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Chronic Traumatic Brain InjuryPET-MRIcTBINCT03241732

PET-MRI in Chronic Traumatic Brain Injury (CTBI)

A study testing Anti-inflammatory Diet, N-acetyl Cysteine and Neuro Emotive Technique in people with Chronic Traumatic Brain Injury, run by Thomas Jefferson University at 2 sites in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
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Trial summary

Chronic Traumatic Brain Injury (cTBI) symptoms exist in individuals who experienced previous traumatic brain injuries. There are 80-90 thousand individuals who are clinically diagnosed with cTBI, with estimated costs at greater than 60 billion dollars. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Chronic Traumatic Brain Injury
What is being tested?
Anti-inflammatory Diet, N-acetyl Cysteine and Neuro Emotive Technique
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
2 sitesUnited States
Study dates
7 Jun 2017to 8 Jul 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Individuals with a history of TBI and complaints of persistent symptoms including cognitive impairment, emotional disturbances, headache, or other symptoms associated with TBI
  • Age 18-80 years old
  • Patients had no other pre-existing history (i.e. prior to the TBI) of significant medical, neurological, or psychological disorders such as schizophrenia or active substance abuse.
  • Minor, stable health problems that should have no substantial effect on cerebral blood flow will be allowed (i.e. controlled hypertension, medication controlled diabetes)
  • Able to give informed consent and willing to complete the study
  • Patients will be allowed to be taking medications or supplements at the initial intake, but they must be on a stable dose regimen for at least 1 month
  • Women of childbearing potential will confirm a negative pregnancy test NET Substudy: Anxiety and/or distress associated with TBI or TBI symptoms by measurement with Subjective Units of Distress, and biofeedback screening

Who cannot join

  • Previous brain surgery.
  • Cognitive impairment with significant impact on activities of daily living and/or a score on the Mini-Mental Status examination (or similar) of 25 or lower
  • Intracranial abnormalities that may complicate interpretation of the brain scans (e.g., stroke, tumor, vascular abnormality affecting the target area).
  • Pregnant or lactating women.
  • Enrollment in active clinical trial/ experimental therapy within the prior 30 days.
  • Any pre-existing medical conditions that may interfere with cerebral function.
Show all 11Show fewer
  • Subject is unable or unwilling to lie still in the scanner (i.e. due to claustrophobia or weight > 350 pounds)
  • Subject has metal in their body or other reason that they cannot undergo magnetic resonance imaging.
  • Additional exclusionary criteria for the NAC arm:
  • Patients taking medications that might interact with the NAC involved in this study will be evaluated on a case by case basis by the PI or study physician.
  • Patients that have a history of uncontrolled conditions, e.g.: diabetes, asthma, gastroesophageal reflex disease, or thyroid conditions

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States2 sites
  • Thomas Jefferson University, Marcus Institute of Integrative Health Centers

    Philadelphia, Pennsylvania, 19107

  • Thomas Jefferson University, Marcus Institute of Integrative Health Centers

    Villanova, Pennsylvania, 19085

Other trials in United States

About this study

Official title: Defining Neurobiological Signatures for Chronic Traumatic Brain Injury Using PET-MRI Technology

Chronic Traumatic Brain Injury (cTBI) symptoms exist in individuals who experienced previous traumatic brain injuries. There are 80-90 thousand individuals who are clinically diagnosed with cTBI, with estimated costs at greater than 60 billion dollars. However, there is a lack of studies using comprehensive diagnostic imaging tools to better understand physiological ramifications of the injury that may help guide therapy. This study uses integrative medicine approaches for persons with cTBI. Another aim of this study will be a continuation of this protocol in an effort to address the ongoing distressing physiological and psychological (anxiety and depression) symptoms associated with cTBI. After completion of the initial 3 study arms, the investigators have amended the protocol to evaluate the physiological and psychological effects and potential symptom improvement of integrative medicine approaches in cTBI patients using the Neuro Emotive Technique (NET). Participants may be re-enrolled in the NET group after completion of participation in the initial study arms. The participants in the NET substudy will be interviewed about Subjective Units of Distress (SUDS) associated with the cTBI event initially and after completion of the NET sessions.

Read the detailed description

The purpose of this project was to create a comprehensive, extensive, longitudinal diagnostic evaluation of cTBI patients. The evaluation uses a battery of neurocognitive tests, laboratory levels of specific inflammatory compounds, and Positron Emission Tomography (PET) using Fluoro deoxyglucose (FDG) and functional Magnetic Resonance Imaging (fMRI) at baseline and follow up. Participants were evaluated initially with PET, and then at approximately 3 and 6 months to determine the time course of changes within the brain associated with the integrative medicine approach. Three groups of participants were enrolled in the study: a control group, an anti-inflammatory diet group, and an N-acetyl cysteine (NAC) group; NAC is the N-acetyl derivative of the naturally occurring amino acid, L-cysteine. NAC is a common over-the-counter supplement that is also available as an injectable pharmaceutical that protects the liver in cases of acetaminophen overdose. Laboratory studies have displayed some benefits in use of NAC to reduce markers of oxidative damage, protect against cell death, and to increase glutathione in blood, which might be useful in preventing oxidative damage in cTBI patients.

Amendment:

The investigators have amended the original protocol to add a new arm. The purpose of this sub-study is to 30 enroll subjects who have physiological and/or psychological (depression and/or anxiety) symptoms associated with cTBI. Enrollment in this arm of the study would allow for re-enrollment of participants from who still have persistent anxiety, depression symptoms or distress associated with TBI after completing the first phase of this protocol (referenced above). Participants would be evaluated (or re-evaluated) with a battery of neurocognitive tests, including SUDS, NET, and biofeedback measures anxiety levels and receive baseline PET-MRI imaging and follow up functional MRI, neurocognitive tests, including SUDS, NET, and biofeedback measures.

In addition to assessing symptoms associated with TBI, subjects will receive five sessions of Neuro-emotive Technique to address ongoing mood and anxiety symptoms and is conducted by a trained practitioner with clinical credentials in mental health. Subjects who have participated in the initial study will be re-consented if enrolled in the Neuro Emotive Technique Substudy. The investigators will also enroll new subjects with TBI to be enrolled in the NET substudy cohort. In order to gain a greater understanding of the NET program to evaluate whether it reduces anxiety and affects the physiology of the brain in persons with TBI, we believe the potential benefits outweigh the risks. A prescreening interview will be conducted that inquires about current and past treatment for the TBI. In addition, a brief Subjective Units of Distress discussion will assist to determine the extent to which the subject is experiencing distress from TBI or its effects. Upon (re) enrollment and after the completion of the NET sessions. To assess the level of distress, subjects will receive a pre and post biofeedback testing evaluation that measures heart rate variability (HRV) and galvanic skin resistance (GSR) in conjunction with recollection of distress. Pre and post NET blood draw and blood plasma and serum analysis will provide addition information to measure inflammation and immune function for participants in the NET substudy.

Being tested
Anti-inflammatory Diet, N-acetyl Cysteine, Neuro Emotive Technique
Keywords
Traumatic Brain Injury, TBI, Brain Trauma, N-acetyl cysteine, Concussion, NAC, Integrative Medicine, Functional magnetic resonance imaging or functional MRI, fMRI, PET, Positron emission tomography, MRI, magnetic resonance imaging, Chronic Traumatic Brain Injury, Neuro Emotive Technique, Subjective Units of Distress (SUDS)
Medical subject headings
Brain Injuries, Traumatic, Brain Concussion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-inflammatory DietOther

    Integrative diet that reduces saturated fats and carbohydrates and emphasizes proteins and omega-3 fats that help reduce inflammation and oxidative damage.

  • N-acetyl CysteineDietary supplement

    Intravenous and Oral n-acetyl cysteine

  • Neuro Emotive TechniqueBehavioural

    Neuro Emotive Technique sessions

Study groups in NCT03241732
Study groupRoleWhat they receive
Dietary (AID) CohortActive comparatorAnti-inflammatory Diet: This arm will focus on adjusting dietary practices to eat foods that have lower amounts of inflammatory foods that might help reduce overall inflammation in the brain and body. This arm will introduce patients to an integrative diet that reduces saturated fats and carbohydrates and emphasizes proteins and omega-3 fats that help reduce inflammation and oxidative damage.
Receives: Other: Anti-inflammatory Diet
Intravenous/Oral NAC CohortActive comparatorN-acetyl Cysteine: This arm provide patients with a natural supplement, n-acetyl cysteine (NAC) which is the N-acetyl derivative of the naturally occurring amino acid, L-cysteine, that supports antioxidants to reduce oxidative damage in the body. NAC is a common over-the-counter supplement.Laboratory studies have suggested that NAC might have a beneficial effect in neurodegenerative disorders such as TBI. Patients in this arm will receive IV NAC once a week plus oral NAC supplement 500 mg twice per day for approximately 3 months until the follow up evaluation.
Receives: Dietary Supplement: N-acetyl Cysteine
Control CohortNo interventionControl Group: Standard of Care Treatment for at least 3 months. After the first 3 month, participants in this arm may crossover to the NAC study arm.
Neuro Emotive Technique (NET)Active comparatorEligible participants would be evaluated (or re-evaluated) receive neurocognitive tests, and receive baseline PET-MRI and follow up MRI imaging; pre-screening measures distress by the Subjective Units of Distress interview, biofeedback measures of heart rate variability (HRV) and galvanic skin resistance (GSR) and Baseline and post NET blood plasma and serum analysis to measure inflammation and immune function. Participants from the initial study will be re-consented if enrolled in the Neuro Emotive Technique Substudy. SUDS, biofeedback and surveys, MRI imaging and blood draws will be completed again after the 5 NET sessions are complete.
Receives: Behavioral: Neuro Emotive Technique

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fluorodeoxyglucose positron emission tomography (FDG-PET).

    To measure inflammation and oxidative damage in the brain.

    Measured: Baseline in the primary study for waitlist and control groups, not in the NET substudy.

  2. Functional magnetic resonance imaging (fMRI).

    This scan will be used to assess functional connectivity, tractography, and brain volume.

    Measured: NET Substudy: Baseline, 90 ± 30 days and 180 ± 30 days.

Secondary outcomes (14)
  1. Heart rate variability

    NET Substudy: This assessment is a Biofeedback evaluation to measure the physiologic level of distress experienced.

    Measured: Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days

  2. Galvanic Skin Temperature

    NET Substudy: This assessment is a Biofeedback evaluation to measure the physiologic level of distress experienced.

    Measured: Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days

  3. Subjective Units of Distress

    NET Substudy: This assessment is a Likert scale that identifies the level of psychological distress experienced.

    Measured: Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days

  4. Blood plasma and serum analysis

    NET Substudy: Blood draw to evaluate cytokine profile analysis to measure inflammation.

    Measured: Screening at Baseline, and if enrolled 90 ± 30 days

  5. Blood plasma and serum analysis

    NET Substudy: Blood draw to evaluate T Cell profile analysis will measure immune function.

    Measured: Follow up, post NET enrolled 90 ± 30 days

  6. Rivermead Post-Concussion Symptoms Questionnaire.

    This assessment questionnaire will be used as one of the quality of life measures for the study.

    Measured: Baseline, 90 ± 30 days and 180 ± 30 days.

  7. Beck Depression Inventory (BDI).

    This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.

    Measured: Baseline, 90 ± 30 days and 180 ± 30 days.

  8. Speilberger State Trait Anxiety Inventory (STAI).

    This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.

    Measured: Baseline, 90 ± 30 days and 180 ± 30 days.

  9. Profile of Moods Scale (POMS).

    This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.

    Measured: Baseline, 90 ± 30 days and 180 ± 30 days.

  10. Epworth Sleepiness Scale.

    This assessment questionnaire will be used as one of the quality of life measures for the study.

    Measured: Baseline, 90 ± 30 days and 180 ± 30 days.

  11. Mayo-Portland Adaptability Inventory-4.

    This assessment questionnaire will be used as one of the quality of life measures for the study.

    Measured: Baseline, 90 ± 30 days and 180 ± 30 days.

  12. Delis Kaplan Executive Function System (DKEFS) color-word interference.

    This assessment questionnaire may be used as one of the cognitive testings for the study.

    Measured: Baseline, 90 ± 30 days and 180 ± 30 days.

  13. Trails A & B.

    This assessment questionnaire may be used as one of the cognitive testings for the study.

    Measured: Baseline, 90 ± 30 days and 180 ± 30 days.

  14. Forward and reverse digit span.

    This assessment questionnaire may be used as one of the cognitive testings for the study.

    Measured: Baseline, 90 ± 30 days and 180 ± 30 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2017
  2. Study start7 Jun 2017
  3. Primary completion8 Jul 2027 (estimated)
  4. Study completion8 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Crossover
Model description
There were two intervention arms of the study and a control group. Enrollment for these groups was 120 subjects. One arm focused on adjusting dietary practices to eat foods that have a lower amount of inflammatory molecules that might help reduce overall inflammation in the brain and body. The second arm was the N-acetyl cysteine group to provide patients with a natural supplement that support antioxidants in the body. The third arm of the study is a waitlist control group. The fourth arm is a substudy that may re-enroll and re-consent 30 subjects from the original 3 groups, and will recruit additional subjects as needed, who continue to have distress associated with TBI. Subjects will receive sessions with the Neuro Emotive Technique. Participants enrolled in the 4th NET group will be counted in the cohort of 30 for the NET substudy.
Masking
None (open label)
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03241732
Sponsor's protocol ID
17D.138
Acronym
PET-MRIcTBI
Status last verified
Jul 2025
First submitted
11 Jul 2017
Last updated
29 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Muller JJ, Wang R, Milddleton D, Alizadeh M, Kang KC, Hryczyk R, Zabrecky G, Hriso C, Navarreto E, Wintering N, Bazzan AJ, Wu C, Monti DA, Jiao X, Wu Q, Newberg AB, Mohamed FB. Machine learning-based classification of chronic traumatic brain injury using hybrid diffusion imaging. Front Neurosci. 2023 Aug 24;17:1182509. doi: 10.3389/fnins.2023.1182509. eCollection 2023.

    PubMed 37694125
  • Vedaei F, Mashhadi N, Zabrecky G, Monti D, Navarreto E, Hriso C, Wintering N, Newberg AB, Mohamed FB. Identification of chronic mild traumatic brain injury using resting state functional MRI and machine learning techniques. Front Neurosci. 2023 Jan 9;16:1099560. doi: 10.3389/fnins.2022.1099560. eCollection 2022.

    PubMed 36699521
  • Teichner EM, You JC, Hriso C, Wintering NA, Zabrecky GP, Alavi A, Bazzan AJ, Monti DA, Newberg AB. Alterations in cerebral glucose metabolism as measured by 18F-fluorodeoxyglucose-PET in patients with persistent postconcussion syndrome. Nucl Med Commun. 2021 Jul 1;42(7):772-781. doi: 10.1097/MNM.0000000000001397.

    PubMed 33660691

Questions about this trial

What is this clinical trial studying?

A study testing Anti-inflammatory Diet, N-acetyl Cysteine and Neuro Emotive Technique in people with Chronic Traumatic Brain Injury, run by Thomas Jefferson University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fluorodeoxyglucose positron emission tomography (FDG-PET). (time frame: Baseline in the primary study for waitlist and control groups, not in the NET substudy.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03241732, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2025.

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