Recruiting

Neurodegeneration

Sponsor:

VA Office of Research and Development

Code:

NCT04124029

Conditions

Mild Traumatic Brain Injury

Moderate Traumatic Brain Injury

Mild Cognitive Impairment

Eligibility Criteria

Sex: All

Age: 30 - 70+

Healthy Volunteers: Accepted

Interventions

No Intervention is used for this study but all subjects will be asked to complete electroencephalogram (EEG) testing and an MRI scan.

No intervention is used for this study but all subjects will be asked to complete a venous blood draw procedure and a lumbar puncture procedure.

Study Details

Brief summary:

This is a research study that aims to examine whether Veterans with mild Traumatic Brain Injuries are at risk for dementia by studying their memory, brain wave activity, brain structure and proteins that can be elevated after brain injury and in dementia.

Conditions

Mild Traumatic Brain Injury

Moderate Traumatic Brain Injury

Mild Cognitive Impairment

Study ID

NCT04124029

Start date

Jul 1, 2021

Status verified date

Aug, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 30 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

All Subjects:

  • Intact color vision
  • Visual acuity of 20/30 (or better)
  • Patients must pass effort measures on the TOMM
  • Patients must have intact decision-making capacity
  • Patients must have no contraindications to lumbar puncture including:
  • Being on a blood thinner
  • Aspirin or Plavix
  • Have no space occupying lesion on magnetic resonance imaging (MRI)
  • An International Normalized Ratio (INR) value < 1.4 and platelet count >50,000
  • No epidural infection or overlying cellulitis over the lumbar spine
  • PTSD will be accounted for as a potential confounder and its presence will be included as a covariate in all analyses

Mild traumatic brain injury (TBI) Subjects:

  • Subjects will be recruited who have a physician diagnosis of 1 or more mTBI episodes without concomitant moderate or severe TBI diagnosis
  • Mild TBI: Loss of consciousness greater than 30 minutes, posttraumatic amnesia greater than 24 hours, and/or altered mental status greater than 24 hours

Moderate TBI Subjects:

  • Subjects will be recruited who have a physician diagnosis of 1 or more moderate TBI episodes
  • Moderate TBI: loss of consciousness greater than 30 minutes, posttraumatic amnesia greater than 24 hours, and altered mental status greater than 24 hours

Mild Cognitive Impairment (MCI) Subjects:

  • Subjects will be recruited that meet diagnostic criteria for MCI (without a history of TBI) based on the judgement of a behavioral neurologist following the 2011 MCI criteria
  • Specifically, subjects will test in the impaired range on one or more cognitive domains on neuropsychological testing and will not have impairments in function, i.e. will not meet diagnostic criteria for dementia
  • Subjects with MCI may or may not meet diagnostic criteria for MCI due to AD
  • MCI subjects will be matched for their MoCA score with older TBI subjects

Healthy Controls:

  • Cognitively normal control subjects, age-, education- and sex-matched with mild TBI subjects, but lacking and TBI history
  • All subjects must be within 1 standard deviation of normal on all neuropsychologic testing in order to be enrolled

The investigators will recruit all subjects without regard to gender, race, ethnicity, socioeconomic status, or other factors to allow results of this research to yield the greatest generalizability

Exclusion Criteria:

All Subjects:

  • If the primary language is not English
  • Are unable to understand the informed consent process
  • Have a clinically significant problem with any of the following conditions:
  • A history of traumatic brain injury (TBI) within 1 year of study
  • Suicidal or homicidal ideation requiring intervention
  • Schizophrenia
  • Bipolar disorder
  • Active alcohol or drug abuse
  • Clinically significant neurological disease other than those stated in the inclusion criteria
  • Impaired decision-making ability
  • Patients will be excluded if there are contraindications to MRI including:
  • Implants
  • Shrapnel
  • Aneurysm clips
  • Pacemaker
  • Pregnancy
  • Non-TBI subjects must not have had an TBI
  • No contraindication to lumbar puncture or blood draw including:
  • Being on a blood thinner
  • Aspirin or Plavix
  • No space occupying lesion on MRI that makes lumbar puncture contraindicated

Study Design

Enrollment

800 participants

Anticipated

Interventions and Outcome Measures

Arms

Younger mild Traumatic Brain Injury

mTBI subjects aged 30-59 yo will be recruited who have a physician diagnosis of 1 or more mTBI episodes without concomitant moderate or severe TBI diagnosis (loss of consciousness greater than 30 minutes, posttraumatic amnesia greater than 24 hours, or altered mental status greater than 24 hours). mTBI subjects must pass effort measures on the Test of Memory Malingering (TOMM) and have intact color vision and visual acuity of 20/30 or better in order to be included in the study.

Older mild Traumatic Brain Injury

mTBI subjects aged 60- 90 yo will be recruited who have a physician diagnosis of 1 or more mTBI episodes without concomitant moderate or severe TBI diagnosis (loss of consciousness greater than 30 minutes, posttraumatic amnesia greater than 24 hours, or altered mental status greater than 24 hours). mTBI subjects must pass effort measures on the TOMM and have intact color vision and visual acuity of 20/30 or better in order to be included in the study.

moderate Traumatic Brain Injury

TBI control subjects, age-, education- and sex-matched with mTBI subjects (aged 30-90) will be recruited who have a physician diagnosis of 1 or more moderate TBI episodes (loss of consciousness greater than 30 minutes, posttraumatic amnesia greater than 24 hours, or altered mental status greater than 24 hours). Moderate TBI subjects must pass effort measures on the TOMM and have intact color vision and visual acuity of 20/30 or better in order to be included in the study.

Mild Cognitive Impairment (MCI)

MCI control subjects, age-, education- and sex-matched with older mTBI subjects (aged 60-90) will be recruited if they meet diagnostic criteria for MCI (without a history of TBI) based on the judgement of a behavioral neurologist following the 2011 MCI criteria. Specifically, subjects will test in the impaired range on one or more cognitive domains on neuropsychological testing and will not have impairments in function (i.e. will not meet diagnostic criteria for dementia). MCI subjects will be matched for their Montreal Cognitive Assessment (MoCA) score with older mTBI subjects. Of note, subjects with MCI may or may not meet diagnostic criteria for MCI due to AD. The intent of this control group is to recruit a broad range of MCI subjects without TBI as controls for subjects with cognitive impairment who have a history of mTBI.

Younger Healthy Controls

Cognitively normal control subjects, age-, education- and sex-matched with younger mTBI subjects, but lacking and mTBI history. All subjects must be within 1 standard deviation of normal on all neuropsychologic testing in order to be enrolled.

Older Healthy Controls

Cognitively normal control subjects, age-, education- and sex-matched with older mTBI subjects, but lacking and mTBI history. All subjects must be within 1 standard deviation of normal on all neuropsychologic testing in order to be enrolled.

Interventions

No Intervention is used for this study but all subjects will be asked to complete electroencephalogram (EEG) testing and an MRI scan.

No intervention will be used.

No intervention is used for this study but all subjects will be asked to complete a venous blood draw procedure and a lumbar puncture procedure.

No intervention will be used.

Primary outcome measure

  • To better understand the contribution of mild Traumatic Brain Injury (mTBI) to neurodegeneration with the intent of detecting early behavioral, physiologic, anatomic, and protein evidence of neurodegeneration due to AD and CTE [ Time Frame: 5 years ]

Central Contacts and Locations

Central contacts

Kristina Morreale, BA

(857) 364-2139Kristina.Morreale@va.gov

Locations

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Recruiting

Boston, Massachusetts, United States, 02130-4817

Contacts

Kristina Morreale, BA

(857) 364-2139Kristina.Morreale@va.gov

Principal Investigator:

Katherine Turk, MD

More Information

Sponsor

VA Office of Research and Development

Last update posted

Sep 1, 2026

Last verified

Aug, 2026

Keywords

  • Mild Traumatic Brain Injury
  • Moderate Traumatic Brain Injury
  • Alzheimer's Disease
  • Chronic Traumatic Encephalopathy
  • Neurodegeneration

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-09-01.