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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00942981
First received: July 18, 2009
Last updated: March 14, 2014
Last verified: January 2014
  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 60 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:


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

Primary Outcome Measures:
  • Regional binding potentials of [11C]NNC-112 and [18F]Fallypride

Estimated Enrollment: 200
Study Start Date: July 2009
  Hide Detailed Description

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, [(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

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 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.

OUTCOME MEASURES

Brain dopamine D(1) and D(2/3) receptor regional binding potentials measured by [[(11)C]NNC-112 and [(18)F]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 A Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and Their Siblings (PI: Daniel Weinberger, M.D.), NIH protocol 00-M-0085 Structural and Functional Imaging of Neuropsychiatric Patients and Normal Volunteers with 3.0 Tesla MRI and Magnetoencephalography. (P.I.: Venkata Mattay, MD) or NIH protocol 89-M-0160 Inpatient Evaluation of Neuropsychiatric Patients (PI: Jose Apud, M.D. Ph.D).
  • Only adult subjects who are able to provide informed consent will be studied.
  • Patients will be between 18 and 60 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 and will be included up to the age of 90 years.

EXCLUSION CRITERIA: (for patients and controls except where indicated)

  • 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.
  • Current psychiatric illness except for patients with schizophrenia, schizoaffective disorder or other psychotic disorder
  • 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) except for patients on antipsychotics and other psychotropic agents which will be discontinued for at least 4 weeks under protocol 89-M-0160.
  • 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
  • Any medical condition that, in the opinion of the investigators, would interfere with the safe conduct of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Jasmin Czarapata, Ph.D. (301) 435-7645 js733c@nih.gov
Contact: Karen F Berman, M.D. (301) 496-7603 bermank@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Karen F Berman, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00942981     History of Changes
Other Study ID Numbers: 090176, 09-M-0176
Study First Received: July 18, 2009
Last Updated: March 14, 2014
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
Healthy Volunteer
HV

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on October 23, 2014