NCT07464886

Prefrontal Glutamatergic Modulation by NAC and MBCT for Depression in Youth

Prefrontal Glutamatergic Modulation by N-acetylcysteine and Mindfulness-based Cognitive Therapy for Mild Depression in Youth

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 160 (estimated)
• Sponsor: University of Cincinnati · Academic / Other
• Sex: All
• Age: 15 Years – 24 Years
• Healthy volunteers: Not accepted

Summary

The primary goal is to investigate to what extent changes in glutamate and glutathione modulation and functional integration between brain networks associated with emotion and attention regulation are associated with treatment response in mildly depressed youth.

Detailed description

The specific goals are to determine whether treatment with a combination of mindfulness-based cognitive therapy (MBCT) and N-acetylcysteine (NAC) enhances changes in left ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) glutamate and glutathione levels, and cortical-subcortical functional connectivity (Fc) compared with MBCT alone or NAC alone. The central hypothesis is that modulating glutamatergic output in the prefrontal cortex (PFC) and improving the cortical-subcortical functional connectivity (Fc) underlie treatment response in this population. The rationale for testing this hypothesis with a randomized controlled trial of NAC and MBCT, integrated with imaging, is that NAC is a glutamate modulator, MBCT has evidence for improving PFC-limbic Fc, both interventions have preliminary evidence for treating depression or mood symptoms have a benign safety profile. The investigators have a well-established record of conducting intervention studies integrating magnetic resonance spectroscopy (1H-MRS) and resting state functional magnetic resonance imaging (rs-fMRI) to study the neurophysiology of mood disorders. The university health center associated clinics provide the investigators access to the target population of this study. Therefore, the investigators are well positioned to investigate the neurobiological mechanisms associated with treatment response to glutamatergic modulation in mildly depressed youth. In this study, the specific aims are: Aim 1: To determine to what extent glutamate levels in the left VLPFC change in response to treatment with NAC and/or MBCT in mildly depressed youth. The investigators will utilize 1H-MRS to measure changes in the left VLPFC glutamate following eight-week treatment with NAC and/or MBCT. The investigators predict that MBCT combined with NAC will lead to greater increases in left VLPFC glutamate levels compared with either MBCT or NAC alone. Aim 2: To determine to what extent Fc within PFC-limbic circuits and within large-scale brain networks change in response to treatment with NAC and/or MBCT in mildly depressed youth. The investigators will utilize rs-fMRI to identify changes in Fc between the PFC (VLPFC, ACC) and subcortical regions, and within large scale brain networks associated with emotion and attention regulation (cingulo-opercular, fronto-parietal, and default mode networks). The investigators predict that MBCT combined with NAC will lead to greater increases in Fc compared with either MBCT or NAC alone. Exploratory Aim 3: To investigate the role of central and peripheral biomarkers of oxidative stress and inflammation in predicting response to treatment to NAC and/or MBCT for mild depression in youth. The investigators will explore the role of central glutathione and peripheral thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in predicting response to treatment to NAC and/or MBCT.

Conditions

• Mild Depression

Interventions

Type	Name	Description
DRUG	N-acetylcysteine	N-acetylcysteine 2400 mg/d
BEHAVIORAL	Mindfulness-based cognitive therapy	Mindfulness-based cognitive therapy
DRUG	Placebo	Placebo capsules
BEHAVIORAL	Sham mindfulness-based intervention	Sham mindfulness-based intervention

Timeline

• Start date: 2026-02-26
• Primary completion: 2030-03-01
• Completion: 2030-12-01
• First posted: 2026-03-11
• Last updated: 2026-03-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study