experimental | Augmentation of current antipsychotic treatment with oral L-Dopa (levodopa/carbidopa) up to 900mg daily for 8 weeks Receives: Drug: levodopa/carbidopa (generic version of Sinemet) |
What is being measured
The primary outcome is the main question the study is designed to answer.
SANS - Schedule for the Assessment of Negative Symptoms
Measured: 8 weeks
Secondary outcomes (17)
MATRICS-Consensus Cognitive Battery
Measured: 8 weeks
BPRS - Brief Psychotic Rating Scale
Measured: 8 weeks
SAPS - Schedule for the Assessment of Positive Symptoms
Measured: 8 weeks
NIMH-MATRICS Brief Negative Symptoms Scale
Measured: 8 weeks
CGI-S - Clinical Global Impression - Severity Scale
Measured: 8 weeks
QLS - Quality of Life Scale
Measured: 8 weeks
CDS - Calgary Depression Scale
Measured: 8 weeks
SAS - Simpson Angus Scale for Extrapyramidal Symptoms
Measured: 8 weeks
BARS - Barnes Akathisia Rating Scales
Measured: 8 weeks
AIMS - Abnormal Involuntary Movement Scale
Measured: 8 weeks
UKU - Udvalg for Kliniske Undersogelses
Measures General Side Effects
Measured: 8 weeks
LUNSERS - Liverpool University Neuroleptic Side-Effect Rating Scale
Measured: 8 weeks
BIS-11 - Barrett Impulsivity Scale
Measured: 8 weeks
Y-BOCS - Yale-Brown Obsessive Compulsive Scale
Measured: 8 weeks
DAI - Drug Attitude Inventory
Measured: 8 weeks
fMRI - Functional Magnetic Resonance Imaging
Changes in Regional Brain Activity
Measured: 8 weeks
SWN - Subjective Well-Being on Neuroleptics Scale
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2012 (estimated)
- Study startSep 2012
- Primary completionDec 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, George Foussias, Centre for Addiction and Mental Health
- Investigators
- Gary Remington, MD PhD FRCPC, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01636037
- Sponsor's protocol ID
- 156/2011
- Status last verified
- Mar 2016
- First submitted
- 5 Jul 2012
- Last updated
- 15 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Augmentation of Antipsychotics With L-Dopa (Sinemet)
- ClinicalTrials.gov ID
- NCT01636037
- Acronym / sponsor ID
- 156/2011
- Conditions
- Schizophrenia
- Keywords
- schizophrenia, negative symptoms, deficit syndrome, SANS, Sinemet, L-dopa, levodopa, carbidopa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Dec 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 10 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- L-dopa will prove effective in improving deficit (also called 'primary negative' e.g. amotivation) and cognitive symptoms in schizophrenia.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| L-Dopa (Sinemet) | Experimental | Drug: levodopa/carbidopa (generic version of Sinemet)Augmentation of current antipsychotic treatment with oral L-Dopa (levodopa/carbidopa) up to 900mg daily for 8 weeks |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- SCID-confirmed (Structured Clinical Interview for DSM-IV Axis I Disorders) diagnosis of schizophrenia
- ages 18-55
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| levodopa/carbidopa (generic version of Sinemet)Also: Levodopa/carbidopa, SinemetOral levodopa 900mg daily as tolerated. | Drug | L-Dopa (Sinemet) |
Primary outcome
SANS - Schedule for the Assessment of Negative Symptoms
Time frame: 8 weeks
17 secondary outcomes
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
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
SWN - Subjective Well-Being on Neuroleptics Scale
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2016.
- Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital. It is fully affiliated with the University of Toronto, and is a PAHO/WHO Collaborating Centre.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary Remington, MD PhD FRCPC principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing levodopa/carbidopa (generic version of Sinemet) in people with Schizophrenia, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SANS - Schedule for the Assessment of Negative Symptoms (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2016.