Selective PET Imaging of Astrocytes and Microglia in Alzheimer's Disease

March 31, 2026 updated by: The Methodist Hospital Research Institute
Inflammation occurs in many brain diseases including Alzheimer's disease. In Alzheimer's disease, an abnormal protein called amyloid starts accumulating decades before the start of forgetfulness. However, scientists have reported that inflammation but not amyloid is linked to forgetfulness and the topography of brain inflammation and tau buildup are closely correlated in patients with mild cognitive impairment due to Alzheimer's disease. New medications are under development to help healing and prevent permanent damage in the brain. To see if inflammation is improving or getting worse with these medications, investigators can watch inside of the brain using a special camera called positron emission tomography (PET). It is currently possible to watch inflammation in the brain by taking pictures of a molecule called translocator protein (TSPO). But the problem is that by imaging TSPO, investigators can catch changes in more than one kind of cells. The information is not specific to each cell type. Such vague information is not completely useful to monitor the effect of new medications for inflammation. This proposal attempts to develop a novel method to capture changes in each of two major players in inflammation, microglia and astrocytes. To do so, investigators will take selective pictures of one cell type by using a novel imaging agent for PET. Investigators will also take PET pictures of TSPO. Investigators will process these two kinds of PET pictures using advanced mathematical methods and extract specific information on microglia and astrocytes. Our novel method will be useful to monitor new therapies to treat inflammation in the brain.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Inflammation in brain plays critical roles in disease progress and symptom development in a number of brain disorders such as Alzheimer's disease (AD), traumatic brain injury, major depressive disorder, epilepsy, and schizophrenia. Neuroinflammation has been imaged using positron emission tomography (PET) by using translocator protein (TSPO) as the marker. Although TSPO PET studies have provided insight to understand the pathology, some results are difficult to interpret. TSPO imaging has a major limitation of not being selective to one type of glia; it is expressed by both microglia and astrocyte. The current study attempts to overcome this limitation. Monoamine oxidase type-B (MAO-B) is highly expressed by astrocyte and serotonin (5-HT)-releasing neurons but not by microglia. PET studies using a prototype tracer 11C-L-deprenyl detects astrogliosis in mild cognitive impairment (MCI) but this tracer has low levels of specific binding. Preliminary results show that a novel tracer 18F-SMBT-1 developed by Dr. Okamura and his colleagues has several times greater levels of specific binding. The Aims of the current study are to 1) estimate radiation-absorbed doses in 8 healthy people, 2) measure ratios of specific-to-nondisplaceable binding by performing brain scans with and without binding blockade in 5 patients with Alzheimer's disease, 3) measure reproducibility of measuring 18F-SMBT-1 in 8 healthy people, 4) compare MAO-B levels between healthy controls (n = 25) and patients with AD (n = 25), and 5) from 11C-ER176 for TSPO and 18F-SMBT-1, extract cell type specific information for microglia and astrocytes and investigate changes in each cell type In AD.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
71

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Healthy volunteers and patients with Alzheimer's disease

Description

Patients with Alzheimer's disease

Inclusion criteria:

  • Individuals of either sex, 50-90 years of age.
  • Meeting research criteria for AD (McKhann, Knopman et al. 2011).
  • With a CDR (Morris 1993) score of 1-3.
  • Fluent in English or Spanish.
  • Have sufficient communication and comprehension ability to consent to the performance of the study or have a legally authorized representative.

Exclusion criteria:

  • Inability to undergo MRI or PET for any reason, including severe claustrophobia.
  • History of large stroke or brain trauma, multiple sclerosis or other brain disorder that, in the judgment of the PI may confound the study.
  • Pregnancy. In women in whom the possibility of pregnancy cannot be excluded, a pregnancy test must be performed on site the morning of any PET visit and a negative result together with a physician interview are required prior to the administration or any radiopharmaceutical.
  • Research radiation exposure greater than 50 mSv effective dose within 12 months including radiation exposure from this study.

Healthy volunteers:

Inclusion criteria:

  • Individuals of 18-90 years of age.
  • Negative amyloid accumulation determined by PET (only for the comparison with AD).
  • Fluent in English.
  • Have enough communication and comprehension ability to consent to the performance of the study.

Exclusion criteria:

  • Inability to undergo MRI or PET for any reason, including severe claustrophobia.
  • Brain disorder, other than idiopathic headache.
  • Current primary Axis I or II psychiatric disorder.
  • Current use of psychotropic or anti-epileptic medication.
  • Substance abuse during the past two years.
  • Active cancer, metabolic encephalopathy, infection, cardiovascular disease.
  • Active hematological, renal, pulmonary, endocrine or hepatic disorders, except for treated thyroid disease.
  • Pregnancy. In women in whom the possibility of pregnancy cannot be excluded, a pregnancy test must be performed on site the morning of any PET visit and a negative result together with a physician interview are required prior to the administration or any radiopharmaceutical
  • Research radiation exposure greater than 50 mSv effective dose within 12 months including radiation exposure from this study.
  • Only for the subjects undergoing the blocked scan with selegiline: known contraindications to selegiline, including hypersensitivity to the drug and use of opioids, such as meperidine and some antidepressants such as bupropion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Other

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Healthy subjects
Drug: Positron Emission Tomography (PET) using 11C-ER176 for TSPO and 18F-SMBT1 for MAO-B
Participants will receive PET with 11C-ER176 to measure microglia AND astrocytes and PET with 18F-SMBT1 to measure astrocytes.
Patients with Alzheimer's disease
Drug: Positron Emission Tomography (PET) using 11C-ER176 for TSPO and 18F-SMBT1 for MAO-B
Participants will receive PET with 11C-ER176 to measure microglia AND astrocytes and PET with 18F-SMBT1 to measure astrocytes.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The level of monoamine oxidase-B
Time Frame: At the time of the PET scan
Binding of PET tracer [F-18]SMBT-1 to monoamine oxidase-B
At the time of the PET scan
The level of translocator protein
Time Frame: At the time of the PET scan
Binding of PET tracer [C-11]ER176 to translocator protein
At the time of the PET scan

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Methodist Hospital Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 20, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 7, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 17, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRO00030631

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

It is complex to share IPD in our regulatory environment.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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