Healthy VolunteersPhase 1NCT03876002
Evaluation of Microglial Activation in ALS With [18F]PBR06 (Peripheral Benzodiazepine Receptor-06) PET
A Phase 1 study testing [18F]PBR06 in people with Healthy Volunteers and Amyotrophic Lateral Sclerosis, run by Molecular NeuroImaging at 1 site in United States.
Trial summary
The overall goal of this protocol is to evaluate microglial activation in the brain using [18F]PBR06 in patients with amyotrophic lateral sclerosis (ALS). Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers, Amyotrophic Lateral Sclerosis
- What is being tested?
- [18F]PBR06
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jun 2016to 7 Feb 2018
- 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 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent must be obtained before any assessment is performed.
- Provide signed and dated written informed consent.
- Female subjects must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal ligation) or post-menopausal for at least 1 year or, if they are of child-bearing potential, must commit to the use of a barrier method of contraception for the study duration,
- Male subjects and their partners of childbearing potential must commit to the use of a barrier method of contraception for the study duration.
- Male subjects must not donate sperm for the study duration.
- Able to lie supine on camera bed for a reasonable period of time.
Show all 17Show fewer
- Willing and able to cooperate with study procedures.
- Women of child bearing potential must have a negative pregnancy test at screening.
- Males and females aged 45-80 years, healthy with no clinically relevant finding on physical examination at screening and upon reporting for the [18F]PBR06 imaging sessions.
- No family history of ALS or frontotemporal dementia.
- C-reactive protein level ≤10 mg/dL Inclusion criteria specific to ALS subjects
- Males and females aged 18 to 80 years.
- Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by the modified El Escorial criteria;
- Subjects with a diagnosis of possible ALS must have upper motor neuron (UMN) signs to be eligible
- ALS cognitive behavioral screen score >10 on the cognitive scale and/or >32 on the behavioral scale;
- Forced vital capacity of ≥40%; or if in the opinion of the investigator can lay flat for up to 90 minutes. If an forced vital capacity (FVC) has been performed within the past 6 months; this data may be used at the discretion of the investigator.
- Medications for ALS subjects should be stable for 30 days prior to the Screening Visit and remain unchanged during the subject's participation in the study.
Who cannot join
- Low affinity translocator protein (TSPO) binders determined by having a Thr/Thr polymorphism in the TSPO gene at screening.
- Treatment with immunosuppressive agents (eg. prednisone, solumedrol) within 30 days of baseline and follow-up imaging.Treatment with anti-inflammatory agents including any medications in the following classes of NSAIDS: carboxylic acids, enolic acids, cyclooxygenase (COX) II Inhibitors within 14 days of baseline and follow-up imaging. Treatment with benzodiazepines within 5 half-lives prior to any [18F]PBR06 imaging visit.
- For subjects undergoing arterial line placement, treatment with any antihemostasis medication (e.g., warfarin, heparin, thrombin inhibitors, Factor Xa inhibitors, streptokinase, urokinase, tissue plasminogen activators) within 2 weeks of the planned arterial line placement of either the baseline or follow-up imaging.
- For subjects undergoing arterial line placement, a Modified Allen's test indicating insufficient ulnar artery blood supply to the hand.
- Current or prior history of alcohol or drug abuse.
- Current tobacco use including cigarettes, cigars, and chewing tobacco, or nicotine-containing products such as gum, patch, or "electronic cigarettes".
Show all 15Show fewer
- Positive urine drug screen or urine cotinine screen, with the exception of tetrahydrocannabinol (THC) in ALS subjects for whom medical marijuana is prescribed.
- Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness.
- Subject has received an investigational therapeutic within 30 days prior to screening.
- Radiation exposure over the past year (including prior participation in other research protocols, clinical care or participation in this study) exceeding the effective dose of 50 millisievert (mSv), which would be above the acceptable annual limit established by the US Federal Guidelines.
- Pregnancy, lactating or breastfeeding.
- Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency, pulmonary, or other disorder or disease.
- Unsuitable veins for repeated venipuncture.
- MRI exclusion criteria include: Findings that may interfere with interpretation of the [18F]PBR06 PET imaging, including but not limited to: significant cortical cerebrovascular disease, infectious disease, space-occupying lesions, hydrocephalus or other abnormalities associated with central nervous system (CNS) disease.
- Contraindications to MRI imaging, including but not limited to: Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia, which in the opinion of the investigator is severe and prohibits imaging.
Trial locations and contacts
1 site in 1 country.
United States1 site
Molecular NeuroImaging, LLC
New Haven, Connecticut, 06510
About this study
Official title: Evaluation of Microglial Activation Using the PET Imaging Ligand [18F]PBR06 in Patients With Amyotrophic Lateral Sclerosis Compared to Healthy Volunteers
The overall goal of this protocol is to evaluate microglial activation in the brain using [18F]PBR06 in patients with amyotrophic lateral sclerosis (ALS).
Read the detailed description
The overall goal of this protocol is to evaluate microglial activation in the brain using [18F]PBR06 in patients with amyotrophic lateral sclerosis (ALS). The specific objectives are:
- To measure the dynamic uptake and washout of [18F]PBR06 (Peripheral benzodiazepine receptor-06) in brain using positron emission tomography (PET) in patients with ALS and healthy volunteers (HV).
- To evaluate test/retest reliability of the tracer binding parameters in patients with ALS and HV.
- To evaluate the correlation of [18F]PBR06 binding with ALS disease clinical severity (ALSFRS-R, upper motor neuron burden (UMNB) and Ashworth Score), clinical disease sub-categorization, and other clinical data.
- To perform kinetic modeling using plasma-based (metabolite corrected plasma concentration) or reference region based methods or simplified quantification methods to assess the ability of [18F]PBR06 PET to measure microglial activation in brain.
- To acquire safety data following injection of [18F]PBR06.
- Conditions
- Healthy Volunteers, Amyotrophic Lateral Sclerosis
- Being tested
- [18F]PBR06
- Keywords
- HV, ALS
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]PBR06Drug
Subjects will undergo PET imaging using 1 single intravenous (IV) injection of [18F]PBR06, a PET radioligand for evaluation of microglial activation in the brain. PBR06 will be injected intravenously as a bolus at a dose of no more than 5.5mCi (millicurie).
| Study group | Role | What they receive |
|---|---|---|
| [18F]PBR06 | Experimental | To perform kinetic modeling using plasma-based (metabolite corrected plasma concentration) or reference region based methods or simplified quantification methods to assess the ability of [18F]PBR06 PET to measure microglial activation in brain. Receives: Drug: [18F]PBR06 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time-activity data
Time-activity data will be analyzed with 2-tissue compartment model, using the radiometabolite-corrected plasma input function. To correct the brain data for its vascular component, radioactivity in serial whole blood will be measured and then subtracted from the PET measurements. Non-invasive simple tissue ratio methods will also be evaluated.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2019
- Study start28 Jun 2016
- Primary completion7 Feb 2018
- Study completion7 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Molecular NeuroImaging
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Russell, M.D., Ph. D, Principal investigator, Molecular NeuroImaging
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03876002
- Sponsor's protocol ID
- [18F]PBR06
- Status last verified
- Mar 2019
- First submitted
- 13 Mar 2019
- Last updated
- 26 Mar 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: individual patient data (IPD) that underlie results in any publication will be made accessible for other researchers. All text, tables, figures and appendices will be deidentified. Other documents that will be available include the study protocol, statistical analysis plan, and analytic codes. The data will become available beginning 3 months and ending 5 years article publication via a third-party website (link will be provided). Researchers who provide a methodological sound proposal and aims for intended use of the data will be granted access and will be required to sign a data access agreement. Proposals should be directed to the Study Principal Investigator David Russell, M.D. Ph.D., at david.russell@invicro.com.
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Microglial Activation Using the PET Imaging Ligand [18F]PBR06 in Patients With Amyotrophic Lateral Sclerosis Compared to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03876002
- Acronym / sponsor ID
- [18F]PBR06
- Conditions
- Healthy Volunteers, Amyotrophic Lateral Sclerosis
- Keywords
- HV, ALS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Molecular NeuroImagingUniversity, hospital or other
- Study start
- 28 Jun 2016 (actual)
- Primary completion
- 7 Feb 2018 (actual)
- Study completion
- 7 Feb 2018 (actual)
- First posted
- 15 Mar 2019 (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 overall goal of this protocol is to evaluate microglial activation in the brain using [18F]PBR06 in patients with amyotrophic lateral sclerosis (ALS).
Detailed description
The overall goal of this protocol is to evaluate microglial activation in the brain using [18F]PBR06 in patients with amyotrophic lateral sclerosis (ALS). The specific objectives are:
- To measure the dynamic uptake and washout of [18F]PBR06 (Peripheral benzodiazepine receptor-06) in brain using positron emission tomography (PET) in patients with ALS and healthy volunteers (HV).
- To evaluate test/retest reliability of the tracer binding parameters in patients with ALS and HV.
- To evaluate the correlation of [18F]PBR06 binding with ALS disease clinical severity (ALSFRS-R, upper motor neuron burden (UMNB) and Ashworth Score), clinical disease sub-categorization, and other clinical data.
- To perform kinetic modeling using plasma-based (metabolite corrected plasma concentration) or reference region based methods or simplified quantification methods to assess the ability of [18F]PBR06 PET to measure microglial activation in brain.
- To acquire safety data following injection of [18F]PBR06.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [18F]PBR06 | Experimental | Drug: [18F]PBR06To perform kinetic modeling using plasma-based (metabolite corrected plasma concentration) or reference region based methods or simplified quantification methods to assess the ability of [18F]PBR06 PET to measure microglial activation in brain. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Written informed consent must be obtained before any assessment is performed.
- Provide signed and dated written informed consent.
- Female subjects must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal ligation) or post-menopausal for at least 1 year or, if they are of child-bearing potential, must commit to the use of a barrier method of contraception for the study duration,
- Male subjects and their partners of childbearing potential must commit to the use of a barrier method of contraception for the study duration.
- Male subjects must not donate sperm for the study duration.
Key exclusion criteria (15 listed)
- Low affinity translocator protein (TSPO) binders determined by having a Thr/Thr polymorphism in the TSPO gene at screening.
- Treatment with immunosuppressive agents (eg. prednisone, solumedrol) within 30 days of baseline and follow-up imaging.Treatment with anti-inflammatory agents including any medications in the following classes of NSAIDS: carboxylic acids, enolic acids, cyclooxygenase (COX) II Inhibitors within 14 days of baseline and follow-up imaging. Treatment with benzodiazepines within 5 half-lives prior to any [18F]PBR06 imaging visit.
- For subjects undergoing arterial line placement, treatment with any antihemostasis medication (e.g., warfarin, heparin, thrombin inhibitors, Factor Xa inhibitors, streptokinase, urokinase, tissue plasminogen activators) within 2 weeks of the planned arterial line placement of either the baseline or follow-up imaging.
- For subjects undergoing arterial line placement, a Modified Allen's test indicating insufficient ulnar artery blood supply to the hand.
- Current or prior history of alcohol or drug abuse.
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 |
|---|---|---|
| [18F]PBR06Subjects will undergo PET imaging using 1 single intravenous (IV) injection of [18F]PBR06, a PET radioligand for evaluation of microglial activation in the brain. PBR06 will be injected intravenously as a bolus at a dose of no more than 5.5mCi (millicurie). | Drug | [18F]PBR06 |
Primary outcome
Time-activity data
Time frame: 1 year
Time-activity data will be analyzed with 2-tissue compartment model, using the radiometabolite-corrected plasma input function. To correct the brain data for its vascular component, radioactivity in serial whole blood will be measured and then subtracted from the PET measurements. Non-invasive simple tissue ratio methods will also be evaluated.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
- Individual participant dataSharing planned: Yes. individual patient data (IPD) that underlie results in any publication will be made accessible for other researchers. All text, tables, figures and appendices will be deidentified. Other documents that will be available include the study protocol, statistical analysis plan, and analytic codes. The data will become available beginning 3 months and ending 5 years article publication via a third-party website (link will be provided). Researchers who provide a methodological sound proposal and aims for intended use of the data will be granted access and will be required to sign a data access agreement. Proposals should be directed to the Study Principal Investigator David Russell, M.D. Ph.D., at david.russell@invicro.com.
Related trials for Healthy Volunteers
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
Not yet recruitingObservational study
Screening Protocol
Pain
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.
David Russell, M.D., Ph. D principal investigator
Molecular NeuroImaging
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 [18F]PBR06 in people with Healthy Volunteers and Amyotrophic Lateral Sclerosis, run by Molecular NeuroImaging 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 17 inclusion and 15 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: finished, as of the sponsor's last update on 26 Mar 2019. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Time-activity data (time frame: 1 year). 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 26 Mar 2019.