Mild DepressionPhase 3NAC+MINDNCT07464886
Prefrontal Glutamatergic Modulation by NAC and MBCT for Depression in Youth
A Phase 3 study testing N-acetylcysteine and Mindfulness-based cognitive therapy in people with Mild Depression, run by University of Cincinnati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 to 24 years
- Conditions the study is for
- Mild Depression
- What is being tested?
- N-acetylcysteine and Mindfulness-based cognitive therapy
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Feb 2026to Dec 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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;
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience
Cincinnati, Ohio, 45219
Casey Moore, CCRP, 513 558-6307, casey.moore@uc.edu
About this study
Official title: Prefrontal Glutamatergic Modulation by N-acetylcysteine and Mindfulness-based Cognitive Therapy for Mild Depression in Youth
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.
Read the 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
- Being tested
- N-acetylcysteine, Mindfulness-based cognitive therapy, Placebo, Sham mindfulness-based intervention
- Keywords
- Depression, adolescent, young adult, youth, mindfulness-based cognitive therapy, N-acetylcysteine, double-blind placebo controlled
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called NAC; Acetylcysteine; N-acetyl-cysteine; N-acetyl-L-cysteine
N-acetylcysteine 2400 mg/d
Mindfulness-based cognitive therapyBehavioural
Mindfulness-based cognitive therapy
PlaceboDrug
Also called placebo oral capsules; placebo comparator; control
Placebo capsules
Sham mindfulness-based interventionBehavioural
Sham mindfulness-based intervention
| Study group | Role | What they receive |
|---|---|---|
| NAC plus MBCT | Active comparator | N-acetylcysteine 2400 mg daily and mindfulness-based cognitive therapy over 8 weeks Receives: Drug: N-acetylcysteine; Behavioral: Mindfulness-based cognitive therapy |
| Placebo plus MBCT | Placebo comparator | Placebo capsules and mindfulness-based cognitive therapy over 8 weeks Receives: 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 Receives: Drug: N-acetylcysteine; Behavioral: Sham mindfulness-based intervention |
| Placebo plus sham MBCT | Other | Placebo capsules daily and sham mindfulness-based intervention over 8 weeks Receives: Drug: Placebo; Behavioral: Sham mindfulness-based intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to week 8
Secondary outcomes (1)
Functional connectivity (Fc) within prefrontal cortex-limbic circuits and within large-scale brain networks
Changes in Fc in the prefrontal cortex (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) following treatment with NAC and/or MBCT.
Measured: From baseline to week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2026
- Study start26 Feb 2026
- Primary completionMar 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild DepressionStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Principal investigator, Fabiano Nery, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07464886
- Sponsor's protocol ID
- NAC+MIND - 2024-0981
- Other IDs
- 1R01AT013115
- Acronym
- NAC+MIND
- Status last verified
- Mar 2026
- First submitted
- 28 Jul 2025
- Last updated
- 11 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prefrontal Glutamatergic Modulation by N-acetylcysteine and Mindfulness-based Cognitive Therapy for Mild Depression in Youth
- ClinicalTrials.gov ID
- NCT07464886
- Acronym / sponsor ID
- NAC+MIND / NAC+MIND - 2024-0981
- Conditions
- Mild Depression
- Keywords
- Depression, adolescent, young adult, youth, mindfulness-based cognitive therapy, N-acetylcysteine, double-blind placebo controlled
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Study start
- 26 Feb 2026 (actual)
- Primary completion
- Mar 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 11 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NAC plus MBCT | Active comparator | Drug: N-acetylcysteine, Behavioral: Mindfulness-based cognitive therapyN-acetylcysteine 2400 mg daily and mindfulness-based cognitive therapy over 8 weeks |
| Placebo plus MBCT | Placebo comparator | Behavioral: Mindfulness-based cognitive therapy, Drug: PlaceboPlacebo capsules and mindfulness-based cognitive therapy over 8 weeks |
| NAC plus sham MBCT | Sham comparator | Drug: N-acetylcysteine, Behavioral: Sham mindfulness-based interventionN-acetylcysteine 2400 mg daily and sham mindfulness-based intervention over 8 weeks |
| Placebo plus sham MBCT | Other | Drug: Placebo, Behavioral: Sham mindfulness-based interventionPlacebo capsules daily and sham mindfulness-based intervention over 8 weeks |
Who may qualify
- Ages
- 15 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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;
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: NAC; Acetylcysteine; N-acetyl-cysteine; N-acetyl-L-cysteineN-acetylcysteine 2400 mg/d | Drug | NAC plus MBCT, NAC plus sham MBCT |
| Mindfulness-based cognitive therapyMindfulness-based cognitive therapy | Behavioural | NAC plus MBCT, Placebo plus MBCT |
| PlaceboAlso: placebo oral capsules; placebo comparator; controlPlacebo capsules | Drug | Placebo plus MBCT, Placebo plus sham MBCT |
| Sham mindfulness-based interventionSham mindfulness-based intervention | Behavioural | NAC plus sham MBCT, Placebo plus sham MBCT |
Primary outcome
Glutamate levels in the left ventrolateral prefrontal cortex (VLPFC)
Time frame: From baseline to week 8
Changes in glutamate levels, measured by proton spectroscopy, in the left VLPFC following 8-week treatment with NAC and/or MBCT.
1 secondary outcome
Functional connectivity (Fc) within prefrontal cortex-limbic circuits and within large-scale brain networks
Time frame: From baseline to week 8
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing N-acetylcysteine and Mindfulness-based cognitive therapy in people with Mild Depression, run by University of Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fabiano Nery, MD, PhD (513 558-5035, neryfo@ucmail.uc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glutamate levels in the left ventrolateral prefrontal cortex (VLPFC) (time frame: From baseline to week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2026.