Gamma‑glutamylcysteine to raise brain glutathione in people with repetitive head impacts

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

This trial will test whether an oral supplement called GGC can get into the brain and raise antioxidant glutathione levels in people with a history of repetitive head impacts, such as retired NFL players or combat veterans.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 30 Years to 70 Years
• Sex: All
• Sponsor: University of Pittsburgh (Academic / other)
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT07050173 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional trial gives oral gamma‑glutamylcysteine (GGC) to adults with prior repetitive head impacts and measures changes in glutathione (GSH) in the brain and blood using MR spectroscopy and blood tests. Cognitive and behavioral testing is performed at baseline and after supplementation to look for related changes. Eligibility focuses on people aged 30–70 with self- or informant-reported memory or behavior complaints and without MRI contraindications or major medical illnesses. The primary goal is to confirm CNS penetration and biochemical effect of GGC; clinical effects on cognition are secondary and exploratory.

Who should consider this trial

Good fit: Ideal candidates are adults aged 30–70 with a history of repetitive head impacts (for example retired NFL players or combat veterans) who have self- or informant-reported memory or behavioral complaints and can undergo MRI and study visits.

Not a fit: People with significant cognitive impairment on screening, active psychosis or delirium, a history of cancer, advanced liver or kidney disease, or MRI contraindications are unlikely to benefit from or be eligible for this protocol.

Why it matters

Potential benefit: If successful, GGC could raise brain antioxidant levels, reduce oxidative stress, and potentially slow or improve cognitive and behavioral symptoms related to repetitive head impacts.

How similar studies have performed: Preclinical work and limited human data suggest boosting glutathione can reduce oxidative stress, but using oral GGC to raise brain GSH in people with repetitive head impacts is relatively novel and not yet well established.

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.

Where this trial is running

Pittsburgh, Pennsylvania

• UPMC Presbyterian Hospital — Pittsburgh, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Pravat K Mandal, PhD — University of Pittsburgh
• Study coordinator: Pravat K MANDAL, PHD

Conditions Repetitive Head Impacts; Brain injury; Glutathione; MR spectroscopy; Non- invasive; GGC; RHI; TES