Ctional Relevance of Dopamine Receptors in Healthy Controls and Patients With Schizophrenia: Characterization Through [11C]NNC-112 and [18F]Fallypride Positron Emission Tomography - Full Text View

Sponsor:	National Institute of Mental Health (NIMH)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00942981

Purpose

Background:

Some illnesses, such as schizophrenia, have effects on brain cells called dopamine receptors, which are required for normal brain function. People with schizophrenia have difficulty thinking and experience hallucinations and delusions. Medications that change brain dopamine receptors can decrease these hallucinations and delusions.
The cause of schizophrenia and its association with brain dopamine receptors is not known but may be clarified by studying dopamine receptors in people who have dopamine disorders (such as schizophrenia) and those who do not. Researchers are interested in studying the dopamine system to gain a better idea of how dopamine disorders develop, which may lead to better medical care for people with schizophrenia.

Objectives:

- To study the amount and distribution of two types of dopamine receptors.

Eligibility:

Individuals between the ages of 18 and 55 who have schizophrenia.
Healthy volunteers between the ages of 18 and 90.

Design:

Participants will undergo a full screening, with physical and psychological history, a neurological examination, and blood and urine samples.
Participants will have a blood flow map of the brain recorded with a positron emission tomography (PET) brain scan. A magnetic resonance imaging (MRI) scan will also be performed to determine brain anatomy.
To study the amount and distribution of dopamine receptors in the brain, participants will receive a small amount of a radioactive chemical in the vein, followed by a PET scan.
The procedure will be performed twice in two separate sessions, once for [18F]fallypride and once for [11C]NNC-112.

Condition
Schizoaffective Disorder Schizophrenia

Study Type:	Observational
Official Title:	Functional Relevance of Dopamine Receptors in Healthy Controls and Patients With Schizophrenia: Characterization Through [11C]NNC-112 and [18F]Fallypride Positron Emission Tomography

Resource links provided by NLM:

MedlinePlus related topics: Schizophrenia

Drug Information available for: Dopamine Fallypride

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:	150
Study Start Date:	July 2009
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES

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, [11C]NNC-112 and [18F]Fallypride, that bind differentially and with a higher binding potential (BP) than previous compounds to the D1 (NNC-112) or D2/3 (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 D1 and D2/3 receptors to increase the risk for schizophrenia.

STUDY POPULATION

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.

DESIGN

Dopamine D1 and D2/3 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 D1 and D2/3 receptor BP data obtained from this protocol.

OUTCOME MEASURES

Brain dopamine D1 and D2/3 receptor regional binding potentials measured by [11C]NNC-112 and [18F]Fallypride PET.

Eligibility

Ages Eligible for Study:	18 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

INCLUSION CRITERIA:
Subjects will be recruited among individuals volunteering for NIH protocol 95-M-0150, NIH protocol 00-M-0085, or NIH protocol 89-M-0160.
Only adult subjects who are able to provide informed consent will be studied.
Patients will be between 18 and 55 years of age. Healthy controls will be matched by age and sex to the patients.
Control subjects must be healthy based on history, laboratory and physical exam obtained through the above mentioned protocols.
Patients with current psychiatric illness (schizophrenia, schizoaffective disorder, or other psychotic disorder)
Current or prior use (or abuse) of substances that interfere with central dopaminergic signaling (e.g. antipsychotics, dopamine receptor agonists, catechol-o-methyltransferase inhibitors, anticholinergics, MAO-B inhibitors)

EXCLUSION CRITERIA:

Subjects will be excluded if they don't fit the study requirements regarding age, ability to provide informed consent, absence of significant general medical, neurological or psychiatric disorders (except the disorder object of study), or intake of substances that interfere with central dopaminergic signaling.
Controls with current or prior use (or abuse) of substances that interfere with central dopaminergic signaling (e.g. antipsychotics, dopamine receptor agonists, catechol-o-methyltransferase inhibitors, anticholinergics, MAO-B inhibitors)
Controls with current psychiatric illness other than schizophrenia, schizoaffective disorder, or other psychotic disorder
Secondary causes of schizophrenia-like syndromes, e.g. amphetamine abuse, brain infarction, tumor, or trauma
Neurological disorders except those of exclusively peripheral location
Significant prior or current substance abuse, severe systemic disease, hypothyroidism not compensated by medication
Laboratory tests with clinically significant abnormalities
History of a significantly abnormal EEG, cranial CT or MRI
Conditions that increase risk for MRI (pacemaker devices, ferromagnetic metal implants, etc.)
Prior participation in other research protocols such that radiation exposure would exceed the annual NIH RSC limits
Prior participation in other research protocols such that radiation exposure would exceed the annual NIH RSC limits

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00942981

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. 2000 Oct;157(10):1552-62.

Tan HY, Callicott JH, Weinberger DR. Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. Cereb Cortex. 2007 Sep;17 Suppl 1:i171-81. Review.

Weinberger DR. Schizophrenia drug says goodbye to dopamine. Nat Med. 2007 Sep;13(9):1018-9. No abstract available.

Study ID Numbers:	090176, 09-M-0176
Study First Received:	July 18, 2009
Last Updated:	September 19, 2009
ClinicalTrials.gov Identifier:	NCT00942981 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

PET Study
(18F) Fallypride
(11C)NNC-112
Schizoaffective Disorder
Schizophrenia

Schizophrenia
Schizoaffective Disorder
Healthy Volunteer
HV

Additional relevant MeSH terms:

Schizophrenia
Pathologic Processes
Disease

Mental Disorders
Psychotic Disorders
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on November 25, 2009