An Investigation of the Biological and Neuronal Mechanisms of Post Traumatic Stress Disorder, Depression and Post-Concussive Syndrome Onset Following a Traumatic Brain Injury

NCT02019654 | Completed

• 2 other identifiers: 14003214-NR-0032
• Study Type: observational
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Background: A traumatic brain injury (TBI) could mean a person is at high risk for other long-lasting problems. These problems could include post-traumatic stress disorder (PTSD), depression, and post-concussive syndrome (PCS). For example, about 700,000 Americans each year who have a TBI later go on to have PTSD also. Depression and PCS are also common in people who had a TBI. Some people will have these problems later. These problems can seriously interfere with a person s life. Some people will not have these problems at all. There are many reasons for this difference. Researchers think the main reason is that people have different genetic and environmental influences. Right now, we only have few kinds of treatments to prevent or treat these problems after a TBI. The few treatments we have often do not work well. It is important to understand what factors make a person at high risk for these problems after a TBI. This could allow researchers and doctors to help address these problems early. Addressing these problems earlier may help a person have better health in the long run. Objectives:

• To study the biological changes that happen after mild to moderate TBI which could be linked to the onset of PTSD, depression, and post-concussive syndrome
• To study brain mechanisms that could explain risks for getting a psychiatric disorder after mild to moderate TBI. This will be done using a test called functional MRI (fMRI). This test takes images of the brain while a person is doing a simple task. Eligibility:
• Men and women who are 18 to 65 years old.
• Had a mild to moderate TBI (including concussion) in the last month. Design:
• 5 outpatient visits to the NIH Clinical Center over one year.
• The first visit is a screening visit to see if you can join the study. This visit must happen within 30 days of the TBI. The visit includes lab work (blood and urine), a history and physical exam done by a physician or nurse practitioner, and a psychiatric interview with a behavioral health nurse.
• Visits 2, 3, 4 and 5 happen at one, three, six and twelve months post-injury. At these visits participants may have some or all of the following tests: blood and saliva collection, urine collection, questionnaires and interviews to assess symptoms, a test to see your response to stress (called hydrocortisone challenge), and fMRI brain imaging.
• This study does not provide treatment.
• This study is not a substitute for seeing a primary care provider.
• This study should not replace any therapies you may be taking.

Conditions

Traumatic Brain Injury; PTSD; Depression

Keywords

Post-Traumatic Stress Disorder (PTSD); Traumatic Brain Injury; Neuroendocrine; Epigenetics; Natural History

Outcome Measures

Primary Outcomes (1)

• Examine proteomic concentrations of inflammatory proteins and neuropeptides following TBI and determine if these biomarkers relate to a greater risk for PTSD, depression or PCS.

  Protein concentrations of inflammatory proteins (IL-1, IL-6, CRP), and lower concentrations of neuropeptides (IGF-1, BDNF, galanin, NPY) and higher concentrations of (SB100, GFAP) collected at the first appointment will predict the onset of PTSD, depression or PCS.

  Visit 1 (Month 1) and Visit 3 (Month 3)

Secondary Outcomes (5)

• We will investigate the activation pattern and effective connectivity between the amygdala and other target regions regulating emotions (e.g., vmPFC or ACC) by analyzing fMRI data in patients following a TBI. We propose that the neurocircuitry-b...

  Visits: 2, 3

• Participants who develop PTSD, depression, or PCS will exhibit differential neuroendocrine functioning test responses using hydrocortisone stimulation test compared to controls who are resistant to these disorders.

  Visits: 2,3,4,5

• Examine reported sleep quality following the TBI and determine if sleep disturbance is associated with the onset of PTSD, PCS or depression

  Visits: 2,3,4,5

• Examine epigenetic modifications (i.e. DNA methylation) and genetic predisposition that may relate to the risk of developing PTSD, depression or PCS onset following a TBI.

  Visits: 2,3,4,5

• Compare the use of resilience traits/abilities in participants who develop PTSD, depression or PCS to TBI participants who are resistant to these disorders.

  Visits: 2,3,4,5

Study Arms (1)

1

Mild or moderate TBI within the past 30 days

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will follow patients who sustained a mild or moderate TBI. Up to 120 participants (target n of completers = 100) will be enrolled into the study within 30 days of the TBI and will be followed over one year. Two groups will emerge: (1) those who develop PTSD, PCS, or depression and (2) those who are resistant to developing these disorders. Participants must be enrolled in CNRM recruiting protocol (11-N-0084), evaluated for a TBI at the George Washington University Hospital, or referred from the NIH/CC Office of Patient Recruitment. NIH employees may participate.

You may qualify if:

• Participants must be enrolled in CNRM recruiting protocol (11-N-0084) or evaluated for a TBI at theGeorge Washington University Hospital, or referred from the NIH/CC Office of Patient Recruitment.
• Participants may be NIH employees/staff, except for those who are employed by NINR or subordinates, relatives, and/or co-workers of NINR employees/staff or study investigators.
• Participants will have had a mild to moderate TBI (GCS between 9 and 15) in the previous 30 days.
• Participants will be between the age of 18 and 65 years
• Ability to give own consent
• Demonstrate understanding of the protocol by passing a short consent quiz with a score of 6.

You may not qualify if:

• Psychiatric Risks: Actively suicidal or at risk for suicide
• Previous or current diagnosis of schizophrenia, bipolar disorder, other psychoses.
• Current diagnosis of depression.
• Previous or current PTSD.
• Current diagnosis of PCS.
• Current alcohol or drug abuse or dependence.
• Pregnancy.
• Under treatment for major illness or injury that may put the participant at higher risk during participation (such as: IV therapy for severe infections, chemotherapy for cancer, multiple necessary surgical interventions for injuries, unstable cardiac disease, severe immune dysfunction, etc.).
• History of any endocrine disorder or dysfunction, unless cleared via an endocrinology consult (including thyroid, adrenal and pituitary disorders).
• Abnormal lab values that may indicate endocrine disorder or dysfunction (unless cleared by endocrine consult) or that may suggest major illness as described above as determined by the screening clinician.
• Unstable diabetes.
• Participant may be able to participate in the study but will not be able to have an MRI if they have any of the following:
• Metal in the body such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants or shrapnel fragments, or if they are a welder or metal worker.
• Claustrophobia
• Are not able to lie comfortably flat on their back for up to 90 minutes.

Sponsors & Collaborators

• National Institute of Nursing Research (NINR): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Brain Injuries, Traumatic; Stress Disorders, Post-Traumatic; Depression

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Kevin A Camphausen, M.D.

  National Institute of Nursing Research (NINR)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2013
• First Posted: December 24, 2013
• Study Start: February 3, 2015
• Primary Completion: July 27, 2020
• Study Completion: July 27, 2020
• Last Updated: September 6, 2022

Record last verified: 2022-09

Locations

US (1)