Monitoring Patients With Repetitive Head Impact With Gamma-glutamylcysteine Supplementation

Official title

Patients With Repetitive Head Impact Orally Supplemented With Gamma-glutamylcysteine: An Open Label Trial With MR Spectroscopy and Neuropsychological Testing

Overview

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

• Drug Gamma-glutamylcysteine (GGC)
  400mg tablet orally (two times) per day.

Primary outcome measures

• Changes in brain glutathione levels (mM) in people with Repetitive Head Injury (RHI) using Magnetic Resonance Spectroscopy in pre and post supplementation. [Time frame: 12 months]
• Changes in baseline blood glutathione levels (µmol/l) in people with RHI due to GGC supplementation. [Time frame: 12 months]
• Changes in blood iron levels(ng/μl) in people with RHI due to GGC supplementation. [Time frame: 12 months]

Secondary outcome measures (8)

• Correlation between glutathione and iron levels in the brain and blood with dysbiotic features of the gut microbiome in people with RHI. [Time frame: 12 months]
• 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 . [Time frame: 12 months]
• Changes in brain iron levels (ppb) in people with RHI using susceptibility mapping between pre and post supplementation. [Time frame: 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. [Time frame: 12 months]
• 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 [Time frame: 12 months]
• Changes from baseline in the cognitive functions and emotional well-being using Test of Premorbid Functioning (TOPF ) in people with RHI (PMID=36648917) [Time frame: 12 months]
• Changes from baseline in the cognitive functions and emotional wellbeing using Brief Symptom Inventory (BSI-18) (self-report) in people RHI . [Time frame: 12 months]
• Changes from baseline in the cognitive functions and emotional well-being using PROMIS Cognitive Function -Short Form 8a (self-report) tool in people RHI. [Time frame: 12 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• UPMC Presbyterian Hospital — Pittsburgh

Publications

• Mandal PK, Dwivedi D, Joon S, Goel A, Ahasan Z, Maroon JC, Singh P, Saxena R, Roy RG. Quantitation of Brain and Blood Glutathione and Iron in Healthy Age Groups Using Biophysical and In Vivo MR Spectroscopy: Potential Clinical Application. ACS Chem Neurosci. 2023 Jun 21;14(12):2375-2384. doi: 10.1021/acschemneuro.3c00168. Epub 2023 May 31. PMID 37257017
• Mandal PK, Saharan S, Tripathi M, Murari G. Brain glutathione levels--a novel biomarker for mild cognitive impairment and Alzheimer's disease. Biol Psychiatry. 2015 Nov 15;78(10):702-10. doi: 10.1016/j.biopsych.2015.04.005. Epub 2015 Apr 14. PMID 26003861

Identifiers

NCT: NCT07050173 · STUDY24120016 · 0025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗