Repetitive Head Impacts
Conditions
Keywords
Brain injury, Glutathione, MR spectroscopy, Non- invasive, GGC, RHI, TES, Brain, Blood
Brief summary
The goal of this clinical trial is to test whether the gamma - glutamylcystiene (GGC) oral supplement can reach the brain and subsequently increase antioxidant glutathione (GSH) level in people with repetitive head impact (RHI). This will reduce the oxidative stress related injury in people with RHI.This unique study's main objective is to test the: 1. Change in GSH in brain and blood levels through GGC supplementation. 2. Change in the cognitive function in RHI patients due to GGC supplementation.
Detailed description
This study is designed to evaluate the effects of GGC supplementation in patients with a history of repetitive head impacts (RHI) who are at risk for developing Traumatic Encephalopathy Syndrome (TES). The trial will include specific individuals who satisfy the eligibility criteria.
Interventions
DRUGGamma-glutamylcysteine (GGC)
400mg tablet orally (two times) per day.
Sponsors
Pravat Mandal
Chuck Noll Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Retired NFL player, retired Navy SEAL/army personnel with combat experience exposed to repetitive head impact; * Memory and behavioral complaint per self- or informant-report; * Age (30 to 70 years of age) years; * Able to read and write in English and to give consent to participate in the study.
Exclusion criteria
* Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments in the eyes, skin, or body. * Subjects with claustrophobia. * Subject with mild cognitive impairment \[TICS score of 29 or lower OR \>=1.0 standard deviations below age-expectation on at least two cognitive members within the same cognitive domain (e.g. memory, attention, etc.) on the baseline neuropsychological testing; * Subjects with a history of cancer; * Subjects with active psychosis or delirium; * Subjects with chronic kidney (creatinine \> 1.5mg/dL) or liver disease (AST ≥ 1.5 ULN; ALT ≥1.5 ULN) within 30 days prior to enrollment; * Subjects on antioxidant therapy (gingko biloba or N-acetylcysteine) or illicit drug abuse/dependence (cocaine, heroin, marijuana, or fentanyl; * Repeated head injury patients with neurosurgical intervention and; * Subjects with repeated head injury within the last 90 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in brain glutathione levels (mM) in people with Repetitive Head Injury (RHI) using Magnetic Resonance Spectroscopy in pre and post supplementation. | 12 months | (MRS) is a non-invasive imaging technique, to detect various neurochemical (e.g. glutathione) using MEGA-PRESS sequence from 1H MR spectroscopy. |
| Changes in baseline blood glutathione levels (µmol/l) in people with RHI due to GGC supplementation. | 12 months | — |
| Changes in blood iron levels(ng/μl) in people with RHI due to GGC supplementation. | 12 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between glutathione and iron levels in the brain and blood with dysbiotic features of the gut microbiome in people with RHI. | 12 months | Brain imaging, blood and stool samples will be collected to determine the correlation between glutathione and iron levels in the brain and blood with dysbiotic features of the gut microbiome in people with RHI. |
| Changes from baseline in the cognitive functions (immediate memory, visuospatial memory, language etc) using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in people with RHI . | 12 months | Interpretation: Higher scores \> 70 indicate greater cognitive function (PMID =36648917) |
| Changes in brain iron levels (ppb) in people with RHI using susceptibility mapping between pre and post supplementation. | 12 months | — |
| Changes from baseline in the cognitive functions ( executive functions like attention, speed, and mental flexibility ) using Trail Making Test (TMT) A&B in people with RHI. | 12 months | Scoring Method: The average scores are as follows: * Trail A - 29 seconds * Trail B - 75 seconds Interpretation: Higher scores indicate greater impairment |
| Changes from baseline in the cognitive functions and emotional well-being using Delis-Kaplan Executive Functioning System (D-KEFS) Color Word Interference test in people with a RHI | 12 months | Interpretation: Higher score (\> 7) (PMID=21122190) indicates greater executive functions which includes cognitive abilities essential for tasks such as planning, problem-solving, and decision-making. |
| Changes from baseline in the cognitive functions and emotional well-being using Test of Premorbid Functioning (TOPF ) in people with RHI (PMID=36648917) | 12 months | Interpretation of the results: Higher scores (\>45 above 315191110 indicate better cognitive and memory function. |
| Changes from baseline in the cognitive functions and emotional wellbeing using Brief Symptom Inventory (BSI-18) (self-report) in people RHI . | 12 months | Scoring Method: Each item is scored on a 0-4 scale, with the total score indicating the severity of distress. Interpretation: Higher total scores indicate greater severity of psychological distress. |
| Changes from baseline in the cognitive functions and emotional well-being using PROMIS Cognitive Function -Short Form 8a (self-report) tool in people RHI. | 12 months | Scoring Method: Raw Score: 8-40 Interpretation: Lower scores on this measure indicate greater subjective cognitive difficulty. |
Countries
United States
Contacts
CONTACTPravat K MANDAL, PHD
PRINCIPAL_INVESTIGATORPravat K Mandal, PhD
University of Pittsburgh
Outcome results
None listed