Functional Relevance of Dopamine Receptors in Healthy Controls and Patients With Schizophrenia: Characterization Through [11C]NNC-112 and [18F]Fallypride Positron Emission Tomography
|First Received Date ICMJE||July 18, 2009|
|Last Updated Date||January 24, 2017|
|Start Date ICMJE||July 15, 2009|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Regional binding potentials of [11C]NNC-112 and [18F]Fallypride|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00942981 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Functional Relevance of Dopamine Receptors in Healthy Controls and Patients With Schizophrenia: Characterization Through [11C]NNC-112 and [18F]Fallypride Positron Emission Tomography|
|Official Title ICMJE||Functional Relevance of Dopamine Receptors in Healthy Controls and Patients With Schizophrenia: Characterization Through [11C]NNC-112 and [18F]Fallypride Positron Emission Tomography|
- To study the amount and distribution of two types of dopamine receptors.
Dopaminergic (DA) modulation of brain function is disturbed in several disabling psychiatric disorders and represents the target of key psychopharmacologic agents, such as neuroleptics. Schizophrenia has been considered a prototype of dysregulated DA signaling, with associated prefrontal cortex (PFC) dysfunction. Prevailing views attribute key symptoms of schizophrenia to deficient DA signaling within mesocortical DA tracts. Little is known, however, about the pre-, intra-, and post-synaptic processes that contribute to dopaminergic dysregulation. Regional cortical DA activity, critical to these processes, has been difficult to measure in patients with the available imaging techniques. The current clinical study aims to address this open issue by taking advantage of two recently developed positron emission tomography (PET) radioligands, [(11)C]NNC-112 and [(18)F]Fallypride, that bind differentially and with a higher binding potential (BP) than previous compounds to the D(1) (NNC-112) or D(2/3) (fallypride) receptors. By measuring the regional BP of these two compounds, cortical and subcortical DA receptor anomalies will be characterized in schizophrenia. Within the Clinical Brain Disorders Branch (CBDB), this PET protocol is expected to add crucial information about DA receptor status to ongoing regional cerebral blood flow (rCBF), magnetic resonance imaging (MRI), magneto-encephalography (MEG) and genetic studies. It will lead to an improved understanding of the modulatory influence of DA on frontal lobe functioning and facilitate the study of how genetic polymorphisms interact with regional changes in D(1) and D(2/3) receptors to increase the risk for schizophrenia.
Some specific hypotheses to be tested are as follows:
D1 BP in frontal cortex will be affected by age, elevated in schizophrenia and inversely correlated with cognitive performance in patients and healthy controls.
Cortical D2/3 receptor BP will be affected by age and inversely correlated with performance on tests of frontal lobe function in patients and healthy controls.
Striatal D2/3 receptor BP will be altered in patients.
Polymorphisms in the catechol-O-methyl transferase (COMT), D1 and D2 genes as well as other schizophrenia risk genes will affect DA receptor BP in frontal cortex.
The ratio of cortical D1 and D2/3 receptor BPs will be affected by age and related to risk for schizophrenia, cognitive performance and polymorphisms in the COMT gene and other schizophrenia risk genes
It will include 50 patients with schizophrenia, schizoaffective disorder or other psychotic disorders aged 18-55, and 150 healthy controls, aged 18-90. Fifty of the controls will be matched to the patients by age and sex.
Dopamine D(1) and D(2/3) receptor regional binding potentials (BP) will be quantified by PET in medication-free patients and controls. High resolution T1-weighted magnetic resonance imaging (MRI) scans will be obtained for co-registration purposes. Additionally, through enrollment in other ongoing protocols (00-M-0085, 90-M-0014, 01-M-0232, 95-M-0150, 89-M-0160), rCBF, functional MRI, cognitive and genetic data will be obtained and compared with D(1) and D(2/3) receptor BP data obtained from this protocol.
Brain dopamine D(1) and D(2/3) receptor regional binding potentials measured by [[(11)C]NNC-112 and [(18)F]Fallypride PET.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Time Perspective: Other|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||330|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
EXCLUSION CRITERIA: (for patients and controls except where indicated)
|Ages||18 Years to 90 Years (Adult, Senior)|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00942981|
|Other Study ID Numbers ICMJE||090176, 09-M-0176|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Mental Health (NIMH)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||October 31, 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP