Imaging [18F]PI-2620 and [18F]Florbetaben in Military Service Members With Blast Related Mild Traumatic Brain Injury

The main objective of this interdisciplinary study is to develop an understanding of the molecular imaging features of blast-related mild traumatic brain injury (mTBI) in military personnel, while helping to establish assessment tools that may be of use in diagnosis, determining prognosis, and in future therapeutic clinical trials. Additionally, the objective is to evaluate feasibility of [18F]PI-2620 in the assessment TBI.

Study Overview

• Status: Active, not recruiting
• Conditions: Mild Traumatic Brain Injury
• Intervention / Treatment: Drug: [18F]PI-2620

Detailed Description

The main objective of this interdisciplinary study is to develop an understanding of the molecular imaging features of blast-related mild traumatic brain injury (mTBI) in military personnel, while helping to establish assessment tools that may be of use in diagnosis, determining prognosis, and in future therapeutic clinical trials. Additionally, the objective is to evaluate feasibility of [18F]PI-2620 in the assessment TBI. This particular tracer has been shown to be effective in localizing tau deposition. [18F]PI-2620 has not yet received FDA approval for routine clinical use and for the purpose of this study is considered an Investigational New Drug (IND) by the FDA.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center (WRNMMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 52 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male
2. Right-handed
3. Age 25-54
4. Agree to participate in ALL study procedures
5. English speaking
6. Ambulatory
7. Must be able to identify a study partner who is well acquainted with the participant for at least 2 years, to answer questions either in person or over the telephone about the participants' activities of daily living, and to corroborate behavioral and cognitive problems and history of brain injury
8. History of combat deployment
9. For blast-related mTBI group: must be active duty or DEERS-eligible, currently or formerly enrolled in the 4 week intensive outpatient program at NICoE, have experienced 1 or more blast-related mTBIs during tours of duty and report experiencing changes in mood, behavioral or cognitive problems (blast-related mTBI considered here and confirmed in EMR as: blast exposure from explosive device resulting in mTBI which fits criteria defined by VA DoD mTBI guidelines which include at least one of: at time of injury - LOC 0-30 minutes, AOC up to 24hrs, PTA 0-1 day, GCS 13-15)
10. DEERS-eligible for all participants
11. For control group 1: history of mTBI with no blast-related mTBIs (as confirmed in EMR and/or by the BISQ and QCube) 12. For control group 2: No lifetime history of TBI (as confirmed by the BISQ and/or EMR)

Exclusion Criteria:

1. Had a moderate or severe brain injury that required hospitalization
2. Significant systemic illness or unstable medical conditions including: uncontrolled diabetes mellitus, uncorrected hypothyroidism or hyperthyroidism, or systemic cancer
3. Diagnosis of schizophrenia, psychosis, or other psychological disorder (Note: blast-related mTBI group will not be excluded if they have a stable diagnosis of post-traumatic stress disorder, depression and anxiety resulting from their military experience; disorders existing prior to military service will serve as an exclusion)
4. Current and active alcohol or substance abuse or dependence (DSM V criteria) within the past 6 months
5. Clinically significant laboratory test abnormalities (such as hematology, chemistry, urinalysis, ECG) or significant impairment of liver or renal function
6. Significant cerebrovascular disease (such as TIA, stroke) or cardiovascular disease (such as uncontrolled hypertension, atrial fibrillation)
7. Impairment of visual or auditory acuity sufficient to interfere with completion of study procedures
8. Education level < 10 years
9. The presence of any MRI-incompatible prostheses or ferromagnetic metal, or any other condition that would preclude ability to undergo MRI or PET (such as claustrophobia or obesity, >350 lbs and/or unable to fit in scanners)
10. History of risk factors for torsade de pointes or take drugs known to prolong the QT interval
11. Had 2 or more PET scans in the last year, or other significant exposure to radiation (i.e. radiation therapy)
12. Diagnosis of neurodegenerative or neurological diseases and dementia (other than CTE) such as Alzheimer's disease, Parkinson's disease, vascular dementia, Huntington's disease, Pick's disease, Lewy Body Dementia, frontotemporal dementia, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, or multiple sclerosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blast-related mTBI group; Assessments will include:(i) neuropsychological and neurobehavioral testing, (ii) MRI, with a special emphasis on (iii) PET, using emerging tracers for tauopathy ([18F]PI-2620), and amyloid ([18F]florbetaben).	Drug: [18F]PI-2620; The participant will be injected with 5 mCi (185 MBq) [18F]PI-2620 via a short line which will be placed in an intravenous line in an antecubital vein. Subjects will be placed in the scanner after injection and dynamic scans will be acquired for 0 to 60 minutes post injection.
Experimental: mTBI not blast-related (control group 1); Assessments will include:(i) neuropsychological and neurobehavioral testing, (ii) MRI, with a special emphasis on (iii) PET, using emerging tracers for tauopathy ([18F]PI-2620), and amyloid ([18F]florbetaben).	Drug: [18F]PI-2620; The participant will be injected with 5 mCi (185 MBq) [18F]PI-2620 via a short line which will be placed in an intravenous line in an antecubital vein. Subjects will be placed in the scanner after injection and dynamic scans will be acquired for 0 to 60 minutes post injection.
Experimental: no history of TBI (control group 2); Assessments will include:(i) neuropsychological and neurobehavioral testing, (ii) MRI, with a special emphasis on (iii) PET, using emerging tracers for tauopathy ([18F]PI-2620), and amyloid ([18F]florbetaben).	Drug: [18F]PI-2620; The participant will be injected with 5 mCi (185 MBq) [18F]PI-2620 via a short line which will be placed in an intravenous line in an antecubital vein. Subjects will be placed in the scanner after injection and dynamic scans will be acquired for 0 to 60 minutes post injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tau deposition in the brain as measured with PI-2620 PET	Tau deposition in the brain of military personnel with blast-related mTBI, non-blast mTBI or no history of TBI will be measured with PI-2620 using positron emission tomography.	1 day
Amyloid deposition in the brain as measured with Florbetaben PET	Amyloid deposition in the brain of military personnel with blast-related mTBI, non-blast mTBI or no history of TBI will be measured with Florbetaben using positron emission tomography.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of brain MR imaging with PI-2620 brain PET imaging	Brain MR imaging will be performed and results correlated with PI-2620 brain PET imaging	1 day
Neurocognitive deficits present in military personnel with blast-related mTBI as measured with NICoE	Neuropsychology assessment will be performed with NICoE, an intensive outpatient program. All subjects will undergo a battery of standardized questionnaires and neuropsychological tests that will characterize the cohort across multiple neuropsychological domains.	up to 4 weeks

Collaborators and Investigators

• Sponsor: Life Molecular Imaging SA
• Collaborators: Walter Reed National Military Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2021
• Primary Completion (Actual): May 12, 2022
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: February 9, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Actual): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: TBI; Traumatic Brain Injury; Tau PET; [18F]PI-2620; Florbetaben
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Brain Concussion
• Other Study ID Numbers: 18-03690

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No