Monitoring Patients With Repetitive Head Impact With Gamma-glutamylcysteine Supplementation

NCT07050173 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY241200160025
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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. 1.Change in GSH in brain and blood levels through GGC supplementation.
2. 2.Change in the cognitive function in RHI patients due to GGC supplementation.

Conditions

Repetitive Head Impacts

Keywords

Brain injury; Glutathione; MR spectroscopy; Non- invasive; GGC; RHI; TES; Brain; Blood

Outcome Measures

Primary Outcomes (3)

• Changes in brain glutathione levels (mM) in people with Repetitive Head Injury (RHI) using Magnetic Resonance Spectroscopy in pre and post supplementation.

  (MRS) is a non-invasive imaging technique, to detect various neurochemical (e.g. glutathione) using MEGA-PRESS sequence from 1H MR spectroscopy.

  12 months

• 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 Outcomes (8)

• Correlation between glutathione and iron levels in the brain and blood with dysbiotic features of the gut microbiome in people with RHI.

  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 .

  12 months

• 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

• 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

Study Arms (1)

Gamma - Glutamylcystiene

EXPERIMENTAL

Each participant will receive gamma-glutamyl cysteine (GGC) tablet orally 400mg (two times) per day once in the morning and once in the evening for 12 months.

Drug: Gamma-glutamylcysteine (GGC)

Interventions

Gamma-glutamylcysteine (GGC) DRUG

400mg tablet orally (two times) per day.

Also known as: GGC

Gamma - Glutamylcystiene

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pravat Mandal: lead
• Chuck Noll Foundation: collaborator

Study Sites (1)

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Related Publications (2)

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Brain Injuries

Interventions

gamma-glutamylcysteine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Pravat K Mandal, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pravat K MANDAL, PHD

CONTACT

4126999561; mandalpk@pitt.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Research Assistant Professor

Study Record Dates

• First Submitted: June 20, 2025
• First Posted: July 3, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 27, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR

Locations

US (1)