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

NCT05337774 | Terminated Phase 1 FDA Drug

• 1 other identifier: 18-03690
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Traumatic Brain Injury

Keywords

Tau PET; [18F]PI-2620; Florbetaben; TBI; Traumatic Brain Injury

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Correlation of brain MR imaging with PI-2620 brain PET imaging

  1 day

• Neurocognitive deficits present in military personnel with blast-related mTBI as measured with NICoE

  up to 4 weeks

Study Arms (3)

Blast-related mTBI group

EXPERIMENTAL

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

mTBI not blast-related (control group 1)

EXPERIMENTAL

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

no history of TBI (control group 2)

EXPERIMENTAL

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

Interventions

[18F]PI-2620 DRUG

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.

Blast-related mTBI group; mTBI not blast-related (control group 1); no history of TBI (control group 2)

Eligibility Criteria

• Age: 25 Years - 54 Years
• Gender Eligibility Details: Due to limited participant availability women will not be included in the study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male
• Right-handed
• Age 25-54
• Agree to participate in ALL study procedures
• English speaking
• Ambulatory
• 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
• History of combat deployment
• 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)
• DEERS-eligible for all participants
• 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)

You may not qualify if:

• Had a moderate or severe brain injury that required hospitalization
• Significant systemic illness or unstable medical conditions including: uncontrolled diabetes mellitus, uncorrected hypothyroidism or hyperthyroidism, or systemic cancer
• Current and active alcohol or substance abuse or dependence (DSM V criteria) within the past 6 months
• Clinically significant laboratory test abnormalities (such as hematology, chemistry, urinalysis, ECG) or significant impairment of liver or renal function
• Significant cerebrovascular disease (such as TIA, stroke) or cardiovascular disease (such as uncontrolled hypertension, atrial fibrillation)
• Impairment of visual or auditory acuity sufficient to interfere with completion of study procedures
• Education level \< 10 years
• 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)
• History of risk factors for torsade de pointes or take drugs known to prolong the QT interval
• Had 2 or more PET scans in the last year, or other significant exposure to radiation (i.e. radiation therapy)
• 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

Sponsors & Collaborators

• Life Molecular Imaging SA: lead
• Walter Reed National Military Medical Center: collaborator

Study Sites (1)

Walter Reed National Military Medical Center (WRNMMC)

Bethesda, Maryland, 20889, United States

Location

MeSH Terms

Conditions

Brain Concussion; Brain Injuries, Traumatic

Interventions

((18)F)PI-2620

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an exploratory Phase 1, case-control study. Neuroimaging, neuropsychological tests, medical history reviews, and questionnaires will be collected for all eligible subjects.

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: April 20, 2022
• Study Start: June 7, 2021
• Primary Completion: April 30, 2022
• Study Completion: April 30, 2022
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)