Schizophrenia
Conditions
Brief summary
The purpose of this research is to use specialized brain imaging techniques, Positron Emission Tomography (PET) scan and Magnetic Resonance Imaging (MRI), to learn more about the brain chemistry, e.g., how neurotransmitters and receptors in the brain function in people with schizophrenia compared to healthy controls.
Detailed description
Abnormalities in brain chemistry can be responsible for the hallucinations and delusions; thus, by treating these abnormalities, physicians can reduce symptoms of schizophrenia. In this study, investigators aim to examine the characteristics of two investigational radiotracers, \[18F\]AZAN and \[18F\]ASEM, in the brains of people with schizophrenia and healthy controls. Radiotracers are drugs in which one or more atoms are labeled with a small amount of radioactivity that allows investigators to see how the drug works in humans using PET and MRI brain imaging techniques.
Interventions
DRUG[18F]ASEM
\[18F\]ASEM demonstrated excellent imaging properties, as was recently confirmed by others. \[18F\]ASEM is the 1st validated α7 human PET radiotracer to examine α7-nAChR characteristics in the living brain of SCZ patients. Previous α7 studies in the SCZ literature were done using brains harvested post-mortem, and under variable storage conditions. The proposed studies will also determine α4β2-nAChR \[18F\]AZAN binding characteristics in the same subjects who complete α7-nAChR PET studies with \[18F\]ASEM, which will be highly significant for understanding these receptors in SCZ.
DRUG[18F]AZAN
The most widely used PET radioligand for human imaging of α4β2-nAChR is 2-\[18F\]FA. Because 2-\[18F\]FA exhibits very slow brain kinetics, the investigators developed \[18F\]AZAN, a highly α4β2 specific tracer with optimal brain kinetics. Therefore, the proposed studies will utilize \[18F\]AZAN to determine α4β2-nAChR \[18F\]AZAN binding characteristics in the same subjects who complete α7-nAChR PET studies with \[18F\]ASEM, which will be highly significant for understanding these receptors in SCZ.
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion Criteria for Healthy Subjects * Between 18-55 years old (inclusive)men and women. * Black/African-American or non Hispanic White/Caucasian * Healthy as determined by medical history, physical examination, clinical laboratory test results, vital signs, and ECG within the reference ranges for the population or results within acceptable deviations that are not clinically significant as determined by study physician. * Have sufficient arterial or venous access, as determined by Interventional neuroradiologist or anesthesiologist. * Able to sign written informed consent and to comply with the study restrictions. * No DSM-5diagnosis on axes I, II, III, and no currently active psychiatric diagnoses or substance use disorders as determined by \[SCID\] * If Tobacco or Nicotine user-willing to abstain from products at least 3 hours prior to all PET scans until completion of the scan. Inclusion Criteria for Patients with Schizophrenia * Subjects with known chronic SCZ or acute psychotic episodes where suspicion of SCZ is high * Patients who are drug naïve or nonadherent based on patient report or collateral information OR: a. Subjects on stable (3-months) doses of antipsychotics including risperidone, aripiprazole, ( Part 1 ) Note: if the results of Part 2 ( Aim 4 ) support the null hypothesis for olanzapine effects then investigators will include subjects with schizophrenia on chronic olanzapine. b. Subjects off and then on olanzapine only ( Part 2 ) * 3.18-55 years old (inclusive). * 4.Male and female subjects meeting DSM-5 diagnostic criteria for a schizophrenia spectrum disorder, verified by SCID-1/P and schizophreniform (\<1 year of symptoms5.Black/African-American or non-hispanic White/Caucasian
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relationship between α4β2/α7-nAChR receptor binding VT and cognitive functioning, as measured by the Calibrated Neuropsychological Normative Scale (CNNS) score in SCZ vs. matched controls. | 60-74 days | The Primary Outcome Measure is the comparison of the interaction between α4β2/α7-nAChR volume of distribution (VT, represented as ml of plasma/cm\^3 of tissue) and the Calibrated Neuropsychological Normative Scale (CNNS) score in SCZ vs. matched controls. |
| Relationship between α4β2-nAChR receptor binding VT and performance on the Spatial Attention Resource Allocation Task (SARAT) in SCZ vs. matched controls. | 60-74 days | The Primary Outcome Measure is comparison of the main effect of volume of distribution (VT, represented as ml of plasma/cm\^3 of tissue) on the Spatial Attention Resource Allocation Task (SARAT) score in SCZ vs. matched controls. |
| Relationship between α4β2/α7-nAChR receptor binding VT and cognitive functioning, as measured by the Spatial Attention Resource Allocation Task (SARAT) in SCZ vs. matched controls. | 60-74 days | The Primary Outcome Measure is the comparison of the interaction between α4β2/α7-nAChR volume of distribution (VT, represented as ml of plasma/cm\^3 of tissue) and the Spatial Attention Resource Allocation Task (SARAT) score in SCZ vs. matched controls. |
| Receptor binding of [18F] ASEM-PET to nicotinic brain receptors (α7-nAChRs) in adults ages 18-55 year with SCZ vs. matched controls. | 60-74 days | The Primary Outcome Measure is volume of distribution (VT, represented as ml of plasma/cm\^3 of tissue) of alpha-7 nicotinic receptors (α7-nAChR) bound to by the \[18F\]ASEM radio tracer in the brain, comparing VT in people with SCZ with VT in otherwise healthy adults matched for all demographics (smoking status, age, sex, race/genotype, parental education). |
| Receptor binding of [18F]AZAN to α4β2 nicotinic acetylcholine receptors (α4β2-nAChR) in adults ages 18-55 years with SCZ vs. matched controls. | 60-74 days | The Primary Outcome Measure is volume of distribution (VT, represented as ml of plasma/cm\^3 of tissue) of α4β2 nicotinic acetylcholine receptors (α4β2-nAChR) bound to by the \[18F\]AZAN radio tracer in the brain, comparing % receptor occupancy in people with SCZ with VT in otherwise healthy adults matched for all demographics (smoking status, age, sex, race/genotype, parental education). |
| Relationship between α7-nAChR receptor binding VT and negative symptoms in adult patients ages 18-55 yrs with SCZ. | 60-74 days | The Primary Outcome Measure is the main effect of α7-nAChR receptor volume of distribution (VT, represented as ml of plasma/cm\^3 of tissue) on negative symptoms as measured by the negative symptom sub-scale of the Positive and Negative Symptoms Scale (PANSS) in SCZ patients. |
| Relationship between α4β2-nAChR receptor binding VT and negative symptoms in adult patients ages 18-55 yrs with schizophrenia (SCZ). | 60-74 days | The Primary Outcome Measure is the main effect of α4β2-nAChR volume of distribution (VT, represented as ml of plasma/cm\^3 of tissue) and the negative symptom sub-scale score of the Positive and Negative Symptoms Scale (PANSS) in SCZ. |
| Relationship between α7-nAChR receptor binding VT and cognitive symptoms, as measured by the Stroop Color-Word Interference Test in SCZ vs. matched controls. | 60-74 days | The Primary Outcome Measure is the comparison of the main effect of receptor volume of distribution (VT, represented as ml of plasma/cm\^3 of tissue) on the Stroop Color-Word Interference Task score in SCZ vs. matched controls. |
| Relationship between α4β2-nAChR receptor binding VT and cognitive symptoms, as measured by the Stroop Color-Word Interference Task in SCZ vs. matched controls. | 60-74 days | The Primary Outcome Measure is comparison of the main effect of volume of distribution (VT, represented as ml of plasma/cm\^3 of tissue) on the Stroop Color-Word Interference Test score between SCZ patients and matched controls. |
| Relationship between α7-nAChR receptor binding VT and performance on the Spatial Attention Resource Allocation Task (SARAT) in SCZ vs. matched controls. | 60-74 days | The Primary Outcome Measure is comparison of the main effect of volume of distribution (VT, represented as ml of plasma/cm\^3 of tissue) on the Spatial Attention Resource Allocation Task (SARAT) in SCZ vs. matched controls. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relationship between the single nucleotide polymorphism (SNP) CHRNA7 rs3087454 and race in SCZ vs. matched controls. | 60-74 days | The Primary Outcome Measure is the correlation between CHRNA7 rs3087454 and and race (non-Hispanic Caucasians and African Americans) in SCZ vs. matched controls. |
| Relationship between α4β2/α7-nAChR VT and tobacco use disorder in SCZ patients who are smokers vs. non-smoker SCZ patients treated with olanzapine. | 60-74 days | The Primary Outcome Measure is the relationship between α4β2/α7-nAChR (VT, represented as ml of plasma/cm\^3 of tissue) and smoking status in SCZ taking olanzapine who smoke tobacco. |
Countries
United States
Outcome results
None listed