PET-MRI in Chronic Traumatic Brain Injury (CTBI)

NCT03241732 | Enrolling By Invitation

• 1 other identifier: 17D.138
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Chronic Traumatic Brain Injury

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)

Outcome Measures

Primary Outcomes (2)

• Fluorodeoxyglucose positron emission tomography (FDG-PET).

  To measure inflammation and oxidative damage in the brain.

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

• Functional magnetic resonance imaging (fMRI).

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

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

Secondary Outcomes (14)

• Heart rate variability

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

• Galvanic Skin Temperature

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

• Subjective Units of Distress

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

• Blood plasma and serum analysis

  Screening at Baseline, and if enrolled 90 ± 30 days

• Blood plasma and serum analysis

  Follow up, post NET enrolled 90 ± 30 days

Study Arms (4)

Dietary (AID) Cohort

ACTIVE COMPARATOR

Anti-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.

Other: Anti-inflammatory Diet

Intravenous/Oral NAC Cohort

ACTIVE COMPARATOR

N-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.

Dietary Supplement: N-acetyl Cysteine

Control Cohort

NO INTERVENTION

Control 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 COMPARATOR

Eligible 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.

Behavioral: Neuro Emotive Technique

Interventions

Anti-inflammatory Diet OTHER

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

Dietary (AID) Cohort

N-acetyl Cysteine DIETARY_SUPPLEMENT

Intravenous and Oral n-acetyl cysteine

Intravenous/Oral NAC Cohort

Neuro Emotive Technique BEHAVIORAL

Neuro Emotive Technique sessions

Neuro Emotive Technique (NET)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.
• 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

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (2)

Thomas Jefferson University, Marcus Institute of Integrative Health Centers

Philadelphia, Pennsylvania, 19107, United States

Location

Thomas Jefferson University, Marcus Institute of Integrative Health Centers

Villanova, Pennsylvania, 19085, United States

Location

Related Publications (3)

• 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.

  PMID: 37694125 RESULT

• 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.

  PMID: 36699521 DERIVED

• 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.

  PMID: 33660691 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; Brain Concussion

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Andrew B. Newberg, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an Open Label study.
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: August 7, 2017
• Study Start: June 7, 2017
• Primary Completion (Estimated): July 8, 2027
• Study Completion (Estimated): July 8, 2027
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)