- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03241732
PET-MRI in Chronic Traumatic Brain Injury (CTBI) (PET-MRIcTBI)
Defining Neurobiological Signatures for Chronic Traumatic Brain Injury Using PET-MRI Technology
Study Overview
Status
Conditions
Intervention / Treatment
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 biofeedback testing evaluation that measures heart rate variability (HRV) and galvanic skin resistance (GSR) in conjunction with recollection of distress.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19107
- Thomas Jefferson University, Marcus Institute of Integrative Health Centers
-
Villanova, Pennsylvania, United States, 19085
- Thomas Jefferson University, Marcus Institute of Integrative Health Centers
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Dietary (AID) Cohort
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.
|
Integrative diet that reduces saturated fats and carbohydrates and emphasizes proteins and omega-3 fats that help reduce inflammation and oxidative damage.
|
Active Comparator: Intravenous/Oral NAC Cohort
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.
It is used as an injectable pharmaceutical to protect the liver in cases of acetaminophen overdose.
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.
|
Intravenous and Oral n-acetyl cysteine
|
No Intervention: Control Cohort
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.
|
|
Active Comparator: Neuro Emotive Technique
This arm measures effects of NET in individuals with TBI symptoms by evaluating measures of distress, autonomic reactivity, neuroimaging markers, anxiety, health-related, physiological and psychology-related symptoms.
Participants would be evaluated (or re-evaluated) with a battery of neurocognitive tests, and receive baseline PET-MRI and follow up MRI imaging.
Subjects will receive a pre-screening evaluation that measures distress by the Subjective Units of Distress interview, biofeedback measures of heart rate variability (HRV) and galvanic skin resistance (GSR) in conjunction with recollection of distress.
Subjects will receive five sessions of Neuro-emotive Technique.
Subjects who have participated in the initial study will be re-consented if enrolled in the Neuro Emotive Technique Substudy for approximately 2-3 months until the follow up evaluation.
SUDS, biofeedback and surveys will be completed again after the NET sessions are complete.
|
Neuro Emotive Technique sessions
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fluorodeoxyglucose positron emission tomography (FDG-PET).
Time Frame: Baseline in all study arms.
|
To measure inflammation and oxidative damage in the brain.
|
Baseline in all study arms.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Functional magnetic resonance imaging (fMRI).
Time Frame: Baseline, 90 ± 30 days and 180 ± 30 days.
|
This scan will be used to assess functional connectivity, tractography, and brain volume.
|
Baseline, 90 ± 30 days and 180 ± 30 days.
|
Speilberger State Trait Anxiety Inventory (STAI).
Time Frame: Baseline, 90 ± 30 days and 180 ± 30 days.
|
This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.
|
Baseline, 90 ± 30 days and 180 ± 30 days.
|
Profile of Moods Scale (POMS).
Time Frame: Baseline, 90 ± 30 days and 180 ± 30 days.
|
This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.
|
Baseline, 90 ± 30 days and 180 ± 30 days.
|
Beck Depression Inventory (BDI).
Time Frame: Baseline, 90 ± 30 days and 180 ± 30 days.
|
This assessment questionnaire will be used as one of the psychological evaluation questionnaires for the study.
|
Baseline, 90 ± 30 days and 180 ± 30 days.
|
Epworth Sleepiness Scale.
Time Frame: Baseline, 90 ± 30 days and 180 ± 30 days.
|
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.
|
Mayo-Portland Adaptability Inventory-4.
Time Frame: Baseline, 90 ± 30 days and 180 ± 30 days.
|
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.
|
Rivermead Post-Concussion Symptoms Questionnaire.
Time Frame: Baseline, 90 ± 30 days and 180 ± 30 days.
|
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.
|
Heart rate variability
Time Frame: Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days
|
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
|
Galvanic Skin Temperature
Time Frame: Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days
|
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
|
Subjective Units of Distress
Time Frame: Screening at Baseline, and if enrolled 90 ± 30 days and if in waitlist 180 ± 30 days
|
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
|
Delis Kaplan Executive Function System (DKEFS) color-word interference.
Time Frame: Baseline, 90 ± 30 days and 180 ± 30 days.
|
This assessment questionnaire may be used as one of the cognitive testings for the study.
|
Baseline, 90 ± 30 days and 180 ± 30 days.
|
Trails A & B.
Time Frame: Baseline, 90 ± 30 days and 180 ± 30 days.
|
This assessment questionnaire may be used as one of the cognitive testings for the study.
|
Baseline, 90 ± 30 days and 180 ± 30 days.
|
Forward and reverse digit span.
Time Frame: Baseline, 90 ± 30 days and 180 ± 30 days.
|
This assessment questionnaire may be used as one of the cognitive testings for the study.
|
Baseline, 90 ± 30 days and 180 ± 30 days.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Andrew B. Newberg, MD, Thomas Jefferson University
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- MRI
- magnetic resonance imaging
- PET
- Concussion
- fMRI
- TBI
- Traumatic Brain Injury
- Integrative Medicine
- NAC
- N-acetyl cysteine
- Positron emission tomography
- Brain Trauma
- Functional magnetic resonance imaging or functional MRI
- Chronic Traumatic Brain Injury
- Neuro Emotive Technique
- Subjective Units of Distress (SUDS)
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Craniocerebral Trauma
- Trauma, Nervous System
- Brain Injuries
- Wounds and Injuries
- Brain Injuries, Traumatic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Protective Agents
- Respiratory System Agents
- Antioxidants
- Antidotes
- Free Radical Scavengers
- Expectorants
- Anti-Inflammatory Agents
- Acetylcysteine
- N-monoacetylcystine
Other Study ID Numbers
- 17D.138
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Traumatic Brain Injury
-
Brent MaselThe Moody FoundationCompletedChronic Traumatic Brain InjuryUnited States
-
Toronto Rehabilitation InstituteCentre for Aging and Brain Health Innovation; Ontario Neurotrauma FoundationUnknownBrain Injuries, Traumatic | Brain Injury, Chronic | Brain Injury Traumatic Severe | Brain Injury Traumatic ModerateCanada
-
Center for Vision Development, New Market, MarylandUnknownBrain Injuries | Brain Injuries, Traumatic | Traumatic Brain Injury | Brain Injury, Chronic | Injury, Brain, TraumaticUnited States
-
University of ArizonaCompletedTraumatic Brain Injury (TBI) | Chronic Traumatic Encephalopathy (CTE)United States
-
University of California, Los AngelesCompletedTBI (Traumatic Brain Injury) | CTEUnited States
-
Karolinska University HospitalKarolinska InstitutetRecruitingNeurodegenerative Diseases | Traumatic Brain Injury | Chronic Traumatic EncephalopathySweden
-
Virginia Commonwealth UniversityU.S. Department of EducationCompletedTraumatic Brain Injury | Brain Injury, ChronicUnited States
-
Uniformed Services University of the Health SciencesUniversity of California, San FranciscoWithdrawnDementia | Mild Cognitive Impairment (MCI) | Traumatic Brain Injury (TBI) | Post-traumatic Stress Disorder (PTSD) | Chronic Traumatic Encephalopathy (CTE)United States
-
University of Southern CaliforniaEnrolling by invitationTraumatic Brain InjuryUnited States
-
VA Office of Research and DevelopmentVA Boston Healthcare SystemRecruitingMild Cognitive Impairment | Mild Traumatic Brain Injury | Moderate Traumatic Brain InjuryUnited States
Clinical Trials on Anti-inflammatory Diet
-
University of California, San DiegoRecruiting
-
University of California, San DiegoRecruiting
-
Universidade Nova de LisboaHospital Particular do Algarve - HPA SaúdeCompletedRheumatoid ArthritisPortugal
-
National University of Natural MedicineNational Center for Complementary and Integrative Health (NCCIH)CompletedDiabetes Mellitus, Type 2 | PrediabetesUnited States
-
Assiut UniversityNot yet recruitingInflammatory Bowel Diseases
-
Norwegian University of Science and TechnologySt. Olavs HospitalCompletedCardiovascular Diseases | Obesity | Diabetes Mellitus, Type 2Norway
-
Cairo UniversityNot yet recruiting
-
Göteborg UniversitySahlgrenska University Hospital, SwedenCompleted
-
Universidad de CaldasUniversidad Libre; Clinica Comfamiliar RisaraldaCompleted
-
Clinical Hospital Center RijekaUniversity of RijekaCompleted