Monitoring Patients With Repetitive Head Impact With Gamma-glutamylcysteine Supplementation

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (8)

• Correlation between glutathione and iron levels in the brain and blood with dysbiotic features of the gut microbiome in people with RHI. [Срок оценки: 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 . [Срок оценки: 12 months]
• Changes in brain iron levels (ppb) in people with RHI using susceptibility mapping between pre and post supplementation. [Срок оценки: 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. [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 12 months]
• Changes from baseline in the cognitive functions and emotional wellbeing using Brief Symptom Inventory (BSI-18) (self-report) in people RHI . [Срок оценки: 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. [Срок оценки: 12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• UPMC Presbyterian Hospital — Pittsburgh

Публикации

• 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

Идентификаторы

NCT: NCT07050173 · STUDY24120016 · 0025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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