Mild Cognitive ImpairmentPhase 2NCT02811744
11C-Acetate PET/CT Imaging As a Biomarker of Amyloid-Induced Neuroinflammation
A Phase 2 study testing 11C-acetate in people with Mild Cognitive Impairment, run by University of Pennsylvania at 1 site in United States.
Trial summary
The proposed study aims to use 11C-acetate position emission tomography/computed tomography (PET/CT) to preliminarily test and validate methods for imaging astrocyte activation as an early indicator of neuroinflammation in Alzheimer's disease (AD). Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- 11C-acetate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to 28 Feb 2022
- Phase
- Phase 2
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Participants will be at least 65 years of age
- Positive brain amyloid PET/CT scan within 6 months of study screening
- Mini-mental status examination (MMSE) score ≥ 24 at screening visit
- A brain MRI is required. If a brain MRI has been performed within 6 months of 11C-Acetate PET/CT and of adequate quality that scan may be used for the study analysis, subjects who do not have a brain MRI will undergo a brain MRI as a part of this study
- Participants must identify a study partner who is willing to accompany the patient to study visits
- Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures. If the patient is unable to provide informed consent, the patient's legal representative may consent on behalf of the patient but the patient will be asked to confirm assent.
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- Participants will be at least 65 years of age
- History of negative brain amyloid PET/CT scan within 6 months of study screening OR negative cerebrospinal fluid (CSF) analysis for AD biomarkers within 6 months of study screening
- Mini-mental status examination (MMSE) > 27 at screening visit
- A brain MRI is required. If a brain MRI has been performed within 6 months of enrollment to this study and of adequate quality that scan may be used for the study analysis, subjects who do not have a brain MRI will undergo a brain MRI as a part of this study
- Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures.
Who cannot join
- Inability to tolerate or contraindication to imaging procedures (PET/CT or MRI) in the opinion of an investigator or treating physician
- History of stroke or other neurological disease that in the opinion of the investigator might interfere with evaluation of the 11C-Acetate scan
- Any medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: 11C-Acetate Position Emission Tomography/Computerized Tomography (PET/CT) Imaging As a Biomarker of Amyloid-Induced Neuroinflammation
The proposed study aims to use 11C-acetate position emission tomography/computed tomography (PET/CT) to preliminarily test and validate methods for imaging astrocyte activation as an early indicator of neuroinflammation in Alzheimer's disease (AD). 11C-Acetate PET/CT has been shown to quantify astrocyte activation in vivo, but no reports have evaluated its potential in AD. The investigators propose to test 11C-Acetate PET/CT as a marker for astrocyte activation associated with pathologic amyloid deposition in AD. The investigators will compare binding between subjects with early stage AD and healthy controls. Further, the investigators will investigate the correlation between amyloid and acetate binding. If the investigators find increased astrocyte activation in response to cerebral amyloid by showing a group difference in brain acetate uptake between disease and controls or a strong correlation between acetate and amyloid PET/CT binding. Validating neuroinflammation markers in AD ultimately may guide therapeutic modulation of beneficial and damaging neuroinflammation to slow disease progression, as well as providing new insights into AD pathophysiology.
- Conditions
- Mild Cognitive Impairment
- Being tested
- 11C-acetate
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
11C-acetateDrug
Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan.
| Study group | Role | What they receive |
|---|---|---|
| Amnestic MCI cohort | Experimental | Patients with Mild Cognitive Impairment (MCI) (up to 14) will be recruited primarily from the Penn Memory Center (PMC). Clinical diagnostic criteria (described in further detail in Study Procedures section) will be used to identify subjects who are meet criteria for amnestic MCI. Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan. Receives: Drug: 11C-acetate |
| Control cohort | Other | Normal control subjects in the same age range (up to 6) will be recruited from a current ongoing study investigating neuroinflammation in late life depression and healthy controls, from the control group in which all subjects receive MRI and lumbar puncture (LP) and from the PMC research cohort. Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan. Receives: Drug: 11C-acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
11C-acetate Uptake in Amyloid Positive Mild Cognitive Impairment (MCI) Subjects Versus Amyloid Negative Healthy Controls
We compare the whole brain 11C-acetate uptake standardized uptake value ratio (SUVR) between the amnestic MCI and control cohorts. Static summed images from 40-60 minutes after tracer injection were generated from raw dynamic PET data. This timeframe was selected to preferentially capture 11C-acetate trapped in biosynthetic pathways in activated astrocytes, rather than what was catabolized to 11C-CO2 .Mean tracer binding, expressed as standardized uptake values (SUV) in the whole cerebral cortex and other regions is measured from these summed images using PMOD software (PMOD technologies). SUVR is generated by dividing the mean whole cortex SUV by the mean cerebellar gray matter SUV; SUVR is a unitless measure. For this tracer, higher values are worse, indicating more astrocyte activation and inflammation.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2016 (estimated)
- Study startJan 2017
- Primary completion28 Feb 2022
- Study completion28 Feb 2022
Why it stopped: Funding issues.
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 Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ilya Nasrallah, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02811744
- Sponsor's protocol ID
- 824822
- Status last verified
- Jan 2024
- First submitted
- 20 Jun 2016
- Last updated
- 11 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 11C-Acetate Position Emission Tomography/Computerized Tomography (PET/CT) Imaging As a Biomarker of Amyloid-Induced Neuroinflammation
- ClinicalTrials.gov ID
- NCT02811744
- Acronym / sponsor ID
- 824822
- Conditions
- Mild Cognitive Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding issues.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 23 Jun 2016 (estimated)
- Results
- Posted 11 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study aims to use 11C-acetate position emission tomography/computed tomography (PET/CT) to preliminarily test and validate methods for imaging astrocyte activation as an early indicator of neuroinflammation in Alzheimer's disease (AD). 11C-Acetate PET/CT has been shown to quantify astrocyte activation in vivo, but no reports have evaluated its potential in AD. The investigators propose to test 11C-Acetate PET/CT as a marker for astrocyte activation associated with pathologic amyloid deposition in AD. The investigators will compare binding between subjects with early stage AD and healthy controls. Further, the investigators will investigate the correlation between amyloid and acetate binding. If the investigators find increased astrocyte activation in response to cerebral amyloid by showing a group difference in brain acetate uptake between disease and controls or a strong correlation between acetate and amyloid PET/CT binding. Validating neuroinflammation markers in AD ultimately may guide therapeutic modulation of beneficial and damaging neuroinflammation to slow disease progression, as well as providing new insights into AD pathophysiology.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amnestic MCI cohort | Experimental | Drug: 11C-acetatePatients with Mild Cognitive Impairment (MCI) (up to 14) will be recruited primarily from the Penn Memory Center (PMC). Clinical diagnostic criteria (described in further detail in Study Procedures section) will be used to identify subjects who are meet criteria for amnestic MCI. Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan. |
| Control cohort | Other | Drug: 11C-acetateNormal control subjects in the same age range (up to 6) will be recruited from a current ongoing study investigating neuroinflammation in late life depression and healthy controls, from the control group in which all subjects receive MRI and lumbar puncture (LP) and from the PMC research cohort. Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (11 listed)
- Participants will be at least 65 years of age
- Positive brain amyloid PET/CT scan within 6 months of study screening
- Mini-mental status examination (MMSE) score ≥ 24 at screening visit
- A brain MRI is required. If a brain MRI has been performed within 6 months of 11C-Acetate PET/CT and of adequate quality that scan may be used for the study analysis, subjects who do not have a brain MRI will undergo a brain MRI as a part of this study
- Participants must identify a study partner who is willing to accompany the patient to study visits
Key exclusion criteria (3 listed)
- Inability to tolerate or contraindication to imaging procedures (PET/CT or MRI) in the opinion of an investigator or treating physician
- History of stroke or other neurological disease that in the opinion of the investigator might interfere with evaluation of the 11C-Acetate scan
- Any medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.
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-acetateParticipants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan. | Drug | Amnestic MCI cohort, Control cohort |
Primary outcome
11C-acetate Uptake in Amyloid Positive Mild Cognitive Impairment (MCI) Subjects Versus Amyloid Negative Healthy Controls
Time frame: 6 months
We compare the whole brain 11C-acetate uptake standardized uptake value ratio (SUVR) between the amnestic MCI and control cohorts. Static summed images from 40-60 minutes after tracer injection were generated from raw dynamic PET data. This timeframe was selected to preferentially capture 11C-acetate trapped in biosynthetic pathways in activated astrocytes, rather than what was catabolized to 11C-CO2 .Mean tracer binding, expressed as standardized uptake values (SUV) in the whole cerebral cortex and other regions is measured from these summed images using PMOD software (PMOD technologies). SUVR is generated by dividing the mean whole cortex SUV by the mean cerebellar gray matter SUV; SUVR is a unitless measure. For this tracer, higher values are worse, indicating more astrocyte activation and inflammation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Ilya Nasrallah, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 11C-acetate in people with Mild Cognitive Impairment, run by University of Pennsylvania 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 11 inclusion and 3 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 11 Jan 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 11 Jan 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?
11C-acetate Uptake in Amyloid Positive Mild Cognitive Impairment (MCI) Subjects Versus Amyloid Negative Healthy Controls (time frame: 6 months). 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 11 Jan 2024.