Positron Emission Tomography (PET) Imaging of Glial Activation in Psychotic Disease States

PET Imaging of Glial Activation in Psychotic Disease States

Many neurological diseases, including AIDS dementia, Alzheimer's disease and schizophrenia, involve an inflammatory component thought to specifically involve glial cell activation. The Investigators has been concerned with the development of tools for noninvasive imaging of inflammatory processes in psychotic disease. Here, the investigators aim to use PET-based neuroimaging with carbon-11 N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide, ([11C]DPA)-713 to quantify regional distribution of translocator protein (TSPO), a putative marker of inflammation, in the brains of patients with schizophrenia and bipolar disorder, type I. The investigators will focus on patients in the early stages of disease (within first five years of onset of schizophrenia diagnosis and within first five years of first manis, respectively) to minimize the confounds of age-, chronic illness-, and medication- effects on our results.

Study Overview

• Status: Terminated
• Conditions: Schizophrenia; Bipolar Disorder
• Intervention / Treatment: Drug: [11C]DPA-713

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy volunteers 18-65 years of age
• Patients diagnosed with recent onset schizophrenia (within 5 years of onset), 18-65 years of age
• Patients diagnosed with recent onset bipolar disorder (within 5 years of onset of first mania), 18-65 years of age
• screening laboratory tests will be obtained for subjects within a 10 day period prior to the PET study and the results must be within normal limits for gender and age. These tests will be repeated with a 7-day window following the PET study
• EKG conducted within 10 day period prior to the PET study. The EKG will be repeated within 7 days following the study.
• Subject agrees to return to the Hospital for a follow-up EKG and laboratory testing of blood and urine.
• For females of childbearing potential, negative serum pregnancy test within a 10 day period prior to PET study.

Exclusion Criteria:

• history of recent nosocomial infection,
• history of chronic neurological disorder, such as multiple sclerosis or epilepsy, or structural,central nervous system (CNS) abnormality such as stroke or arteriovenous malformation,
• history of head injury with loss of consciousness > 1 hour,
• history of active substance abuse as defined by substance abuse including alcohol abuse over the 6 months prior to the study,
• dependence on benzodiazepine medication
• contraindications to MRI scanning to include pacemakers, metallic implants/prosthesis or prohibitive claustrophobia, etc.
• contraindications to PET scanning to include pregnancy, etc. For females of childbearing potential, negative serum pregnancy test less than 10 days prior to PET study
• ECG demonstrating the patient is not in a sinus rhythm or is having acute ischemia.
• any medical condition that in the opinion of the study investigators would constitute a safety risk to the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Schizophrenia Disorder; Patients with Schizophrenia Disorder will be imaged with [11C] DPA-713	Drug: [11C]DPA-713; [11C]DPA-713 PET imaging
Experimental: Patients with Bipolar Disorder; Patients with Bipolar Disorder will be imaged with [11C] DPA-713	Drug: [11C]DPA-713; [11C]DPA-713 PET imaging
Experimental: Control; Normal volunteers will be imaged with [11C] DPA-713	Drug: [11C]DPA-713; [11C]DPA-713 PET imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and Specificity of ([11C]DPA)-713 PET brain imaging in patients with recent onset schizophrenia and in patients with recent onset of mania	To determine regional brain uptake of this radioligand in patients with recent onset schizophrenia and in patients with recent onset of mania	within five years of onset of schizophrenia or within five years of first manic episode

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET Imaging of microglial activation	To evaluate changes in activation of microglia in patients with acute schizophrenia and bipolar disorder relative to controls	5 years

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Martin Pomper, MD,PhD, Professor

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: August 15, 2017
• First Submitted That Met QC Criteria: August 18, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): September 10, 2020
• Last Update Submitted That Met QC Criteria: September 8, 2020
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Bipolar and Related Disorders; Schizophrenia; Bipolar Disorder
• Other Study ID Numbers: NA_00037683