Evaluation of Microglial Activation in ALS With [18F]PBR06 (Peripheral Benzodiazepine Receptor-06) PET

NCT03876002 | Completed Phase 1 FDA Drug

• 1 other identifier: [18F]PBR06
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Healthy Volunteers; Amyotrophic Lateral Sclerosis

Keywords

HV; ALS

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year

Study Arms (1)

[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.

Drug: [18F]PBR06

Interventions

[18F]PBR06 DRUG

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).

[18F]PBR06

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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".
• 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.
• 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.

Sponsors & Collaborators

• Molecular NeuroImaging: lead

Study Sites (1)

Molecular NeuroImaging, LLC

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• David Russell, M.D., Ph. D

  Molecular NeuroImaging

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 15, 2019
• Study Start: June 28, 2016
• Primary Completion: February 7, 2018
• Study Completion: February 7, 2018
• Last Updated: March 26, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will become available beginning 3 months and ending 5 years article publication.
• Access Criteria: 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.

Locations

US (1)