PET Imaging of Neuroinflammation in Neurodegenerative Diseases Via a Novel Translocator Protein (TSPO) Radioligand

NCT03958630 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 19009519-M-0095
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Aging-related progressive neurological disorders include frontotemporal dementia, Lou Gehrig s disease, and Alzheimer s disease. Little is known about what causes these disorders. Brain inflammation may be involved. Researchers want to see if scans using radioactive drugs can show brain inflammation. Objective: To see if the drug \[11C\]ER176 can show inflammation in the brain in people with certain progressive neurological disorders compared to healthy adults. Also to find genes that might be associated with or cause these disorders. Eligibility: People ages 18 and older with an aging-related neurological disorder, and healthy adults Design: Participants will be screened with a medical history, physical exam, neurological exam, psychiatric history, and blood tests. Participants will have 2-5 visits for the first session. They will have 2 PET scans and 1 MRI scan. They may have 3 more sessions: 6 months to about 18 months later, 1 year after that, and about 30 months to 5 years after the first visit. There may be up to 20 total visits. For the scans, participants will lie on a bed that slides into the scanners. For the PET scans, a strap will fix their head in place. A radioactive drug will be injected through a catheter. A needle will guide a thin plastic tube into an arm vein. Additional catheters may be put in place to draw blood. Each PET will take 2 hours. The MRI will take 30 60 minutes. At each session, participants will have a brief interview, medical history, physical exam, blood and urine tests, heart tests, and memory and thinking tests. They may donate blood for DNA tests.

Conditions

Dementia

Keywords

Fronto Temporal Dementia; Amyloid; Neuroinflammation

Outcome Measures

Primary Outcomes (1)

• Standard Uptake Value Ratio Compared to the Cerebellum (SUVR) Area Under the Curve (AUC) (60-90min)

  Participants underwent brain positron emission tomography (PET) scan with \[11C\]ER176 and standard uptake value (SUV) was measured over 90 minutes and divided by SUV of the cerebellum to determine difference of \[11C\]ER176 brain uptake

  Up to 90 minutes during scan

Study Arms (3)

Healthy volunteers

EXPERIMENTAL

Participants underwent brain positron emission tomography (PET) scan with \[11C\]ER176 and/or \[11C\]PIB followed by brain magnetic resonance imaging (MRI)

Drug: 11C-ER176; Drug: 11C-PIB; Diagnostic Test: Positron Emission Tomography (PET) Scan

Subjects with chromosome 9 open reading frame 72 (C9ORF72)

EXPERIMENTAL

Participants underwent brain positron emission tomography (PET) scan with \[11C\]ER176 and/or \[11C\]PIB followed by brain magnetic resonance imaging (MRI)

Drug: 11C-ER176; Drug: 11C-PIB; Diagnostic Test: Positron Emission Tomography (PET) Scan

Subjects with Frontotemporal dementia (FTD)

EXPERIMENTAL

Participants underwent brain positron emission tomography (PET) scan with \[11C\]ER176 and/or \[11C\]PiB followed by brain magnetic resonance imaging (MRI)

Drug: 11C-ER176; Drug: 11C-PIB; Diagnostic Test: Positron Emission Tomography (PET) Scan

Interventions

11C-ER176 DRUG

PET biomarker for inflammation

Healthy volunteers; Subjects with Frontotemporal dementia (FTD); Subjects with chromosome 9 open reading frame 72 (C9ORF72)

11C-PIB DRUG

PET biomarker for amyloid

Healthy volunteers; Subjects with Frontotemporal dementia (FTD); Subjects with chromosome 9 open reading frame 72 (C9ORF72)

Positron Emission Tomography (PET) Scan DIAGNOSTIC_TEST

Participants underwent PET scan with \[11C\]ER176 and/or 11C-PIB

Healthy volunteers; Subjects with Frontotemporal dementia (FTD); Subjects with chromosome 9 open reading frame 72 (C9ORF72)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients will be included if they
• Are age 18 or older
• Have the ability to understand and sign an informed consent, or have a DPA or a court-appointed guardian (or be able to understand the DPA process to appoint a DPA) to provide consent for adults without consent capacity
• Have been given a diagnosis by a neurologist of frontotemporal dementia, frontotemporal lobar degeneration, primary progressive aphasia, semantic dementia, motor neuron disorder, amyotrophic lateral sclerosis, primary lateral sclerosis, progressive bulbar palsy, corticobasal syndrome, Huntington disease, Alzheimer s disease, or other related adult-onset neurodegenerative disease
• \. Subjects with an increased risk of neurodegenerative diseases will be included if they
• Are age 18 or older
• Are able to give written informed consent
• Have known family history or other risk of an adult-onset genetic neurodegenerative disease, and/or mutation in a gene known to cause an adult-onset neurodegenerative disease
• \. Healthy subjects will be included if they
• Are age 18 or older
• Are willing and able to complete all study procedures
• Are able to give written informed consent
• Are medically healthy
• Are enrolled in 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers (PI: Dr. Carlos Zarate) or 17-M-0181, Recruitment and Characterization of Healthy Research Volunteers for National Institute of Mental Health (NIMH) Intramural Studies (PI: Dr. Joyce Chung)

You may not qualify if:

• Patients or subjects with an increased risk of neurodegenerative diseases will be excluded if they
• Have other major neurological or medical diseases that may cause progressive weakness or cognitive dysfunction, such as structural brain or spinal cord disease, metabolic diseases, paraneoplastic syndromes, infectious diseases, peripheral neuropathy or radiculopathy or other significant neurological abnormalities
• Have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., active infection or untreated malignancy)
• Require daytime ventilator support at the time of study entry
• Are unable to travel to NIH
• Have recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits
• Have inability to lie flat and/or lie still on camera bed for at least two hours, including claustrophobia, overweight greater than the maximum for the scanner, and uncontrollable behavioral symptoms, which will be screened by an interview with patient and/or caregiver during the screening visit
• Are pregnant or breastfeeding
• Are unable to have an MRI scan (e.g., pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, or shrapnel fragments, metal fragments in the eye)
• NIMH employees/staffs or NIH employees who are subordinates/relatives/co-workers of investigators
• Healthy subjects will be excluded if they
• Have any history of medical illness or injury with the potential to affect study data interpretation or to be any medical contraindication to the procedures performed in the study, including active infection and untreated malignancy.
• Have clinically significant laboratory abnormalities based on test performed under screening protocol 01-M-0254 or 17-M-0181
• Have recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits
• Have inability to lie flat on camera bed for at least two hours, including claustrophobia and overweight greater than the maximum for the scanner

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Dementia; Alzheimer Disease; Neuroinflammatory Diseases

Interventions

2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; Positron-Emission Tomography; Radionuclide Imaging

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Image Enhancement; Photography; Tomography; Diagnostic Techniques, Radioisotope

Limitations and Caveats

Secondary outcomes were not analyzed because: * No data for the disease specific uptake across neurodegenerative diseases * No longitudinal data was collected because the protocol was terminated due to low recruitment

Results Point of Contact

• Title: Innis, Robert
• Organization: National Institute of Mental Health

robert.innis@nih.gov

+1 301 594 1368

Study Officials

• Robert B Innis, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 22, 2019
• Study Start: July 3, 2019
• Primary Completion: May 27, 2021
• Study Completion: December 4, 2023
• Last Updated: May 1, 2024
• Results First Posted: May 1, 2024

Record last verified: 2024-01

Locations

US (1)