Combining N-acetylcysteine and mindfulness-based cognitive therapy to target prefrontal glutamate in mildly depressed youth

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This randomized Phase 3 trial compares combined NAC plus MBCT versus NAC alone, MBCT alone, and placebo with a sham mindfulness intervention in mildly depressed participants aged 15 to 24. Treatment effects will be linked to neurobiological measures using proton magnetic resonance spectroscopy (1H-MRS) to quantify glutamate and glutathione in left VLPFC and ACC, and resting-state fMRI to measure cortical-subcortical functional connectivity. Participants are medication-naïve or medication-free (with specific exceptions for stable ADHD stimulants) and will attend in-person therapy and imaging visits at the study site. The study aims to determine whether changes in glutamatergic signaling and PFC-limbic connectivity underlie clinical improvement in this population.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. age between 15 years, 0 months to 24 years, 11 months old;
2. 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);
3. 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;
4. if on ADHD stimulant medication over 2 months prior to screening, willing to maintain stimulant dose constant during the study participation;
5. Tanner stage greater than or equal to III;

Exclusion Criteria:

1. 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;
2. current major depressive episode, moderate or severe
3. current or lifetime history of manic or hypomanic episodes, and/or diagnosis of bipolar disorder;
4. current or lifetime history of psychotic disorders, and/or prior diagnosis of schizophrenia spectrum disorders;
5. active or current substance use disorders in the last 3 months, except cannabis or alcohol use disorder, mild;
6. diagnosis of autism spectrum disorder, pervasive developmental disorder, obsessive-compulsive disorder, post-traumatic stress disorders, Tourette's syndrome
7. any contraindication to MRI scanning;
8. pregnancy;
9. history of major neurological disorder (e.g, epilepsy), or head trauma with \> 10 minutes loss of consciousness;
10. intellectual disability (IQ less than or equal to 70), as determined by the Weschler Abbreviated Scale of Intelligence (WASI);
11. previous participation in any mindfulness-based treatment;
12. 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;
13. no current diagnosis of asthma
14. history of allergic reaction to N-acetylcysteine

Where it's running

• University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience
  Cincinnati, Ohio, United States Recruiting

Study contacts

• Study coordinator: Fabiano Nery, MD, PhD
• Email: neryfo@ucmail.uc.edu
• Phone: 513 558-5035

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.