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

Primary Purpose

Mild Traumatic Brain Injury

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
[18F]PI-2620
Sponsored by
Life Molecular Imaging SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Mild Traumatic Brain Injury focused on measuring Tau PET, [18F]PI-2620, Florbetaben, TBI, Traumatic Brain Injury

Eligibility Criteria

25 Years - 54 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • Walter Reed National Military Medical Center (WRNMMC)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Blast-related mTBI group

mTBI not blast-related (control group 1)

no history of TBI (control group 2)

Arm Description

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).

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).

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).

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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
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.

Full Information

First Posted
February 9, 2022
Last Updated
December 14, 2022
Sponsor
Life Molecular Imaging SA
Collaborators
Walter Reed National Military Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05337774
Brief Title
Imaging [18F]PI-2620 and [18F]Florbetaben in Military Service Members With Blast Related Mild Traumatic Brain Injury
Official Title
Imaging [18F]PI-2620 and [18F]Florbetaben in Military Service Members With Blast Related Mild Traumatic Brain Injury
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 7, 2021 (Actual)
Primary Completion Date
May 12, 2022 (Actual)
Study Completion Date
May 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Life Molecular Imaging SA
Collaborators
Walter Reed National Military Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Traumatic Brain Injury
Keywords
Tau PET, [18F]PI-2620, Florbetaben, TBI, Traumatic Brain Injury

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
This is an exploratory Phase 1, case-control study. Neuroimaging, neuropsychological tests, medical history reviews, and questionnaires will be collected for all eligible subjects.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Blast-related mTBI group
Arm Type
Experimental
Arm Description
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).
Arm Title
mTBI not blast-related (control group 1)
Arm Type
Experimental
Arm Description
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).
Arm Title
no history of TBI (control group 2)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
[18F]PI-2620
Intervention Description
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.
Primary Outcome Measure Information:
Title
Tau deposition in the brain as measured with PI-2620 PET
Description
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.
Time Frame
1 day
Title
Amyloid deposition in the brain as measured with Florbetaben PET
Description
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.
Time Frame
1 day
Secondary Outcome Measure Information:
Title
Correlation of brain MR imaging with PI-2620 brain PET imaging
Description
Brain MR imaging will be performed and results correlated with PI-2620 brain PET imaging
Time Frame
1 day
Title
Neurocognitive deficits present in military personnel with blast-related mTBI as measured with NICoE
Description
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.
Time Frame
up to 4 weeks

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
Due to limited participant availability women will not be included in the study.
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
54 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: 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 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) 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
Facility Information:
Facility Name
Walter Reed National Military Medical Center (WRNMMC)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20889
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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