PET-MRI in Chronic Traumatic Brain Injury (CTBI)

Chronic Traumatic Brain Injury Clinical Trial

— PET-MRIcTBI  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03241732
• Other study ID #: 17D.138
• Status: Enrolling by invitation
• Phase: N/A
• Start date: June 7, 2017
• Est. completion date: February 10, 2025

Study information

• Verified date: November 2023
• Source: Thomas Jefferson University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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 biofeedback testing evaluation that measures heart rate variability (HRV) and galvanic skin resistance (GSR) in conjunction with recollection of distress.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 150
• Est. completion date: February 10, 2025
• Est. primary completion date: February 10, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Individuals with a history of TBI and complaints of persistent symptoms including cognitive impairment, emotional disturbances, headache, or other symptoms associated with TBI
• Anxiety and/or distress associated with TBI or TBI symptoms by measurement with Subjective Units of Distress, and biofeedback screening
• 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

Exclusion Criteria:

• 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.

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Chronic Traumatic Brain Injury
• Wounds and Injuries

Intervention

Other:
• Anti-inflammatory Diet
Integrative diet that reduces saturated fats and carbohydrates and emphasizes proteins and omega-3 fats that help reduce inflammation and oxidative damage.

Dietary Supplement:
• N-acetyl Cysteine
Intravenous and Oral n-acetyl cysteine

Behavioral:
• Neuro Emotive Technique
Neuro Emotive Technique sessions

Locations

Country	Name	City	State
United States	Thomas Jefferson University, Marcus Institute of Integrative Health Centers	Philadelphia	Pennsylvania
United States	Thomas Jefferson University, Marcus Institute of Integrative Health Centers	Villanova	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Jefferson University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fluorodeoxyglucose positron emission tomography (FDG-PET).	To measure inflammation and oxidative damage in the brain.	Baseline in all study arms.
Secondary	Heart rate variability	NET Substudy: This assessment is a Biofeedback evaluation to measure the physiologic level of distress experienced.	Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days
Secondary	Galvanic Skin Temperature	NET Substudy: This assessment is a Biofeedback evaluation to measure the physiologic level of distress experienced.	Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days
Secondary	Subjective Units of Distress	NET Substudy: This assessment is a Likert scale that identifies the level of psychological distress experienced.	Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days
Secondary	Functional magnetic resonance imaging (fMRI).	This scan will be used to assess functional connectivity, tractography, and brain volume.	Baseline, 90 ± 30 days and 180 ± 30 days.
Secondary	Rivermead Post-Concussion Symptoms Questionnaire.	This assessment questionnaire will be used as one of the quality of life measures for the study.	Baseline, 90 ± 30 days and 180 ± 30 days.
Secondary	Beck Depression Inventory (BDI).	This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.	Baseline, 90 ± 30 days and 180 ± 30 days.
Secondary	Speilberger State Trait Anxiety Inventory (STAI).	This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.	Baseline, 90 ± 30 days and 180 ± 30 days.
Secondary	Profile of Moods Scale (POMS).	This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.	Baseline, 90 ± 30 days and 180 ± 30 days.
Secondary	Epworth Sleepiness Scale.	This assessment questionnaire will be used as one of the quality of life measures for the study.	Baseline, 90 ± 30 days and 180 ± 30 days.
Secondary	Mayo-Portland Adaptability Inventory-4.	This assessment questionnaire will be used as one of the quality of life measures for the study.	Baseline, 90 ± 30 days and 180 ± 30 days.
Secondary	Delis Kaplan Executive Function System (DKEFS) color-word interference.	This assessment questionnaire may be used as one of the cognitive testings for the study.	Baseline, 90 ± 30 days and 180 ± 30 days.
Secondary	Trails A & B.	This assessment questionnaire may be used as one of the cognitive testings for the study.	Baseline, 90 ± 30 days and 180 ± 30 days.
Secondary	Forward and reverse digit span.	This assessment questionnaire may be used as one of the cognitive testings for the study.	Baseline, 90 ± 30 days and 180 ± 30 days.