Identifying Correlates of Brain Microglial Activation in Neuropsychiatric Syndromes: a Dimensional Approach

NCT ID: NCT03705715

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-01
• Study Completion Date: 2028-08-31

Brief Summary

The purpose of this research is to determine whether there is more extensive inflammation in the brain of people with clinical evidence of neuropsychiatric syndromes, such as mood disorder, chronic pain syndrome, dementia, traumatic brain injury, or substance abuse. The research will also explore whether there is more inflammation in patients with more neuropsychiatric symptoms. Inflammation in the brain will identified by using Positron Emission Tomography (PET) with the radiotracer [11C]PBR-28 or [11C]ER176.

Detailed Description

This study will explore whether brain microglial activation (which leads to an inflammatory response) is more extensive in individuals with clinical evidence of neuropsychiatric syndromes and whether the extent of microglial activation is proportional to the extent of neuropsychiatric symptoms.

More specifically, the hypothesis is that:

1. Brain microglial activation is more substantial in the presence of neuropsychiatric illness, and the extent of brain microglial activation is proportional to severity of phenotypic presentation of neuropsychiatric illness (i.e. depression, cognitive impairment, fatigue, etc.) in a given patient.

2. Specific brain regions where enhanced microglial activation is present underlie a portion of phenotypic variance in neuropsychiatric patients

3. Combinations of neuropsychiatric phenotypes rather than specific differences in immune mechanisms underlie the contribution of central immune activation to a specific neuropsychiatric diagnosis.

The following measures will be obtained:

1. microglial activation as quantified by PET using the radiotracer [11C]PBR-28 or [11C]ER176. ([11C]PBR-28 and [11C]ER176 specifically bind translocator protein (TSPO), which is associated with microglial activation and can thus serve as an in vivo biomarker of microglial activation and neuroinflammation. TSPO is also called the peripheral benzodiazepine receptor (PBR))

2. dimension of specific neuropsychiatric symptoms (Hamilton Depression Rating Scale (HDRS), Montreal Cognitive Assessment (MoCA), Positive and Negative Affect Schedule (PANAS))

3. presence/absence of a specific neuropsychiatric diagnosis (Dementing Illnesses, Traumatic Brain Injury, Major Depression, Bipolar Disorder, Pain Syndromes, Other Affective Disorders, etc.)

Using the above measures, correlations (and brain regional correlations) between the extent of microglial activation and the presence of a dimension of neuropsychiatric symptoms will be tested for. Following this, the presence of microglial activation (and brain regional microglial activation) 1) between healthy control volunteers and volunteers with neuropsychiatric syndromes and 2) between the various neuropsychiatric syndromes/diagnoses will be tested for.

Conditions

Neuropsychiatric Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

PET with radiotracer [11C]PBR-28 or [11C]ER176

PET with radiotracer \[11C\]PBR-28 or \[11C\]ER176 will be performed. \[11C\]PBR-28 or \[11C\]ER176 will be injected into subjects' veins during PET scanning.

Group Type: EXPERIMENTAL

PET with radiotracer [11C]PBR-28 ( or [11C]ER176)

Intervention Type: DRUG

\[11C\]PBR-28 or \[11C\]ER176 will be injected into subjects' veins during PET scanning.

PET with radiotracer [11C]PBR-28 or [11C]ER176 and affective challenge

PET with radiotracer \[11C\]PBR-28 or \[11C\]ER176 will be performed. \[11C\]PBR-28 or \[11C\]ER176 will be injected into subjects' veins during PET scanning. Affective challenge (e.g. induction of mood, affective pain) will be presented to the patient during the PET scanning period.

Group Type: EXPERIMENTAL

No interventions assigned to this group

Interventions

PET with radiotracer [11C]PBR-28 ( or [11C]ER176)

\[11C\]PBR-28 or \[11C\]ER176 will be injected into subjects' veins during PET scanning.

Intervention Type: DRUG

Affective challenge

Affective challenge is the induction of, for example, mood or affective pain.

Intervention Type: OTHER

Other Intervention Names

[O-methyl-11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy- 5-pyridinamine; biobehavioral challenges

Eligibility Criteria

Inclusion Criteria

• Must be between 18-80 years old
• Males or females
• Must be right handed
• Must be able to sit unaccompanied for long periods of time with little body movement
• Must be illicit drug free at time of scanning as appropriate (UDS negative),
• Must be either healthy (without medical, neurological, psychiatric illness) or have a diagnosis of a neuropsychiatric syndrome (mood disorder, chronic pain syndrome, dementias, traumatic brain injury, substance/alcohol use disorder).
• Healthy Control volunteers must be medication free (≥ 14 days)
• Illicit drug free at time of scanning (verified by negative urine drug screen)

Exclusion Criteria

• Must not be a smoker.
• Females must not be pregnant or nursing.
• Must not suffer from claustrophobia
• Must not be PBR-28 low affinity binder (or using the [11C]ER176 study radiotracer)
• Healthy control volunteers must not have on-going, chronic, or relapsing/remitting medical, psychiatric (absence of both DSM-IV Axis I and/or Axis II disorders), or neurological illness as determined by combination of history, medical record, and/or examination.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Alan Prossin

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alan Prossin, MBBS

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

BBSB at UTHealth

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Alan Prossin, MBBS

Role: CONTACT

alan.prossin@uth.tmc.edu

713-486-2836

Facility Contacts

alan R Prossin, MBBS

Role: primary

alan.prossin@uth.tmc.edu

713-486-2836

Other Identifiers

HSC-MS-15-0744

Identifier Type: -

Identifier Source: org_study_id