DementiaPhase 1NCT03958630
PET Imaging of Neuroinflammation in Neurodegenerative Diseases Via a Novel Translocator Protein (TSPO) Radioligand
A Phase 1 study testing 11C-ER176, 11C-PIB and Positron Emission Tomography (PET) Scan in people with Dementia, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Dementia
- What is being tested?
- 11C-ER176, 11C-PIB and Positron Emission Tomography (PET) Scan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jul 2019to 4 Dec 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 1. 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
- 2. Subjects with an increased risk of neurodegenerative diseases will be included if they
- Are age 18 or older
Show all 14Show fewer
- 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
- 3. 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)
Who cannot join
- 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
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- 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
- Participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use impairs function
- 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
- Are pregnant or breastfeeding
- Participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use impairs function
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: PET Imaging of Neuroinflammation in Neurodegenerative Diseases Via a Novel TSPO Radioligand
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.
Read more
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.
Read the detailed description
Objectives
The primary objective is to explore if human subjects with neurodegenerative diseases exhibit different level of neuroinflammation, as measured by brain uptake of a 3rd generation [11C]ER176 TSPO ligand, compared to control subjects. The secondary objectives are to determine, 1) if [11C]ER176 TSPO brain uptake shows disease-specific patterns across different neurodegenerative diseases and/or genetic mutations, and 2) if longitudinal imaging of individual patients shows a correlation between interval change of tracer uptake and disease progression.
Study population
Adults referred with a clinical diagnosis or with an increased risk of frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer s disease, other related adult-onset neurodegenerative disorders, or healthy control subjects.
Design
Participants will undergo a general and neurological exam, a standard battery of neuropsychological tests to measure cognitive function, blood tests for analysis of TSPO polymorphisms, MRI of the brain, and PET imaging with the [11C]ER176 TSPO radioligand and [11C]PIB amyloid radioligand. Participants will be invited to return for repeat evaluations approximately 1, 2, and 3-5 years after their initial evaluation.
Outcome measures
Brain PET and MRI scans will be co-registered for anatomic definition of regions of interest, and standard uptake value (SUV) will be calculated in various brain regions. [11C]ER176 PET data will be analyzed with compartmental modeling. [11C]PIB PET and MRI data will be adjunctly used for segregating the collected data by disease subtype. For the primary objective, we will compare TSPO radioligand uptake of healthy controls compared to subjects with neurodegenerative diseases. For secondary objectives, we will determine if neuroanatomical regions of tracer uptake differ across different neurodegenerative disease subtypes, and if interval change of tracer uptake correlates with disease progression in longitudinal imaging of individual subjects.
- Conditions
- Dementia
- Being tested
- 11C-ER176, 11C-PIB, Positron Emission Tomography (PET) Scan
- Keywords
- Fronto Temporal Dementia, Amyloid, Neuroinflammation
- Medical subject headings
- Dementia, Alzheimer Disease, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
11C-ER176Drug
PET biomarker for inflammation
11C-PIBDrug
PET biomarker for amyloid
Positron Emission Tomography (PET) ScanDiagnostic test
Participants underwent PET scan with [11C]ER176 and/or 11C-PIB
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: 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) Receives: Drug: 11C-ER176; Drug: 11C-PIB; Diagnostic Test: Positron Emission Tomography (PET) Scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 90 minutes during scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2019
- Study start3 Jul 2019
- Primary completion27 May 2021
- Study completion4 Dec 2023
Why it stopped: PI closed the protocol due to low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DementiaStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert B Innis, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03958630
- Sponsor's protocol ID
- 190095
- Other IDs
- 19-M-0095
- Status last verified
- Jan 2024
- First submitted
- 21 May 2019
- Last updated
- 1 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PET Imaging of Neuroinflammation in Neurodegenerative Diseases Via a Novel TSPO Radioligand
- ClinicalTrials.gov ID
- NCT03958630
- Acronym / sponsor ID
- 190095
- Conditions
- Dementia
- Keywords
- Fronto Temporal Dementia, Amyloid, Neuroinflammation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI closed the protocol due to low recruitment
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 3 Jul 2019 (actual)
- Primary completion
- 27 May 2021 (actual)
- Study completion
- 4 Dec 2023 (actual)
- First posted
- 22 May 2019 (actual)
- Results
- Posted 1 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Objectives
The primary objective is to explore if human subjects with neurodegenerative diseases exhibit different level of neuroinflammation, as measured by brain uptake of a 3rd generation [11C]ER176 TSPO ligand, compared to control subjects. The secondary objectives are to determine, 1) if [11C]ER176 TSPO brain uptake shows disease-specific patterns across different neurodegenerative diseases and/or genetic mutations, and 2) if longitudinal imaging of individual patients shows a correlation between interval change of tracer uptake and disease progression.
Study population
Adults referred with a clinical diagnosis or with an increased risk of frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer s disease, other related adult-onset neurodegenerative disorders, or healthy control subjects.
Design
Participants will undergo a general and neurological exam, a standard battery of neuropsychological tests to measure cognitive function, blood tests for analysis of TSPO polymorphisms, MRI of the brain, and PET imaging with the [11C]ER176 TSPO radioligand and [11C]PIB amyloid radioligand. Participants will be invited to return for repeat evaluations approximately 1, 2, and 3-5 years after their initial evaluation.
Outcome measures
Brain PET and MRI scans will be co-registered for anatomic definition of regions of interest, and standard uptake value (SUV) will be calculated in various brain regions. [11C]ER176 PET data will be analyzed with compartmental modeling. [11C]PIB PET and MRI data will be adjunctly used for segregating the collected data by disease subtype. For the primary objective, we will compare TSPO radioligand uptake of healthy controls compared to subjects with neurodegenerative diseases. For secondary objectives, we will determine if neuroanatomical regions of tracer uptake differ across different neurodegenerative disease subtypes, and if interval change of tracer uptake correlates with disease progression in longitudinal imaging of individual subjects.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers | Experimental | Drug: 11C-ER176, Drug: 11C-PIB, Diagnostic Test: Positron Emission Tomography (PET) ScanParticipants underwent brain positron emission tomography (PET) scan with [11C]ER176 and/or [11C]PIB followed by brain magnetic resonance imaging (MRI) |
| Subjects with chromosome 9 open reading frame 72 (C9ORF72) | Experimental | Drug: 11C-ER176, Drug: 11C-PIB, Diagnostic Test: Positron Emission Tomography (PET) ScanParticipants underwent brain positron emission tomography (PET) scan with [11C]ER176 and/or [11C]PIB followed by brain magnetic resonance imaging (MRI) |
| Subjects with Frontotemporal dementia (FTD) | Experimental | Drug: 11C-ER176, Drug: 11C-PIB, Diagnostic Test: Positron Emission Tomography (PET) ScanParticipants underwent brain positron emission tomography (PET) scan with [11C]ER176 and/or [11C]PiB followed by brain magnetic resonance imaging (MRI) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 1. Patients will be included if they
- Are age 18 or older
- 2. Subjects with an increased risk of neurodegenerative diseases will be included if they
- 3. Healthy subjects will be included if they
Key exclusion criteria (20 listed)
- Patients or subjects with an increased risk of neurodegenerative diseases will be excluded if they
- Healthy subjects will be excluded if they
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 11C-ER176PET biomarker for inflammation | Drug | Healthy volunteers, Subjects with Frontotemporal dementia (FTD), Subjects with chromosome 9 open reading frame 72 (C9ORF72) |
| 11C-PIBPET biomarker for amyloid | Drug | Healthy volunteers, Subjects with Frontotemporal dementia (FTD), Subjects with chromosome 9 open reading frame 72 (C9ORF72) |
| Positron Emission Tomography (PET) ScanParticipants underwent PET scan with [11C]ER176 and/or 11C-PIB | Diagnostic test | Healthy volunteers, Subjects with Frontotemporal dementia (FTD), Subjects with chromosome 9 open reading frame 72 (C9ORF72) |
Primary outcome
Standard Uptake Value Ratio Compared to the Cerebellum (SUVR) Area Under the Curve (AUC) (60-90min)
Time frame: Up to 90 minutes during scan
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert B Innis, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 11C-ER176, 11C-PIB and Positron Emission Tomography (PET) Scan in people with Dementia, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Standard Uptake Value Ratio Compared to the Cerebellum (SUVR) Area Under the Curve (AUC) (60-90min) (time frame: Up to 90 minutes during scan). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2024.