Prefrontal Glutamatergic Modulation by NAC and MBCT for Depression in Youth

NCT07464886 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: NAC+MIND - 2024-09811R01AT013115
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mild Depression

Keywords

Depression; adolescent; young adult; youth; mindfulness-based cognitive therapy; N-acetylcysteine; double-blind placebo controlled

Outcome Measures

Primary Outcomes (1)

• Glutamate levels in the left ventrolateral prefrontal cortex (VLPFC)

  Changes in glutamate levels, measured by proton spectroscopy, in the left VLPFC following 8-week treatment with NAC and/or MBCT.

  From baseline to week 8

Secondary Outcomes (1)

• Functional connectivity (Fc) within prefrontal cortex-limbic circuits and within large-scale brain networks

  From baseline to week 8

Other Outcomes (6)

• Glutathione levels in the prefrontal cortex

  From baseline to week 8

• Thiobarbituric acid reactive substances (TBARS) serum levels

  From baseline to week 8

• Malondialdehyde (MDA) serum levels

  From baseline to week 8

Study Arms (4)

NAC plus MBCT

ACTIVE COMPARATOR

N-acetylcysteine 2400 mg daily and mindfulness-based cognitive therapy over 8 weeks

Drug: N-acetylcysteine; Behavioral: Mindfulness-based cognitive therapy

Placebo plus MBCT

PLACEBO COMPARATOR

Placebo capsules and mindfulness-based cognitive therapy over 8 weeks

Behavioral: Mindfulness-based cognitive therapy; Drug: Placebo

NAC plus sham MBCT

SHAM COMPARATOR

N-acetylcysteine 2400 mg daily and sham mindfulness-based intervention over 8 weeks

Drug: N-acetylcysteine; Behavioral: Sham mindfulness-based intervention

Placebo plus sham MBCT

OTHER

Placebo capsules daily and sham mindfulness-based intervention over 8 weeks

Drug: Placebo; Behavioral: Sham mindfulness-based intervention

Interventions

N-acetylcysteine DRUG

N-acetylcysteine 2400 mg/d

Also known as: NAC; Acetylcysteine; N-acetyl-cysteine; N-acetyl-L-cysteine

NAC plus MBCT; NAC plus sham MBCT

Mindfulness-based cognitive therapy BEHAVIORAL

Mindfulness-based cognitive therapy

NAC plus MBCT; Placebo plus MBCT

Placebo DRUG

Placebo capsules

Also known as: placebo oral capsules; placebo comparator; control

Placebo plus MBCT; Placebo plus sham MBCT

Sham mindfulness-based intervention BEHAVIORAL

Sham mindfulness-based intervention

NAC plus sham MBCT; Placebo plus sham MBCT

Eligibility Criteria

• Age: 15 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• age between 15 years, 0 months to 24 years, 11 months old;
• presenting with mild depression, defined by meeting DSM-5 criteria for a current major depressive episode, mild severity, or persistent depressive disorder, or other specified depressive disorder (depressive episode with insufficient symptoms to meet criteria for a major depressive episode);
• medication-naïve or medication free for at least 5 half-lives since the last use of a psychoactive medication, with the exception of stimulants for ADHD;
• if on ADHD stimulant medication over 2 months prior to screening, willing to maintain stimulant dose constant during the study participation;
• Tanner stage greater than or equal to III;

You may not qualify if:

• significant suicidal risk, defined by suicidal ideation of type 3, 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) in the past 3 months, or any lifetime suicidal attempts;
• current major depressive episode, moderate or severe
• current or lifetime history of manic or hypomanic episodes, and/or diagnosis of bipolar disorder;
• current or lifetime history of psychotic disorders, and/or prior diagnosis of schizophrenia spectrum disorders;
• active or current substance use disorders in the last 3 months, except cannabis or alcohol use disorder, mild;
• diagnosis of autism spectrum disorder, pervasive developmental disorder, obsessive-compulsive disorder, post-traumatic stress disorders, Tourette's syndrome
• any contraindication to MRI scanning;
• pregnancy;
• history of major neurological disorder (e.g, epilepsy), or head trauma with \> 10 minutes loss of consciousness;
• intellectual disability (IQ less than or equal to 70), as determined by the Weschler Abbreviated Scale of Intelligence (WASI);
• previous participation in any mindfulness-based treatment;
• initiating psychotherapy within 2 months prior to screening, or planning to initiate psychotherapy during study participation; if on therapy, frequency and type should remain stable for 2 months prior to enrollment and during study participation;
• no current diagnosis of asthma
• history of allergic reaction to N-acetylcysteine

Sponsors & Collaborators

• University of Cincinnati: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience

Cincinnati, Ohio, 45219, United States

RECRUITING

MeSH Terms

Conditions

Depression

Interventions

Acetylcysteine; Mindfulness-Based Cognitive Therapy

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Mindfulness; Cognitive Behavioral Therapy; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Central Study Contacts

Fabiano Nery, MD, PhD

CONTACT

513 558-5035; neryfo@ucmail.uc.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: March 11, 2026
• Study Start: February 26, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (1)