Antipsychotic Augmentation With L-Dopa

Schizophrenia Clinical Trial

Official title:

Augmentation of Antipsychotics With L-Dopa (Sinemet)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01636037
• Other study ID #: 156/2011
• Status: Completed
• Phase: Phase 2
• First received: July 5, 2012
• Last updated: March 11, 2016
• Start date: September 2012
• Est. completion date: January 2016

Study information

• Verified date: March 2016
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: January 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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)

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

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

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SANS - Schedule for the Assessment of Negative Symptoms		8 weeks	No
Secondary	MATRICS-Consensus Cognitive Battery		8 weeks	No
Secondary	BPRS - Brief Psychotic Rating Scale		8 weeks	No
Secondary	SAPS - Schedule for the Assessment of Positive Symptoms		8 weeks	No
Secondary	NIMH-MATRICS Brief Negative Symptoms Scale		8 weeks	No
Secondary	CGI-S - Clinical Global Impression - Severity Scale		8 weeks	No
Secondary	QLS - Quality of Life Scale		8 weeks	No
Secondary	CDS - Calgary Depression Scale		8 weeks	No
Secondary	SAS - Simpson Angus Scale for Extrapyramidal Symptoms		8 weeks	No
Secondary	BARS - Barnes Akathisia Rating Scales		8 weeks	No
Secondary	AIMS - Abnormal Involuntary Movement Scale		8 weeks	No
Secondary	UKU - Udvalg for Kliniske Undersogelses	Measures General Side Effects	8 weeks	No
Secondary	LUNSERS - Liverpool University Neuroleptic Side-Effect Rating Scale		8 weeks	No
Secondary	BIS-11 - Barrett Impulsivity Scale		8 weeks	No
Secondary	Y-BOCS - Yale-Brown Obsessive Compulsive Scale		8 weeks	No
Secondary	DAI - Drug Attitude Inventory		8 weeks	No
Secondary	fMRI - Functional Magnetic Resonance Imaging	Changes in Regional Brain Activity	8 weeks	No
Secondary	SWN - Subjective Well-Being on Neuroleptics Scale		8 weeks	No

External Links

•   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.