mGluR5 and sleep-focused CBT for depression

Mechanistic Clinical Trial Evaluating the Role of the Metabotropic Glutamate Receptor Subtype 5 (mGluR5) in the Antidepressant Mechanism of Cognitive Behavioral Therapy for Insomnia (CBT-I)

This trial will test whether an online sleep program (CBT-I) changes brain mGluR5 levels and improves sleep and depression in adults with moderate-to-severe major depressive disorder.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Stony Brook University (other)
• Locations: 1 site (Stony Brook, New York)
• Trial ID: NCT07076342 on ClinicalTrials.gov

What this trial studies

This is a mechanistic, interventional Phase 4 trial in adults with a current major depressive episode and significant insomnia. Participants will complete baseline and post-treatment PET imaging using [11C]ABP688 to quantify hippocampal mGluR5 density and will have overnight polysomnography to measure sleep latency. CBT-I will be delivered remotely via the SHUTi online program, and changes in mGluR5 and sleep will be compared before and after the intervention. Key exclusions include current effective antidepressant use, psychosis history, recent substance dependence, nicotine use within one year, other sleep disorders, and medications known to affect glutamate.

Who should consider this trial

Good fit: Adults (≥18) with current major depressive disorder (MADRS >29), insomnia with sleep latencies within the study range, good physical health, and not taking effective antidepressants or glutamate-affecting medications.

Not a fit: People with psychosis, recent substance dependence, other primary sleep disorders (e.g., sleep apnea), recent nicotine use, or on medications that affect glutamate are excluded and would not be expected to benefit from participation.

Why it matters

Potential benefit: If successful, the trial could show that improving sleep with CBT-I reduces mGluR5 and depressive symptoms, supporting a non-drug pathway to treat depression.

How similar studies have performed: Previous trials show CBT-I can reduce depressive symptoms similarly to antidepressants, but using PET to link those effects to mGluR5 downregulation is a novel, less-tested approach.

Eligibility criteria

Inclusion Criteria:

* capacity to provide informed consent,
* at least 18 years of age
* good physical health and absence of significant medical conditions,
* diagnosis of major depressive disorder (MDD) with current major depressive episode as per DSM-5 criteria
* Montgomery-Åsberg Depression Rating Scale (MADRS) score \> 29 (at least moderate depression),
* uniform range of sleep latencies up to 128 minutes.

Exclusion Criteria:

* currently taking effective antidepressants,
* lifetime history of psychosis,
* drug or alcohol dependence in the last 6 months or abuse in the last 2 months
* unstable medical condition (i.e., condition not adequately stabilized for ≥ 3 months)
* nicotine use within 1 year
* currently on medication known to affect glutamate,
* sleep disorders, other than insomnia, such as sleep apnea,
* recent (within 1 year) regular night shift work (or rotating shift work) or recent (within 3 months) travel across more than one time zone, or plans for this work or travel during the study period,
* use of medication or substances that affect sleep, for example, ingestion of more \> 600 mg of caffeine per day,
* PET or MRI contraindications, including pregnancy or currently breastfeeding

Where this trial is running

Stony Brook, New York

• Stony Brook University: Dept of Psychiatry — Stony Brook, New York, United States (RECRUITING)

Study contacts

• Study coordinator: Wendy Zhang

Conditions: Major Depressive Disorder, Cognitive Behavioral Therapy, CBT-I, Cognitive Behavioral Therapy &amp, Insomnia