ALSPhase 1NCT04490096
Multimodal Imaging Outcome Measures for ALS (Image ALS)
A Phase 1 study testing [11C]-PBR28 in people with ALS, run by University of Pennsylvania at 1 site in United States.
Trial summary
The primary aim of this study is to determine whether longitudinal neuroimaging acquired across multiple research and clinical centers is a feasible biomarker to use as an outcome measure for clinical trials in amyotrophic lateral sclerosis (ALS) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ALS
- What is being tested?
- [11C]-PBR28
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2021to 17 Mar 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Females who are pregnant at the time of study visits will not be eligible for the PET sub-study; urine or serum pregnancy test will be performed in women of child-bearing potential at each of the baseline, 3-month, and 6-month study visit.
- Homozygous genotype for the threonine-associated substitution allele (A) in the rs6971 polymorphism.
- Blood glucose less than or equal to 250 mg/dl, or at the discretion of the authorized user
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
The primary aim of this study is to determine whether longitudinal neuroimaging acquired across multiple research and clinical centers is a feasible biomarker to use as an outcome measure for clinical trials in amyotrophic lateral sclerosis (ALS)
Read the detailed description
ALS is a progressive neurodegenerative disorder that manifests with extensive clinical heterogeneity, including variable degrees of upper motor neuron (UMN) and lower motor neuron (LMN) impairment. While ALS is classically defined as a neuromuscular disorder, approximately 15% of individuals also develop cognitive and/or behavioral dysfunction of the frontotemporal variety, ranging in severity from ALS with cognitive or behavior impairment to a frank form of dementia consistent with FTD2
- Recent consensus criteria capture this heterogeneity by defining these conditions together as amyotrophic lateral sclerosis frontotemporal spectrum disorder (ALS-FTSD)3
- There are emerging and in-progress interventional clinical trials underway that aim to arrest ALS and/or FTD disease progression; however, there are limited objective and quantitative biomarkers to directly track disease progression during life. Multi-modal neuroimaging provides an ideal candidate biomarker for clinical trials because ALS-FTSD affects a distributed neuroanatomic network and we can reliably measure neurodegeneration of grey matter (GM) and arterial spin labeling based perfusion MRI (pMRI) measurements of cerebral blood flow (CBF). However, there are many unaddressed technical challenges associated with measuring disease progression using neuroimaging techniques in a multi-center setting. The overall aim of this protocol is to leverage a team science approach to develop disease-specific candidate neuroimaging outcome measures for ALS-FTSD clinical trials.
- Conditions
- ALS
- Being tested
- [11C]-PBR28
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[11C]-PBR28Drug
A dose of ≤ 20 mCi (approximate range for most studies is anticipated to be 5-20 mCi) of [11C]-PBR28 will be administered by IV injection to the patient under the direct supervision of a Nuclear Medicine Authorized User. A lesser activity may be injected if, in the opinion of a nuclear medicine authorized user complete imaging data could be generated.
Subjects will undergo an approximately 90 minute dynamic PET/CT scan over the brain starting at approximately the same time as the [11C]-PBR-28 injection. Scans will be acquired using a Philips PET/CT time-of-flight Ingenuity scanner (Philips Healthcare, Cleveland, OH, USA). At the end of the dynamic imaging the participant will be allowed to get off the scanner.
| Study group | Role | What they receive |
|---|---|---|
| [11C]-PBR28 ALS | Other | Neuroinflammatory pathways have been implicated in a variety of neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), but the vast majority of this evidence is from animal or ex vivo human studies. In vivo measurement of the 18 kDa translocator protein (TSPO) has become possible with [11C]-PBR28 PET imaging. Briefly, TSPO expression is increased when microglial are activated. Cross-sectional studies have demonstrated that [11C]-PBR28 uptake is elevated in ALS compared to controls, is correlated with upper motor neuron severity, and that microglial activation is associated with more severe upper motor neuron disease and faster disease progression. We are only aware of a single 6-month study of 10 patients evaluating longitudinal change of [11C]-PBR28 in ALS. We hypothesize that we will observe increased [11C]-PBR28 uptake over a 6-month period in motor cortex and prefrontal cortex in ALS. This portion of the study will be performed at UPenn only. Receives: Drug: [11C]-PBR28 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volume measurement (cubic mm) of brain regions using MRI
Volume measurement (cubic mm) of brain regions using MRI for ALS patients and healthy controls.
Measured: Change from baseline volume measurement (cubic mm) at 6 months
Volume measurement (cubic mm) of brain regions using MRI
Volume measurement (cubic mm) of brain regions using MRI for ALS patients and healthy controls.
Measured: Change from baseline volume measurement (cubic mm) at 12 months
Thickness measurement (mm) of brain regions using MRI
Thickness measurement (mm) of brain regions using MRI in ALS patients and healthy controls.
Measured: Change from baseline thickness measurement (mm) at 6 months
Thickness measurement (mm) of brain regions using MRI
Thickness measurement (mm) of brain regions using MRI in ALS patients and healthy controls.
Measured: Change from baseline thickness measurement (mm) at 12 months
Cerebral blood flow measurement (mL of blood/100g per minute) of brain regions using MRI
Determine whether MRI is a feasible for measuring longitudinal change comparing ALS patients relative to healthy controls. ALS will have increased rate of hyperperfusion, reflected by reduced cerebral blood flow (mL of blood/100g per minute), in the motor cortex and frontal cortex brain regions relative to healthy controls.
Measured: Change from baseline cerebral blood flow measurement (mL of blood/100g per minute) at 6 months
Cerebral blood flow measurement (mL of blood/100g per minute) of brain regions using MRI
Determine whether MRI is a feasible for measuring longitudinal change comparing ALS patients relative to healthy controls. ALS will have increased rate of hyperperfusion, reflected by reduced cerebral blood flow (mL of blood/100g per minute), in the motor cortex and frontal cortex brain regions relative to healthy controls.
Measured: Change from baseline cerebral blood flow measurement (mL of blood/100g per minute at 12 months
Secondary outcomes (4)
[18F]-FDG signal measurement (standard uptake volume or SUV) in brain regions using PET scan
[18F]-FDG signal measurement (Standard Uptake Value or SUV) of [18F]-FDG PET for ALS patients at PENN only.
Measured: Change from baseline [18F]-FDG signal measurement (standard uptake volume or SUV) at 3 months
[18F]-FDG signal measurement (standard uptake volume or SUV) in brain regions using PET scan
[18F]-FDG signal measurement (Standard Uptake Value or SUV) of [18F]-FDG PET for ALS patients at PENN only.
Measured: Change from baseline [18F]-FDG signal measurement (standard uptake volume or SUV) at 6 months
[11C]-PBR28 signal measurement (standard uptake volume or SUV) in brain regions using PET scan
[11C]-PBR28 signal measurement (Standard Uptake Value or SUV) of [11C]-PBR28 PET for ALS patients at PENN only.
Measured: Change from baseline [11C]-PBR28 signal measurement (standard uptake volume or SUV) at 3 months
[11C]-PBR28 signal measurement (standard uptake volume or SUV) in brain regions using PET scan
[11C]-PBR28 signal measurement (Standard Uptake Value or SUV) of [11C]-PBR28 PET for ALS patients at PENN only.
Measured: Change from baseline [11C]-PBR28 signal measurement (standard uptake volume or SUV) at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2020
- Study start25 Feb 2021
- Primary completion17 Mar 2022
- Study completion17 Mar 2022
Why it stopped: Funding issues.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALSStudies 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 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Biogen, University of Miami, University of Kansas
- Responsible party
- Sponsor
- Investigators
- Corey McMillan, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04490096
- Sponsor's protocol ID
- 834366
- Status last verified
- Apr 2022
- First submitted
- 24 Jun 2020
- Last updated
- 12 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multimodal Imaging Outcome Measures for ALS (Image ALS)
- ClinicalTrials.gov ID
- NCT04490096
- Acronym / sponsor ID
- 834366
- Conditions
- ALS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding issues.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Biogen, University of Miami, University of Kansas
- Study start
- 25 Feb 2021 (actual)
- Primary completion
- 17 Mar 2022 (actual)
- Study completion
- 17 Mar 2022 (actual)
- First posted
- 28 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary aim of this study is to determine whether longitudinal neuroimaging acquired across multiple research and clinical centers is a feasible biomarker to use as an outcome measure for clinical trials in amyotrophic lateral sclerosis (ALS)
Detailed description
ALS is a progressive neurodegenerative disorder that manifests with extensive clinical heterogeneity, including variable degrees of upper motor neuron (UMN) and lower motor neuron (LMN) impairment. While ALS is classically defined as a neuromuscular disorder, approximately 15% of individuals also develop cognitive and/or behavioral dysfunction of the frontotemporal variety, ranging in severity from ALS with cognitive or behavior impairment to a frank form of dementia consistent with FTD2
- Recent consensus criteria capture this heterogeneity by defining these conditions together as amyotrophic lateral sclerosis frontotemporal spectrum disorder (ALS-FTSD)3
- There are emerging and in-progress interventional clinical trials underway that aim to arrest ALS and/or FTD disease progression; however, there are limited objective and quantitative biomarkers to directly track disease progression during life. Multi-modal neuroimaging provides an ideal candidate biomarker for clinical trials because ALS-FTSD affects a distributed neuroanatomic network and we can reliably measure neurodegeneration of grey matter (GM) and arterial spin labeling based perfusion MRI (pMRI) measurements of cerebral blood flow (CBF). However, there are many unaddressed technical challenges associated with measuring disease progression using neuroimaging techniques in a multi-center setting. The overall aim of this protocol is to leverage a team science approach to develop disease-specific candidate neuroimaging outcome measures for ALS-FTSD clinical trials.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [11C]-PBR28 ALS | Other | Drug: [11C]-PBR28Neuroinflammatory pathways have been implicated in a variety of neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), but the vast majority of this evidence is from animal or ex vivo human studies. In vivo measurement of the 18 kDa translocator protein (TSPO) has become possible with [11C]-PBR28 PET imaging. Briefly, TSPO expression is increased when microglial are activated. Cross-sectional studies have demonstrated that [11C]-PBR28 uptake is elevated in ALS compared to controls, is correlated with upper motor neuron severity, and that microglial activation is associated with more severe upper motor neuron disease and faster disease progression. We are only aware of a single 6-month study of 10 patients evaluating longitudinal change of [11C]-PBR28 in ALS. We hypothesize that we will observe increased [11C]-PBR28 uptake over a 6-month period in motor cortex and prefrontal cortex in ALS. This portion of the study will be performed at UPenn only. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (3 listed)
- Females who are pregnant at the time of study visits will not be eligible for the PET sub-study; urine or serum pregnancy test will be performed in women of child-bearing potential at each of the baseline, 3-month, and 6-month study visit.
- Homozygous genotype for the threonine-associated substitution allele (A) in the rs6971 polymorphism.
- Blood glucose less than or equal to 250 mg/dl, or at the discretion of the authorized user
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]-PBR28A dose of ≤ 20 mCi (approximate range for most studies is anticipated to be 5-20 mCi) of [11C]-PBR28 will be administered by IV injection to the patient under the direct supervision of a Nuclear Medicine Authorized User. A lesser activity may be injected if, in the opinion of a nuclear medicine authorized user complete imaging data could be generated. Subjects will undergo an approximately 90 minute dynamic PET/CT scan over the brain starting at approximately the same time as the [11C]-PBR-28 injection. Scans will be acquired using a Philips PET/CT time-of-flight Ingenuity scanner (Philips Healthcare, Cleveland, OH, USA). At the end of the dynamic imaging the participant will be allowed to get off the scanner. | Drug | [11C]-PBR28 ALS |
Primary outcome
Volume measurement (cubic mm) of brain regions using MRI
Time frame: Change from baseline volume measurement (cubic mm) at 6 months
Volume measurement (cubic mm) of brain regions using MRI for ALS patients and healthy controls.
Volume measurement (cubic mm) of brain regions using MRI
Time frame: Change from baseline volume measurement (cubic mm) at 12 months
Volume measurement (cubic mm) of brain regions using MRI for ALS patients and healthy controls.
Thickness measurement (mm) of brain regions using MRI
Time frame: Change from baseline thickness measurement (mm) at 6 months
Thickness measurement (mm) of brain regions using MRI in ALS patients and healthy controls.
Thickness measurement (mm) of brain regions using MRI
Time frame: Change from baseline thickness measurement (mm) at 12 months
Thickness measurement (mm) of brain regions using MRI in ALS patients and healthy controls.
Cerebral blood flow measurement (mL of blood/100g per minute) of brain regions using MRI
Time frame: Change from baseline cerebral blood flow measurement (mL of blood/100g per minute) at 6 months
Determine whether MRI is a feasible for measuring longitudinal change comparing ALS patients relative to healthy controls. ALS will have increased rate of hyperperfusion, reflected by reduced cerebral blood flow (mL of blood/100g per minute), in the motor cortex and frontal cortex brain regions relative to healthy controls.
Cerebral blood flow measurement (mL of blood/100g per minute) of brain regions using MRI
Time frame: Change from baseline cerebral blood flow measurement (mL of blood/100g per minute at 12 months
Determine whether MRI is a feasible for measuring longitudinal change comparing ALS patients relative to healthy controls. ALS will have increased rate of hyperperfusion, reflected by reduced cerebral blood flow (mL of blood/100g per minute), in the motor cortex and frontal cortex brain regions relative to healthy controls.
4 secondary outcomes
[18F]-FDG signal measurement (standard uptake volume or SUV) in brain regions using PET scan
Time frame: Change from baseline [18F]-FDG signal measurement (standard uptake volume or SUV) at 3 months
[18F]-FDG signal measurement (standard uptake volume or SUV) in brain regions using PET scan
Time frame: Change from baseline [18F]-FDG signal measurement (standard uptake volume or SUV) at 6 months
[11C]-PBR28 signal measurement (standard uptake volume or SUV) in brain regions using PET scan
Time frame: Change from baseline [11C]-PBR28 signal measurement (standard uptake volume or SUV) at 3 months
[11C]-PBR28 signal measurement (standard uptake volume or SUV) in brain regions using PET scan
Time frame: Change from baseline [11C]-PBR28 signal measurement (standard uptake volume or SUV) at 6 months
Results and safety
The study was stopped early (reason given: Funding issues.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2022.
- Individual participant dataSharing planned: No
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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.
Corey McMillan, PhD 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 1 study testing [11C]-PBR28 in people with ALS, 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 0 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 12 Apr 2022. 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?
The study was stopped early (reason given: Funding issues.). Results are not available in the source record.
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?
Volume measurement (cubic mm) of brain regions using MRI (time frame: Change from baseline volume measurement (cubic mm) at 6 months). The study lists 6 primary outcomes in all. 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 12 Apr 2022.